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Formulation approaches for sustained release dosage forms: A review
Abstract
Over the past 30 years, as the expense and complications involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, greater attention has been focused on development of sustained or controlled release drug delivery systems (DDS). For many disease states, a substantial number of therapeutically effective compounds already exist. The effectiveness of these drugs is often limited by side effects or necessity to administer the compound in an ethical setting. The goal in designing sustained drug delivery is to reduce the frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required or providing uniform drug delivery. The design of oral sustained release DDS depends on various factors such as, physicochemical properties of drug, type of delivery system, disease being treated, and patient condition, and treatment duration, presence of food, gastrointestinal motility, and co-administration of other drugs. © 2015, Asian Journal of Pharmaceutical and Clinical Research. All Rights Reserved.
... Arbitrary therapeutic range of different dosage form in blood [14] They are the class of medications or other biologically active material that release a drug from the delivery mechanism in a predictable, planned and longer-lasting manner than usual [13]. Zero-order release is used in this system, which is independent of SRDDS adheres to first order release, whereas initial drug concentration is followed. ...
... Drugs from in which one portion may release immediately and remaining release discrete a fraction of time combined into a single dosage form are dosed repeatedly and intermittently in delayed release systems [13]. ...
... These are the alternate SR systems, where each dose of the medication is released at regular intervals and numerous doses are contained within the dosage form [13]. ...
Controlled Drug Delivery Systems (CDDS) represent a significant advancement in pharmaceutical technology, designed to deliver therapeutic agents in a controlled and sustained manner over an extended period. These systems aim to optimize the drug's efficacy by maintaining therapeutic drug levels in the body, reducing side effects, and enhancing patient compliance. CDDS can be classified into various categories, including polymeric, liposomal, and nanoparticle-based systems, each offering unique benefits. Polymeric systems, for example, allow for the precise release of drugs through diffusion, degradation, or swelling mechanisms. Drugs can be targeted to certain tissues with the use of liposomes and nanoparticles, increasing the therapeutic index while lowering systemic exposure. To further improve the accuracy of drug administration, CDDS can also be made to react to environmental stimuli like pH, temperature, or electromagnetic fields. The creation of CDDS has been the subject of extensive research in recent decades in order to solve issues such patient adherence, drug stability, and bioavailability. With the development of new materials and technology, CDDS remains a promising treatment option for cancer, chronic diseases, and other complex medical problems, offering more individualized and efficient therapeutic alternatives.
... As shown in fig. 1(a-b) a graph of absorbance vs. concentration was generated, indicating that Beer's law was followed in the concentration range of 10 to 80 µg/ml [31]. ...
... There was no significant interaction between various rational combinations combining a physical mixture of drug with polymers (i.e., sodium alginate and HPMC K4M) and optimised microspheres, as shown in fig. 2 (a-c) [30,31]. ...
... Microspheres of particle sizes ranged from 389.43 to 835.63 µm. Factors including polymer concentration, cross-linking agent amount, and stirring duration all influenced size distribution variability between batches [31]. ...
Objective: The study is to formulate the enalapril maleate-loaded mucoadhesive microspheres with varied compositions of selected polymers for developing the oral controlled release formulations prepared by ionic gelation method and optimization through central composite design. Methods: Systematic optimization of microspheres was accomplished by the central composite design and characterized for particle size, entrapment efficiency, in vitro drug release and ex vivo mucoadhesion strength, which indicated that microspheres were a consequence to be spherical and free-flowing in nature. The microspheres exhibited high drug entrapment efficiency and in vitro drug release in a sustained manner, which was considered to be dependent on the concentration of rate-controlling polymers. The microspheres are showed 389.2 to 850 µm particle size and 22.36 to 85.22 % encapsulation efficiency. In vitro studies indicated optimized formulation showed 89.26% drug release after 12h and reduced blood pressure effectively. Results: The pharmacokinetic parameters were evaluated with Cmax of 75.39 µg/ml, tmax of 8h, and AUC of 53.55 µg/hr/ml, elimination rate constant of 0.0392 and t1/2 of 10h. The stability studies were conducted for 3 mo under various conditions and identified no significant deviations in selected key quality attributes. Conclusion: The formulated mucoadhesive microspheres of enalapril maleate tend to reduce the blood pressure in the animal model, with the novel drug delivery approach in the efficient management of hypertension.
... It has been found to be an effective manufacturing technique for enhancing solubility and bioavailability for BCS class II and class IV drugs as evident by several marketed products based on HME technology [1][2][3]. The applications of HME process have now been extended for the development of sustained-release formulations [4,5], controlled-release formulations [6,7], *Address correspondence to this author at the National Institute of Pharmaceutical Education and Research -Ahmedabad (NIPER-A) An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar -382355, Gujarat, India; Tel: +91 79 66745555, +91 79 66745501; Fax: +91 79 66745560; E-mail: derajram@niperahm.res.in ...
... This molten mass further gets uniformly mixed before reaching the die and is molded into desired shapes while coming out of the orifice [66,67]. The downstream auxiliary equipment provided for cooling, cutting, and collecting the processed materials give the final shape to the product [4]. The temperature of the barrel is usually optimized and controlled to maintain the desired temperature range and is a material characteristic of T g, as discussed previously. ...
... The temperature of the barrel is usually optimized and controlled to maintain the desired temperature range and is a material characteristic of T g, as discussed previously. The single screw extruders are mainly for melting and passing the polymers to extrude into continual shapes, while twinscrew extruders are utilized for melt-mixing of polymers with additional components (pigments, fillers, reinforcers, and drugs) and devolatilization [4]. Hence, twin-screw extruders are usually preferred in pharmaceutical industries owing to homogenous mixing, which, in turn, can lead to an improved as well as consistent dissolution enhancement of poorly water-soluble drugs. ...
The Hot Melt Extrusion (HME) technique has shown tremendous potential in transforming highly hydrophobic crystalline drug substances into amorphous solids without using solvents. This review explores in detail the general considerations involved in the process of HME, its applications and advances.
... It has been found to be an effective manufacturing technique for enhancing solubility and bioavailability for BCS class II and class IV drugs as evident by several marketed products based on HME technology [1][2][3]. The applications of HME process have now been extended for the development of sustained-release formulations [4,5], controlled-release formulations [6,7], *Address correspondence to this author at the National Institute of Pharmaceutical Education and Research -Ahmedabad (NIPER-A) An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Opp. Airforce Station, Palaj, Gandhinagar -382355, Gujarat, India; Tel: +91 79 66745555, +91 79 66745501; Fax: +91 79 66745560; E-mail: derajram@niperahm.res.in ...
... This molten mass further gets uniformly mixed before reaching the die and is molded into desired shapes while coming out of the orifice [66,67]. The downstream auxiliary equipment provided for cooling, cutting, and collecting the processed materials give the final shape to the product [4]. The temperature of the barrel is usually optimized and controlled to maintain the desired temperature range and is a material characteristic of T g, as discussed previously. ...
... The temperature of the barrel is usually optimized and controlled to maintain the desired temperature range and is a material characteristic of T g, as discussed previously. The single screw extruders are mainly for melting and passing the polymers to extrude into continual shapes, while twinscrew extruders are utilized for melt-mixing of polymers with additional components (pigments, fillers, reinforcers, and drugs) and devolatilization [4]. Hence, twin-screw extruders are usually preferred in pharmaceutical industries owing to homogenous mixing, which, in turn, can lead to an improved as well as consistent dissolution enhancement of poorly water-soluble drugs. ...
Background
The Hot Melt Extrusion (HME) technique has shown tremendous potential in transforming highly hydrophobic crystalline drug substances into amorphous solids without using solvents. This review explores in detail the general considerations involved in the process of HME, its applications and advances.
Objective
The present review examines the physicochemical properties of polymers pertinent to the HME process. Theoretical approaches for the screening of polymers are highlighted as a part of successful HME processed drug products. The critical quality attributes associated with the process of HME are also discussed in this review. HME plays a significant role in the dosage form design, and the same has been mentioned with suitable examples. The role of HME in developing several sustained release formulations, films, and implants is described along with the research carried out in a similar domain.
Methods
The method includes the collection of data from different search engines like PubMed, ScienceDirect, and SciFinder to get coverage of relevant literature for accumulating appropriate information regarding HME, its importance in pharmaceutical product development, and advanced applications.
Results
HME is known to have advanced pharmaceutical applications in the domains related to 3D printing, nanotechnology, and PAT technology. HME-based technologies explored using Design-ofExperiments also lead to the systematic development of pharmaceutical formulations.
Conclusion
HME remains an adaptable and differentiated technique for overall formulation development.
... The continuing need to optimize drug therapy has generated in recent years the development of new modified transport systems for drug release based on raw materials that influence the release characteristics and absorption of the active substance. In recent years, polysaccharides have increasingly began to be used as matrix materials to obtain particulate systems capable of delivering controlled and target drug release [1,2]. Unlike conventional therapy, which involves the immediate release of the drug causing a poor control of the concentration of the substance in plasma by increasing sometimes its concentration above the toxic level, then the concentration falls below the therapeutic limit, these new systems are designed to transport and release the therapeutic agent in a controlled manner [3]. ...
... Unlike conventional therapy, which involves the immediate release of the drug causing a poor control of the concentration of the substance in plasma by increasing sometimes its concentration above the toxic level, then the concentration falls below the therapeutic limit, these new systems are designed to transport and release the therapeutic agent in a controlled manner [3]. The biopharmaceutical benefits of modified-release particulate systems based on natural polysaccharides can be quantified as follows: controlled release and optimization of the therapeutic effect of the drug substance, reducing adverse effects, lowering production costs, increasing patient compliance by modifying posology and, last but not least, improving the quality of patients' lives [2,4]. A major application of natural polysaccharides is their use as gelling/cryogel forming agents containing a large amount of water in the three-dimensional structure, being widely used in biomedical, tissue engineering and controlled release of drugs for local or systemic effect [5,6]. ...
... The results of EM loading and EE were calculated using equations (2) and (3). ...
... It has focused on stereo-complex materials, their interactions, and cross-linking through physical interactions [2]. Yana and his partners worked on collagen and shark cartilage tissues to develop a novel dressing that effectively decreased the healing burn [7]. Natural and synthetic hydrogels are used extensively in tissue engineering. ...
... Hydrogels offer a variety of pharmaceutical, medical, and clinical applications like tissue regeneration, diagnostic applications, mucoadhesive potentials, etc. Hydrogels in literature are formulated in different shapes like nano and micro-sized particles, hydrogel membranes, beads, matrics, etc. [7][8][9][10][11], depending upon the required use. ...
This book chapter give an overview of natural and synthetic polymeric moieties consumed for developing hydrogels and their types. Different properties of nanogels are the advancement of hydrogels characterized by nano-size range, stimuli-responsive swelling, and release. Stimuli responsiveness is imparted by the presence of a suitable monomer. A number of polymerization approaches are presented in the literature that are employed to prepare such networks. These systems are elastic, rubbery, nontoxic, and biocompatible and offer prolonged release of the drugs without chances of dose dumping. These types of networks have potential pharmaceutical, agricultural, food, and biotechnological applications in terms of controlled, prolonged, and targeted drug delivery, solubility enhancements, stimuli-dependent intelligent drug delivery, such as contact lenses, wound healing, etc. In the current chapter, we have tried to introduce hydrogels and microgels, their different types, the variety of polymers used to develop such carrier systems, approaches to develop such drug delivery systems, and their utilization in various sectors in addition to the pharmaceutical sector.
... Its best fit values are 0.092 h −1 and 0.056 h −1 for 37 and 43 • C, respectively. Note that in a first order release profile the process is directly proportional to the drug concentration that is involved in the process, whereas in a zeroth-order release the drug is released at a constant rate, leading to the best control of plasma concentration and offering several advantages, including improved patient compliance and reduction in the frequency of drug administration [80,81]. This feature is also a positive result of using hyperthermia in combination with drug release. ...
... Its best fit values are 0.092 h −1 and 0.056 h −1 for 37 and 43 °C, respectively. Note that in a first order release profile the process is directly proportional to the drug concentration that is involved in the process, whereas in a zeroth-order release the drug is released at a constant rate, leading to the best control of plasma concentration and offering several advantages, including improved patient compliance and reduction in the frequency of drug administration [80,81]. This feature is also a positive result of using hyperthermia in combination with drug release. ...
In this work a combined, multifunctional platform, which was devised for the simultaneous application of magnetic hyperthermia and the delivery of the antitumor drug gemcitabine, is described and tested in vitro. The system consists of magnetite particles embedded in a polymer envelope, designed to make them biocompatible, thanks to the presence of poly (ethylene glycol) in the polymer shell. The commercial particles, after thorough cleaning, are provided with carboxyl terminal groups, so that at physiological pH they present negative surface charge. This was proved by electrophoresis, and makes it possible to electrostatically adsorb gemcitabine hydrochloride, which is the active drug of the resulting nanostructure. Both electrophoresis and infrared spectroscopy are used to confirm the adsorption of the drug. The gemcitabine-loaded particles are tested regarding their ability to release it while heating the surroundings by magnetic hyperthermia, in principle their chances as antitumor agents. The release, with first-order kinetics, is found to be faster when carried out in a thermostated bath at 43 °C than at 37 °C, as expected. But, the main result of this investigation is that while the particles retain their hyperthermia response, with reasonably high heating power, they release the drug faster and with zeroth-order kinetics when they are maintained at 43 °C under the action of the alternating magnetic field used for hyperthermia.
... Altered density formulation Levodopa and benserazide. [5] MARKETD PRODUCTS LIST ...
... Hydrogels are under consideration among other novel drug delivery systems. These polymeric networks reduce the limitations of conventional dosage forms and also support a more stable, appropriate, and biocompatible drug delivery system (Karna et al., 2015;Khan et al., 2016). Hydrogels are three-dimensional polymeric networks (Chopra et al., 2022b) that have the capability to absorb water without being dissolved (Chopra et al., 2022a). ...
Introduction: The objective of current project was to formulate a system for controlled delivery of Tramadol HCl (TRD), an opioid analgesic used in the treatment of moderate to severe pain.
Methods: For this purpose, a pH responsive AvT-co-poly hydrogel network was formulated through free radical polymerization by incorporating natural polymers i.e., aloe vera gel and tamarind gum, monomer and crosslinker. Formulated hydrogels were loaded with Tramadol HCl (TRD) and evaluated for percent drug loading, sol-gel fraction, dynamic and equilibrium swelling, morphological characteristics, structural features and in-vitro release of Tramadol HCl.
Results and Discussions: Hydrogels were proved to be pH sensitive as remarkable dynamic swelling response ranging within 2.94g/g-10.81g/g was noticed at pH 7.4 as compared to pH 1.2. Percent drug loading was in the range of 70.28%-90.64% for all formulations. Thermal stability and compatibility of hydrogel components were validated by DSC analysis and FTIR spectroscopy. Controlled release pattern of Tramadol HCl from the polymeric network was confirmed as maximum release of 92.22% was observed for over a period of 24 hours at pH 7.4. Moreover, oral toxicity studies were also conducted in rabbits to investigate the safety of hydrogels. No evidence of any toxicity, lesions and degeneration was reported, confirming the biocompatibility and safety of grafted system.
... The goal of designing a sustained release drug delivery system is to minimize a medicine's dose, boost its effectiveness by targeting a specific site of action, or provide consistent drug administration. So, a sustained-release (SR) dosage form is one that continuously delivers one or more medications in a planned manner over a set period, either systemically or to a specific target [22]. ...
Background: A tablet is a solid dosage form containing active pharmaceutical ingredients (API) and various excipients. Different procedures, such as direct compression of powder mixtures, dry and wet granulation technologies, are used to create distinct types of tablets. Tablet development is aided by technological advancements in the form of modified-release tablets.
Objective: The modified release dosage form can be manufactured to obtain a specific pharmaceutical profile, the specific site of action, and reduce the number of dose administrations using a variety of coating technologies. For modified release drug delivery, various sorts of patents are explored. The review's primary goal is to provide information on modified release formulations, formulation methodologies, current active patents based on modified release, and tablet coating technologies.
Conclusion: The tablet is a more considerable dose form. Modified release drug administration has largely supplanted traditional tablet drug delivery technologies in recent years. Chrono pharmaceutical drug delivery can also involve modified drug delivery. Modified release tablets are used to boost the therapeutic impact of a medicine by targeting the location of action on the illness condition. Modified-release tablets are very handy, easy to create, cost-effective, and do not require high-cost equipment, and they are gaining in popularity these days. Patents for modified-release tablet dosage formulations that are currently active were also discussed.
... These have made smart systems of utmost importance. The latter reduces the fluctuation in concentration and their toxicity while enhancing the therapeutic efficacy [52]. The following are essential factors to be considered when designing nanomaterials as drug carriers: (i) they should be biocompatible and biodegradable (ii) possess good stability in physiological conditions, (iii) have high drug loading capacity, and (iv) be less toxic. ...
There has been an increasing number of studies in magnetic nanoparticles with auspicious applications in medicine. Among the oxides of magnetic nanoparticles, iron oxide has emerged as an indispensable tool in nanotechnology, particularly bio-nanotechnology. This is attributed to its exceptional properties such as size, shape, magnetism, and biocompatibility. In this review, iron oxide nanoparticles were exploited in different model organisms ranging from prokaryotes to eukaryotes, elucidating their cellular functions relative to their antibacterial activity, drug delivery, and toxicity.
... Properties of sustained release formulation [2] detailing of sustained release drug conveyance frameworks, consider the a few criteria, for example, the course of organization, kind of drug conveyance framework, what ailment to be dealt with, the patient, the length of treatment and the normal for the drug those previously mentioned factor ought to be considered. The pharmaceutical enthusiasm to inquire about researcher for planning of the conveyance framework the accompanying properties could be considered in the improvement of dose structure. ...
Sustained release tablets of Diclofenac Sodium was prepared by using HPMC and Ethyl cellulose. The Evaluation of tablets is involved the Preformulation studies such as compressibility index, bulk density, angle of repose, and physical characteristics like hardness, weight variation friability, and drug content. In-vitro release of drug was performed in Phosphate Buffer System having pH 7.2 for 10 hours. All the physical characters of the fabricated tablet were within acceptable limits. Dissolution profile of Diclofenac sodium from matrix tablets prepared using different polymers were indicated an increase in the polymer ratio retarded the drug release to a greater extent.
... To overcome the drawbacks of the conventional drug delivery system in recent times, the current research area is to develop modified dosage systems to give a more stable and economical dosage form. Among different drug delivery systems, hydrogels are under consideration, which not only decreases the demerits of the conventional dosage form but also provides a stable, more convenient, and biocompatible drug delivery system [5,6]. Hydrogels have gain attention from the past years due to their extensive applications in medical, biological, and pharmaceutical disciplines [7,8]. ...
... To overcome the drawbacks of the conventional drug delivery system in recent times, the current research area is to develop modified dosage systems to give a more stable and economical dosage form. Among different drug delivery systems, hydrogels are under consideration, which not only decreases the demerits of the conventional dosage form but also provides a stable, more convenient, and biocompatible drug delivery system [5,6]. Hydrogels have gain attention from the past years due to their extensive applications in medical, biological, and pharmaceutical disciplines [7,8]. ...
This study investigated the use of Artemisia vulgaris L. seed mucilage as a new excipient for sustained delivery of Vildagliptin. Copolymeric carrier of A. vulgaris seed mucilage-co-AAm was devised by using acrylamide (AAm) as a monomer, methylene-bis-acrylamide (MBA) as a crosslinker, and potassium persulfate (KPS) as an initiator through free radical polymerization. Different formulations of A. vulgaris-co-AAm were devised by varying contents of polymer, monomer, crosslinking agent, initiator, and reaction temperature. Copolymeric structures were characterized through XRD analysis, Fourier transform infrared (FTIR) spectroscopy, TGA and DSC analysis, and scanning electron microscopy. Porosity, gel fraction, and Vildagliptin loading capacity of copolymers were also established. Swelling and in vitro drug release studies were conducted. XRD evaluation showed the alteration of the crystalline structure of Vildagliptin into an amorphous form. FTIR analysis confirmed the successful grafting of AAm to A. vulgaris seed mucilage backbone. Porosity was increased with increasing polymer concentration and reaction temperature while it was decreased with an increasing amount of AAm, MBA, and KPS. Gel content was decreased with increasing polymer concentration and reaction temperature while it was increased with an increasing amount of AAm, MBA, and KPS. Acute oral toxicity of copolymeric network was done in animal models to evaluate the safety. Copolymers showed the same swelling behavior at all pH 1.2, 4.5, 6.8, and 7.4. Vildagliptin release from copolymer showed a cumulative trend by increasing polymer content and reaction temperature, while a declining trend was observed with increasing contents of monomer, crosslinking agent, and initiator. Sustained release of Vildagliptin was observed from copolymers and release followed the Korsmeyer-Peppas model. From the acute oral toxicity studies, it is evident that newly synthesized copolymeric carriers are potentially safe for eyes, skin, and vital organs.
1. Introduction
Naturapolyceutics is based on interdisciplinary approaches that combine natural polymer and pharmaceutics for advancement in drug delivery design [1]. Since the primal epoch, plants frisked a vibrant character in human daily life from purposeful food to medication [2]. Plant-derivative excipients are constant applicants, which display a spirited part in pharmaceutical product development. Furthermore, the marvelous direction of formulation scientists towards the development of plant instigated excipient offerings a new edge to ascertain, extract, and refine such compounds. Plant polysaccharides, such as gums and mucilages, are commonly used in pharmaceutical, biomedical, and cosmetic industries. Moreover, seed coats of several plants extrude mucilage on potential connection with water [3]. This mucilage comprises complex polysaccharides, which are plentiful with a high degree of biocompatibility, biodegradability, and ability to imitate the natural extracellular matrix (ECM) microenvironment. Due to their diverse nature, these functional materials are in great demand to ripen sustained/controlled/targeted formulations in design and drug delivery [4].
To overcome the drawbacks of the conventional drug delivery system in recent times, the current research area is to develop modified dosage systems to give a more stable and economical dosage form. Among different drug delivery systems, hydrogels are under consideration, which not only decreases the demerits of the conventional dosage form but also provides a stable, more convenient, and biocompatible drug delivery system [5, 6]. Hydrogels have gain attention from the past years due to their extensive applications in medical, biological, and pharmaceutical disciplines [7, 8].
Hydrogels are the copolymeric networks that can swell and keep water within its polymeric network without dissolving in water [7]. Graft copolymers represent surplus benefits, especially stimuli-responsive polymers, such as higher acid-base and thermal resistance and lower crystallinity of natural polymers. Graft copolymers are prepared by first creating free radicals on the biopolymer backbone and then permitting these radicals to function as macroinitiators [9]. As compared to conventional drug delivery systems, hydrogels have prolonged and sustained action. They are biocompatible, biodegradable and provide site-specific drug delivery. This results in improved patient compliance due to reduced frequency of dosing and side effects [8, 10].
A. vulgaris L., commonly known as mugwort, belongs to family Compositae and is native to Europe, Asia, and northern Africa. Artemisia species are used throughout the world for their different kinds of medicinal properties, e.g., anti-inflammatory, antimicrobial, antioxidant, and antimalarial. Artemisia vulgaris seed mucilage, which shows amazing swelling in water, shows stimuli-responsiveness in different physiological conditions, solvents, and electrolytes [11].
Acrylamide is one of the favourite choices due to its excellent compatibility, ease of preparation, noncarcinogenicity, low cost, biocompatibility, and biodegradability [12].
The integral parts of copolymeric carrier synthesis are polymer, monomer, crosslinking agent, and initiator. The swelling behavior of hydrogels depends upon the nature of the polymer, monomer, initiator, and crosslinking agent as well as their concentrations and reaction temperature. The applications of hydrogels mainly depend upon the swelling behavior of the polymeric network of the hydrogel. These formulation parameters are used to alter the swelling behavior of hydrogels to modify the drug release. Extensive studies have been reported to modify swelling properties of crosslinked hydrogels by varying the formulation parameters such as the concentration of polymer, monomer, crosslinking agent, initiator, and various reaction temperatures [13–18].
Vildagliptin is an effective, selective, and orally dynamic dipeptidyl peptidase-4 (DPP-4) inhibitor, which inhibits inactivation of incretion hormones by inhibiting DPP-4 [19]. Its biological half-life is 1 to 3 hours as a result; it entails recurrent management to retain optimum plasma drug level. For the mentioned purpose, a sustained release drug delivery system improves patient compliance by dropping frequency of dosing. Thus, there is a strong clinical prerequisite and market prospective for a dosage form that will provide Vildagliptin in a sustained fashion to a patient demanding therapy. So it could be a potential candidate for safe and effective sustained drug delivery from an ideal dosage form for the treatment of type II diabetes [20].
The present work was undertaken to prepare hydrogels from Artemisia vulgaris mucilage and acrylamide blend by the application of free radical polymerization. The purpose of the current study was to evaluate mucilage obtained from Artemisia vulgaris as a new excipient of natural origin for producing smart drug delivery systems such as graft copolymer.
2. Materials and Methods
2.1. Materials
Seeds of Artemisia vulgaris were procured from Seed Needs, LLC. Acrylamide, potassium persulfate, sodium hydroxide, and potassium dihydrogen phosphate were purchased from Sigma-Aldrich, Germany. Methylene-bis-acrylamide was purchased from Fluka, Switzerland. Hydrochloric acid and absolute ethanol were purchased from Riedel-de Haen, Germany. The drug Vildagliptin (99.5% purity) was obtained from M/S Fuxin Long Rui Pharmaceutical Co. Ltd. Distilled water was obtained from the distillation unit of the University of Sargodha. All other chemicals used in this study were of analytical grade.
2.2. Extraction of Artemisia vulgaris Seed Mucilage
The Artemisia vulgaris mucilage was obtained by a hot water extraction method. Extraneous materials were removed by picking and sieving of seeds (200 g). Uncontaminated seeds were soaked in distilled water (1 : 9 ratio) at room temperature for 48 hours. Swollen seeds of Artemisia vulgaris were passed by 40 mesh sieve later heated at 80°C for 30 minutes. The thick exudate was separated by nylon mesh. Defatted mucilage was obtained by n-Hexane (≥98.0% purity, Sigma-Aldrich, Germany) treatment; the resultant was later washed thoroughly with distilled water (repeated thrice) to collect pure mucilage. Dried Artemisia vulgaris mucilage was triturated to obtain even powder of extract and stored in vacuum desiccators [21].
2.3. Determination of Purity of Artemisia vulgaris Seed Mucilage
Aqueous extract was prepared by dissolving Artemisia vulgaris Seed Mucilage powder in distilled water. Molisch’s reagent and sulphuric acid were used to identify the presence of carbohydrates. Molisch’s reagent was added in the aqueous extract of mucilage; then sulphuric acid was added (Malviya et al. [22]). Amino acid presence in extracted powder was checked by dissolving aqueous extract with Ninhydrin reagent (Farooq et al. [23]).
2.4. Synthesis of Artemisia vulgaris-AAm Copolymers
AV seed mucilage was suspended in distilled water with constant stirring at 70°C. KPS was added to it to generate free radicals. A solution of AAm (monomer) and MBA was prepared and transferred to the reaction mixture. The reaction mixture was placed in a water bath for polymerization with continuous rise in temperature from 45 to 70°C by 10°C/h. The temperature was kept at 70°C to complete the reaction. Copolymers attained were cut into discs of 0.5 cm. Ethanol and water (30 : 70) were used to remove an unreacted monomer followed by drying in an oven at 50°C. These discs were kept in a desiccator till further use. A similar method was followed to prepare copolymers at room temperature as a reaction temperature [24].
The composition of all formulations with varying contents is summarized in Table 1.
Formulation code
Polymer (g/100 g)
Monomer (g/100 g)
Initiator (g/100 g)
Crosslinker (g/100 g)
Temperature
P1
1
15
0.4
0.4
70°C
P2
1.5
15
0.4
0.4
70°C
P3
2.0
15
0.4
0.4
70°C
M1
2.0
10
0.4
0.4
70°C
M2
2.0
20
0.4
0.4
70°C
M3
2.0
25
0.4
0.4
70°C
M4
2.0
30
0.4
0.4
70°C
C1
2.0
15
0.4
0.5
70°C
C2
2.0
15
0.4
0.75
70°C
C3
2.0
15
0.4
1.0
70°C
I1
2.0
15
0.5
0.4
70°C
I2
2.0
15
0.6
0.4
70°C
I3
2.0
15
0.7
0.4
70°C
T1
2.0
15
0.4
0.4
70°C
R1
2.0
15
0.4
0.4
Room temperature
... Central composite design (CCD) was used to describe the relationship between the independent variables and the responses as well as to determine the drug loading parameters for drug loaded micro-granules to reduce the number of trials which necessary to attain maximum numbers of information on product properties, and the screening was performed applying a 3 2 CCD. [13] Tab 3. List of 3 2 Central composite design. ...
The work investigates the minimization of initial burst in alginate hydrogel beads by ionotropic gelation method. The design of effective and safe drug delivery systems has become an integral part for the development and formulating of new medicines. So, research continuously keeps on searching for new ways to deliver drugs over a long period of time or for a well-controlled release profile, to minimizing the loss of drug, to reduce the side effect. The beads were prepared by using sodium alginate coated with chitosan, containing Metformin hydrochloride by ionotropic gelation using central composite design. The influence of various formulation factors such as In-vitro drug release, drug entrapment efficiency, swelling study, bead size and micromeritic properties, was investigated. These were also characterized by Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analysis. Metformin hydrochloride containing hydrogel beads were in the size range of 1.84±0.02 to 2.00±0.15 mm. Metformin hydrochloride loading amount, concentration of chitosan, polymer concentration and cross-linking agent seemed to affect the values of particle size. It was found that the particle size decreased significantly by increasing sodium alginate concentration. The drug entrapment efficiency was found in the range of 86.14±1.85 to 93±1% and the drug release were found at 8 h in the range 70±0.49% to 90.84±0.94%. The release pattern observed was a biphasic, characterized by an initial burst effect followed by slow release. No significant change was found in the drug content of drug-loaded beads, stored at room temperature and 40°C after 60 days of study.
... This may be attributed to the functional coating system and less or non-porous matrix structure of Ranexa ® tablets. In spite of the fact that controlled release drug delivery systems exhibit a constant concentration (plateau) and zero-order release kinetics, in sustained and extended-release drug delivery systems, the drug release behavior would be over an extended period of time, and thereby zeroorder release kinetics would not be attained, except in the case of osmotic-controlled release oral delivery systems [12,13,41]. ...
Objective: Ranolazine (RZ), antianginal drug indicated for the treatment of chronic stable angina pectoris, was formulated into sustained-release matrix tablets and optimized to improve patient compliance and achieve controlled release over a certain period.
Methods: Different formulations were prepared by wet-and melt-granulation techniques. Excipients at different ratios as Eudragit ® L100-55, Methocel ™ E5, Avicel ® PH-101, and carnauba wax powder were used to develop a ternary polymeric matrix system for the controlled delivery of RZ. The prepared formulations were subjected to granulometric and characteristic studies. Comparative dissolution and release kinetic studies of the selected formulation and the reference product, Ranexa ® extended-release film-coated tablets, Gilead Sciences, Inc., USA, were further carried out to ensure product similarity.
Results: The optimum pH-dependent to pH-independent polymers ratio was 1:1.3 (w/w). Extragranular carnauba wax in a concentration of 32.50 mg/tablet (2.50 gm% w/w) was the key excipient in controlling drug release kinetics by forming waxy matrix granules which prevent rapid dissolution. Modulation of the microenvironmental pH using a potent alkalinizing agent was very effective for controlling drug release patterns in different dissolution media from pH 1.2-6.8.
Conclusion: The release of RZ from the matrix tablets was controlled for a period of 24 h, and thereby expected to provide patient compliance with minimal side effects.
... However, these systems are associated with several limitations, e.g. stability issues, toxicity due to dose dumping, gastric irritation, instability at acidic pH, high cost and less dose adjustment [2]. To overcome these problems, the focus has been drawn towards nanotechnological approaches, where the release of the drug can be controlled in a more precise manner. ...
Purpose: Febuxostat, a xanthine oxidoreductase inhibitor, is a drug of choice for gout. It is available as an immediate-release formulation in the market. The objective of the present study was to produce a sustained release of Febuxostat nanosponge. Methods: Nanosponges containing Ethyl cellulose as a polymer were prepared successfully using Polyvinyl alcohol as surfactant by Emulsion Solvent Diffusion Method. The effects of different ratios of polymer and surfactant on production yield, entrapment efficiency, particle size and in vitro release were studied. Nanosponge formulations that released (≥30 %) at 1 st hour followed by controlling the release (≥75%) at six hours were further evaluated via SEM, Zeta-potentials, DSC and FTIR techniques. Results: SEM illustrates a porous and sponge-like structure. DSC and FTIR studies confirmed the formation of nanosponge and encapsulation of Febuxostat within it. The Zeta-potentials were high (-21.5 mV). The particle sizes were between 21.31 and 162.2 nm. The in vitro release study showed a sustained release pattern. Conclusions: Sustained release nanosponge formulations of Febuxostat have successfully been prepared.
... However, these systems are associated with several limitations, e.g. stability issues, toxicity due to dose dumping, gastric irritation, instability at acidic pH, high cost and less dose adjustment [2]. To overcome these problems, the focus has been drawn towards nanotechnological approaches, where the release of the drug can be controlled in a more precise manner. ...
Purpose: Febuxostat, a xanthine oxidoreductase inhibitor, is a drug of choice for gout. It is available as an immediate-release formulation in the market. The objective of the present study was to produce a sustained release of Febuxostat nanosponge. Methods: Nanosponges containing Ethyl cellulose as a polymer were prepared successfully using Polyvinyl alcohol as surfactant by Emulsion Solvent Diffusion Method. The effects of different ratios of polymer and surfactant on production yield, entrapment efficiency, particle size and in vitro release were studied. Nanosponge formulations that released (≥30 %) at 1 st hour followed by controlling the release (≥75%) at six hours were further evaluated via SEM, Zeta-potentials, DSC and FTIR techniques. Results: SEM illustrates a porous and sponge-like structure. DSC and FTIR studies confirmed the formation of nanosponge and encapsulation of Febuxostat within it. The Zeta-potentials were high (-21.5 mV). The particle sizes were between 21.31 and 162.2 nm. The in vitro release study showed a sustained release pattern. Conclusions: Sustained release nanosponge formulations of Febuxostat have successfully been prepared.
... The obvious limitations of conventional oral tablets: the fluctuation in drug plasma concentration, under/over dose of medication, frequency of dosing, poor patient adherence with resultant increased chances of missed doses, necessitate the call for modified tablet formulation. Sustained-delivery systems, a modified delivery, help maintain a near-constant plasma concentration of a drug and enhance clinical efficacy for its intended use [1]. ...
Background and Objective: Modified-release tablet of theophylline that can increase its usefulness
despite narrow therapeutic index and short half-life, is being formulated. However, the rate and
extent of release of a sustained-release delivery system can be affected by some factors. This work
is aimed at investigating the effect of agitation rates and pH of dissolution medium on release
kinetics of sustained-release theophylline tablet formulated using hydrophilic polymers.
Materials and Methods: Theophylline granules was formulated using 3 polymers (HPMC, SCMC
and Sodium alginate) to form 3 batches of granule by wet granulation method, using 95% ethanol. The granules compacted to batches of sustained-release matrix tablets. The tablet batches were
characterized for tablet properties, and dissolution studies carried out using simulated gastric and
intestinal fluid separately at different agitation rates. The data from dissolution studies were
subsequently fitted into 4 drug release kinetics models.
Results: The swelling of the 3 polymers over time was noteworthy, although there was no
significant difference between them. The release kinetic followed the Higuchi model and zero-order
releasing more than 90% over 8 hours period, with t10 and t90 released at 14 minutes and 6.8 hours
respectively. The mechanical properties of the tablets were within the acceptable limit.
Conclusion: The agitation rate and pH of the medium had no significant effect on the release of the
theophylline from the batches of matrix tablets except in the case of F1 which showed a marginally
significant effect.
... However these systems are associated with several limitations, e.g. stability issues, toxicity due to dose dumping, gastric irritation, instability at acidic pH, high cost and less dose adjustment [2]. To overcome these problems, focus has been drawn towards nano technological approaches, where release of drug can be controlled in more precise manner. ...
Purpose: To develop and evaluate nanosponge (NS) based sustained release formulations of naproxen (NAP) and ibuprofen (IBU).
Method: Six formulations of each candidate drug were prepared by emulsion solvent diffusion method, using varying ratios of polymers, i.e., ethyl cellulose and polyvinyl alcohol. The prepared formulations were evaluated for various parameters including production yield, particle size, polydispersity index, actual drug content and entrapment efficiency. Morphological, structural and thermo-analytical evaluations were performed using various techniques. In vitro release studies were performed on selected formulations.
Results: Nanosponge (NS) formulations of naproxen and ibuprofen were successfully prepared by emulsion solvent diffusion method. The particle size of naproxen and ibuprofen nanosponge formulations ranged from 347.6 to 1358 nm and 248.7 to 327.6 nm, respectively. Formulations with equal proportion of ethyl cellulose and drug resulted in nanosponges with the desired particle size. Production yield, actual drug content and entrapment efficiency was dependent on the ratio of ethyl cellulose and polyvinyl alcohol. Formulations with equal proportion showed least PDI values (0.09 for NAP and 0.07 for IBU) and highest zeta potential (-27.2 mV for NAP and -28.2 mV for IBU). Morphological, structural and thermo-analytical analysis confirmed the encapsulation of drugs in nanosponge cavities, and exhibited spherical and porous morphology. Nanosponge formulations gave a sustained release pattern, based on Higuchi model. Drug release mechanism was Fickian followed Korsmeyer-Peppas model, due probably to the porosity of the nanosponge.
Conclusion: Sustained release nanosponge formulations of naproxen and ibuprofen have successfully been prepared
... 6 Multiple terminologies are used to show a drug's effect over a longer period: sustained release, delayed release, prolonged release, modified release, extended release, controlled release, depot formulation. [7][8][9][10] Depot delivery systems consist of an aqueous or oleaginous suspension administered parenterally through the subcutaneous (SC) or muscular route, leading to formation of a depot at the site of injection which act as a reservoir from which a drug releases constantly at a predetermined level. 11 Long-acting depot formulations maintain drug plasma concentration ranging from days to months. ...
The parenteral route of administration is preferred over the oral route for treatment of many chronic and life-threatening diseases due to better patient compliance. Long-acting injectables/depot delivery systems are formulations intended for prolonged/sustained drug release over a long period of time ranging from a few days to months. Depot delivery systems enhance product quality by decreasing dosing frequency, simplifying the drug regimen. Parenteral depots reduce the relapse rate of disease and the maintenance phase of therapy, hence improving efficacy and treatment adherence. However, despite being extensively explored in the last seventy years, only a few depot products have been marketed or have reached commercial viability. The introduction of long-acting injectables of any drug took 9 to 10 years after approval of its oral formulation. Mainly the market has been conquered by long-acting injectables for antipsychotic, substance abuse, and hormonal therapy drugs. This article focuses on the preparation of long-acting injectables with special emphasis on challenges associated with formulation. The evolution and current global market trend of various depot formulations are also discussed. Insight is provided into the promising future of long-acting injectables of protein-based drugs as well as multidrug therapy, along with potential uses in the treatment of chronic diseases like HIV, Parkinson's, and Alzheimer's.
... Nanomedicine emerged as a new epoch with growth in the application of nanotechnology in the field of diagnosis and therapy. Nanoparticles are widely being used as pharmaceutical nanocarriers, and these include metallic, polymeric, vesicular, and lipidic nanoparticles [7,8]. Non-ionic surfactant vesicles (niosomes) are of intervening importance as a delivery system [9,10]. ...
Objective: The quantification of drug and stability of nanoparticulate delivery systems is one of the major apprehensions in biomedical applications. The present research work was attempted to quantify phytic acid by utilizing ultraviolet (UV) spectroscopy method and to evaluate the stability of nanovesicular (niosomes) system containing phytic acid.Methods: Niosomes containing phytic acid were developed by thin-film hydration method. Nanoformulation was subjected to stability testing as per the International Council for Harmonisation (ICH) guidelines. The formulation was stored at 30°C±2°C and 65%±5% RH, samples were withdrawn at 15th, 30th, 60th, 90th, 120th, and 180th day of analysis and examined for the integrity of vesicular/particle size, polydispersity index, zeta potential, and percent encapsulation efficiency.Results: Prepared nanoformulation displayed a straight line (y=mx+c) equation of y=−0.0309x+1.0413. Optimized batch of niosomes, which was prepared including dicetylphosphate showed zeta potential value of −36±0.36. Stability study showed that prepared niosomal formulation was stable up to 180 days at room temperature.Conclusion: Findings of the current research work suggested that UV spectroscopy method can be effectively used for the quantification of phytic acid and niosomal formulation of phytic acid. The formulation was found to be stable as per the ICH guidelines for stability testing.
... Central composite design (CCD) was used to describe the relationship between the independent variables and the responses as well as to determine the drug loading parameters for drug loaded micro-granules to reduce the number of trials which necessary to attain maximum numbers of information on product properties, and the screening was performed applying a 3 2 CCD. [13] Tab 3. List of 3 2 Central composite design. ...
... Central composite design (CCD) was used to describe the relationship between the independent variables and the responses as well as to determine the drug loading parameters for drug loaded micro-granules to reduce the number of trials which necessary to attain maximum numbers of information on product properties, and the screening was performed applying a 3 2 CCD. [13] Tab 3. List of 3 2 Central composite design. ...
Water, a unique resource on the planet earth, is essential for sustaining all forms of life, food production, economic development, and for general well being of the life on the planet. The importance of water could be gauged from the fact that while looking for life on other planets, presence of water on the planet is first examined as an indicator of the presence of life on the planet. Civilizations have been developed along the rivers. Yet, it would not be an exaggeration of fact that civilizations doomed not because the water was not available but because the water was mis-utilized resulting in unsustainable use of the resources. In present scenario, the issues related to water, such as water stress, water scarcity, water quality are gaining much importance. Water is particularly important as for agriculture for both watering of crops and for irrigation in dry season. Industrial demands for water are also high. Unfortunately, the availability of water is being increasingly threatened by the agriculture, urban and industrial consumption which also affect the underlying aquifers quality by leaching process. To cope with undergoing changes, water resources development and management have to be reconsidered by enlarging their scope across sectors and adopting effective tools to analyze current and projected infrastructure potential and operation strategies. This paper evaluates the potential improvement by the adoption of a more sophisticated information system for water resource management with integrated approach.
The purpose of this study is to prepare a bilayer tablet of Celecoxib using wet granulation technology and to formulate an optimized formulation. Celecoxib is a non-steroidal anti-inflammatory drug that inhibits the prostaglandin-generating enzyme cyclo-oxygenase 2 and reduces the pain and inflammation of Osteoarthritis. Fast release of the drug from the immediate-release layer can give a rapid onset of action which will help to reduce pain and inflammation within a short period while the maintenance dose of Celecoxib will maintain plasma concentration within the therapeutic range for 24 hours. Permeability enhancers such as Chitosan were used, which can increase the permeability as well as bioavailability of the drug. In this study, a bilayer tablet was prepared which contains an immediate release layer and a sustained release layer. HPMC K100 was used to maintain sustained release and Croscarmellose Sodium for immediate release. Sodium Starch Glycolate and Cross Povidone were used as super disintegrants. The bilayer tablets were tested for weight variation, hardness, friability, thickness, drug content, in-vitro dissolution profile, bulk density, tapped density, angle of repose, carr’s index, Hausner's ratio, and calibration curve. The granules showed satisfactory flow properties and compressibility. The best formulation L5 showed a High % drug release 96.04% release, high drug content, high hardness, and friability. Bilayer tablet is enhancing beneficial technology to control the shortcomings of the single-layered tablet. The aim of designing sustained or controlled delivery systems is to decrease the repetition of the dosing or to increase the effectiveness of the drug by localization at the site of action, lowering the dose required, or providing uniform drug delivery. The main objective of sustained release drug delivery is to make sure safety and to improve patient compliance.
The objective of this study was to formulate and evaluate Extended-release oxybutynin chloride tablets using a push-pull osmotic pump system. Oxybutynin HCL is a muscarinic antagonist used for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and frequency. PPOP are used to deliver drugs that are highly soluble in water. The drug is located in the upper compartment along with osmogent while the lower compartment consists of polymeric osmotic agents. The push pull technique has been formulated in the form of double-layer tablets by wet granulation. The nine formulations were prepared using oxybutynin chloride, HPMC, polyethylene oxide, Nacl, and other excipients, lubricants, and colouring agents. The tablets are coated with a semi-permeable membrane (cellulose acetate), followed by a film coating. The pre-compression parameters (Bulk density, tapped density, Carr’s index, Hausner ratio, and angle of repose) and post-compression parameters of the extended-release tablets (Hardness, friability, weight variation, thickness, and drug content) were all within limits. An FTIR study showed no interaction between API and HPMC and all excipients at the molecular level. In vitro release studies in 0.1 N HCl, and 6.0 phosphate buffer showed that the optimized F5 formulation extended the drug release by 93% after 24 h and the release profile was similar to a product from an innovator.
Sustained release drug delivery system is designed to sustain the release of the drug dosage forms at a predetermined rate. Sustained release formulation maintains uniform drug level in therapeutic window, improved efficacy of drug by localization at the site of action with better patient compliance, reducing the dose required, providing uniform drug delivery. The sustained release formulations minimize the frequency of drug administration and do not interfere with the therapeutic action of the drug. The use of sustained release matrix technology for antibiotics is effective in preventing the resistant of antibiotics in body on irrational use. Drug release through matrix SRDDS is determined by Polymer swelling, Water penetration, Drug dissolution, diffusion, Matrix erosion. The present article contains brief review on various formulation approaches for Sustained release drug delivery system, advantages, selection criteria for matrix SRDDS and use of cefixime trihydrate in formulating matrix SRDDS.
The present focus is on the development of sustained release formulations due to its inherent boons. There are several advantages of sustained release drug delivery over conventional dosage forms like improved patient compliance, reduction in fluctuation and increased safety margin of potent drug. The present study was aimed to prepare a sustained drug delivery system to design a controlled release oral dosage form of Cefpodoxime proxetil. The sustained release matrix tablets of Cefpodoxime proxetil were prepared by wet granulation and evaluated for different parameters such as weight variation, drug content, thickness, hardness, friability and In vitro release studies. The in vitro dissolution study was carried out for 12 hours using USP (Type- II) paddle apparatus in hydrochloride (0.1N) as dissolution media for first 2 hours and phosphate buffer (pH 6.8) for next 10 hours. Based on the in vitro dissolution data, formulation F8 was selected as the best formulation from Cefpodoxime proxetil formulations (F1 – F9) as the drug release was retarded up to 12 hours with 96.29 % and followed zero order release kinetics & drug release mechanism was diffusion.
PurposeTo formulate multiparticulate controlled-release alginate-gelatin (AL-GL) beads in order to modify gliclazide (GLZ) release rate.MethodsAL-GL beads were prepared using different glutaraldehyde concentrations and dried using either air or freeze-drying method. For comparison, calcium alginate beads (AL-beads) were prepared at different temperatures. Drug incorporation efficiency, beads swelling%, drug release rate, and kinetics in gradient conditions (USP Apparatus-4) were studied. Selected AL-GL beads, as a test formulation (T), were in-vivo compared with Diamicron® 80 mg conventional tablet (R).ResultsAL-beads curing temperature was inversely proportional to GLZ incorporation efficiency and directly proportional to beads swelling%. GLZ release from AL-beads was slow in 0.1 N HCl and very fast in pH 7.4. In case of AL-GL beads, GLZ incorporation efficiency and swelling% were inversely proportional to glutaraldehyde concentration. AL-GL beads showed zero-order release of GLZ for up to 11 h. Scanning electron microscope (SEM) images of the freeze-dried beads showed a highly porous surface. Differential scanning calorimetry (DSC) and Fourier transform infra-red (FT-IR) studies indicated an interaction between alginate and gelatin due to crosslinking, while FT-IR indicated the absence of chemical interaction with GLZ. The relative bioavailability (T/R) was 97.57, 138.34, and 143.53%, for Cmax, AUC0–72, and AUC0–∞, respectively. Tmax of T was significantly higher than R.ConclusionAL-GL beads could represent promising delivery systems for modulating GLZ release rate and minimizing the variation in its absorption.
Objective: The aim of this study was to optimize the formulation of alginate-gelatin (AL-GL) beads containing gliclazide (GLZ) employing design of experiments (DOE).
Significance: DOE enabled identification of the interaction between the studied factors, deep understanding of GLZ release pattern and acceleration of the optimization process.
Methods: A three-factor, three-level face centered design was employed. The effects of GLZ content (GLZ%, X1), polymer ratio (AL:GL ratio, X2), crosslinker concentration (glutaraldehyde, GA%, X3), and their interaction on incorporation efficiency (IE) and release rate were studied. The optimized formulation was prepared using numerical optimization and evaluated by DSC, FT-IR, SEM and release rate studies.
Results: Increasing GA% (X3) decreased IE (Y1) with the highest magnitude of effect among the studied factors. On the other hand, increasing alginate content in AL:GL ratio (X2) increased IE (Y1). The amount of GLZ released Q0.5h, Q2h(pH 1.2) and Q4h(pH 7.4) decreased by increasing GLZ% (X1) and AL:GL ratio (X2). Both drug content and AL:GL ratio appeared to affect water penetration into the gel matrix and drug release. Generally, there was a direct relationship between GA% (X3) and GLZ release in pH 1.2 (Q0.5h and Q2h). However, in pH 7.4 (Q4h), increasing GA% decreased GLZ release. In addition, increasing GA% caused deviation from zero-order release model. The actual responses of the optimized formulation were in close agreement with the predicted ones.
Conclusion: The selected factors and their levels studied in the optimization design were useful for tailoring the anticipated formulation characteristics and GLZ release pattern.
Natural biodegradable chitosan-sodium alginate polymer combination is a promising candidate for preparing drug-loaded implants because of the availability and inexpensiveness of the polymers over the semi synthetic biodegradable ones. The main objective of this research was to prepare and evaluate a biodegradable implantable system of the drug metoprolol tartrate because it plays an important role in the treatment of high blood pressure, strokes, heart attacks and angina. 70:30 and 80:20 chitosan - sodium alginate combination implants of metoprolol tartrate with 15 and 30 minutes exposure time to glutaraldehyde for hardening were prepared. It was observed that loading efficiency and drug release could be influenced by varying polymer ratios, exposure times to glutaraldehyde and excipients. The implant formulated with 25 mg drug load in 70:30 chitosan - sodium alginate ratio with 15 minutes exposure produced the maximum sustained release for 15 days. Therefore, this formulation was chosen for preparing implants containing different excipients and the implants were evaluated for loading efficiency and in-vitro drug release. Morphological characteristics of the implants were analyzed using SEM. The release mechanism was explored and explained with zero order, first order, higuchi and korsmeyer-peppas models. Implants with excipients were found to follow first order model in most cases. also good co-relations were obtained with higuchi model. According to these models, the drug release from the implants was diffusion controlled, where the drug leaving the matrix through pores and channels formed by entry of dissolution medium.
Purpose
In this study HPMC-eudragit based hydrodynamically balanced capsules of two model drugs; propranolol HCl and ofloxacin were prepared with the aim to have the gastric retention of the systems for longer periods of time with desired sustained/ controlled drug release.
Methods
Gastro-retentive capsules were prepared by simple physical blending of various low density polymers and filling into capsules. These capsules were subjected to in vitro buoyancy/ matrix integrity and dissolution studies. Weight variation, content uniformity test, UV spectral analysis and placebo interaction studies were also performed.
Results
Preliminary studies revealed that high soluble drug required higher polymer ratios to sustain drug release and maintain matrix integrity/ buoyancy than low soluble drug. In both the cases, with increase in HPMC and eudragit S100 levels there was an increase in matrix integrity and decrease in drug release rate, however much higher levels of eudragit S100 decreased matrix integrity and buoyancy. Lactose (release rate modifier) decreased matrix integrity, buoyancy and increased drug release. Mechanism of release in the both cases was found to be anomalous "non-fickian".
Conclusion
From this research and the literature available on the eudragit and HPMC matrix systems, it is evident that different categories of drugs (suitable for gastric retention), ranging from freely soluble to sparingly soluble can be suitably formulated as HPMCeudragit based GR HBS capsules with desired drug release characteristics, provided no chemical instability/ incompatibility occurs between the drug and the polymers.
Drug delivery is process or method of administering a drug substance to achieve a therapeutic effect in humans or animals. Since it is expensive and complicated to discover and market new drug entity, so recognition of therapeutic advantages of new drug delivery systems with control over drug release has become important, and needs greater attention to develop such delivery systems. In last few decades extensive wor k has been carried out in order to have spatial and temporal control over drug release from delivery systems in the body; enhance and maintain quality of drug delivery systems during manufacture and storage; protect drug from physiological degradation; imp rove patient compliance and therapeutic outcome. While designing such release systems, it is important to identify and understand mechanisms involved in the release process. Mathematical analysis of the dissolution data/ release rates is used to accurately predict the drug release from the drug products which can ultimately help to optimize the design of a new drug delivery systems with desired therapeutic efficacy and safety. Here, a brief review of different techniques used for obtaining controlled drug d elivery will be taken up for discussion along with mathematical models employed to study the release from such delivery systems.
The term “sustained release” is known to have existed in the medical and pharmaceutical literature for
many decades. It has been constantly used to describe a pharmaceutical dosage form formulated to retard
the release of therapeutic agent such that its appearance in the systemic circulation is delayed and/or
prolonged and its plasma profile is sustained in duration. Presently pharmaceutical industries are focusing
on development of sustained release formulations due to its inherent boons. Sustained release dosage
forms are designed to release a drug at a predetermined rate by maintaining a constant drug level for a
specific period of time with minimum side effects. The basic rationale of sustained release drug delivery
system optimizes the biopharmaceutical, pharmacokinetic and pharmacodynamics properties of a drug in
such a way that its utility is maximized, side-effects are reduced and cure of the disease is achieved.
There are several advantages of sustained release (matrix) drug delivery over conventional dosage forms
like improved patient compliance due to less frequent drug administration, reduction of fluctuation in
steady-state drug levels, maximum utilisation of the drug, increased safety margin of potent drug,
reduction in healthcare costs through improved therapy and shorter treatment period. The basic goal of
sustained release is provide promising way to decrease the side effect of drug by preventing the
fluctuation of the therapeutic concentration of the drug in the body and increase patient compliance by
reducing frequency of dose
Purpose: To develop and characterize an oral extended-release matrix tablet of metformin hydrochloride using a combination of a hydrophobic carrier and a hydrophilic polymer, and two types of formulation techniques. Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 3 2 factorial design. Two types of formulation techniques – melt granulation and direct compression – were evaluated. The influence of the carrier, polymer and preparation method on metformin release from the formulations in vitro as well as other physicochemical properties were studied. The release data were subjected to various release kinetic models and also compared with those of a commercial brand. Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization results indicate that the release rate of metformin HCl was directly proportional to the levels of stearic acid (SA) and polyethylene oxide (PEO) in the tablet formulations. Release rate was also dependent on the method of granulation used. Kinetic analysis showed that the formulation containing 30 %w/w of polymer exhibited release similar to that of the commercial brand with a similarity factor (f2) of 81.1. Melt granulation was more effective in extending drug release than direct compression. Release mechanism followed most closely the Korsemeyer-Peppas model with a correlation coefficient (r 2) and 0.991. Conclusion: The use of a hydrophobic carrier along with a hydrophilic polymer effectively controls the initial rapid release of a highly water soluble drug such as metformin HCl. Hot melt granulation method was especially more effective in achieving this than the direct compression method.
Sustained release dosage form of diclofenac sodium containing immediate and controlled release components was designed. Solid dispersion of immediate release component was prepared using polyvinyl pyrrolidone and mannitol carriers by common solvent method. Controlled release component was prepared in form of spherical beads by ionotropic gelation technique. The beads were prepared based on dispersing drug in solutions of ionic polysaccharides such as chitosan and sodium alginate. These dispersions were dropped into solutions of counter ions such as tetrasodium pyrophosphate and calcium chloride, respectively. The beads were also prepared using agar by dropping agar-drug hot solution into a mixture of chilled liquid paraffin and water. Then, diclofenac sodium controlled release drug delivery systems were prepared by combining the immediate release and controlled release components in different ratios. The formulations were found to be effective in providing controlled release of drug for a longer period of time. The beads were characterized by scanning electron microscopy and X-ray diffraction studies.
To control the drug release rate from the formulation, polymers are being used as the main tool. They are used as rate controlling agents, taste masking agents, protective and stabilizing agents in the oral drug delivery system. Their application in drug delivery system has been identified because of their unique properties. Advances in polymer science led to the development of novel drug delivery systems which can be modified by chemical or carrier based or drug entrapment or within pumps placed in the desired bodily compartments. To reduce the frequency of dosing and to increase the effectiveness of the drug by localisation at the site of action, to provide uniform drug delivery certain polymers are used. These polymers are classified as natural polymers, semi synthetic and synthetic polymers. By using these particular polymers the drug release can be sustained for a certain period of time and drug release can be maintained at a uniform rate. Today polymeric materials still provide most important avenues of research. This review focuses on the polymers which are used in sustained release formulations.
Sustained release aceclofenac matrix tablets constituting Kollidon sustained release (KSR) (polyvinyl acetate and povidone-based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Nine matrix tablet formulations were prepared by dry blending and direct compression method by varying the proportion of KSR and compression load with fixed percentage of aceclofenac. Among this, by comparing response variables of the prepared formulations with that of the marketed product, two formulations (KSR5 and KSR7) were chosen as the optimized formulations. The formulation showed close resemblance to commercial products and compliance with United States Pharmacopoeia USP specification. The exponential model was applied to characterize the drug release behavior from polymeric systems. It was found that non-Fickian release is predominant in tablets containing KSR with a trend toward zero-order kinetics. The study also involves in vivo evaluation of the optimized formulations to find out relevant pharmacokinetic parameters. Correlation of in vitro drug release with that of amount of drug absorbed in vivo has also been performed.
The strong influence exerted by the greatly varying normal gastrointestinal functions on the therapeutic value of a controlled-release single-unit dose is elucidated by a review of the literature. In this setting, the multiple-units dose comprising hundreds of mini-depots presents a highly preferable alternative which is due to a greater predictability and reproducibility of its therapeutic effect as well as a lowered risk of side effects. © 1978 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
The humble tablet dosage form still accounts for more than 80% of all dosage forms administered to man. This review will outline the various excipients that have been used as fillers in direct compression formulations, with particular emphasis on what is expected from such excipients in terms of their functionality. It is intended that this overview (which is by no means exhaustive) will serve as an ‘aide-memoire’ to the formulation scientist.
The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core containing the drug. The findings of the study indicated that all systems demonstrated sustained release. The properties of the polymer used and the structure of each formulation appear to considerably affect drug release and its release rate. The three-layer formulations exhibit lower drug release compared to the matrices. This was due to the fact that the barrier-layers hindered the penetration of liquid into the core and modified drug dissolution and release. The geometrical characteristics/structure of the tablets as well as the weight/thickness of the barriers-layers considerably influence the rate of drug release and the release mechanisms. Kinetic analysis of the data indicated that drug release from matrices was mainly attributed to Fickian diffusion while three-layer tablets exhibited either anomalous diffusion or erosion/relaxation mechanisms. The advantage of Carbopol formulations is that a range of release profiles can easily be obtained through variations in tablet structure and thus Carbopols are appropriate carriers of oral sustained drug delivery systems for soluble drugs such as the isosorbite mononitrate.
To evaluate pharmaceutical and pharmacotherapeutic differences in oral opioid modified-release products used in the management of chronic pain.
Searches of MEDLINE (1966-May 2006) and an extensive review of peer reviewed journals were conducted using the key search terms opioid, morphine, hydromorphone, and oxycodone. Supplemental information was gathered through the American Pain Society, and limited but relevant information was obtained from manufacturers' labeling.
All articles identified from the data sources were evaluated. Information deemed relevant was included for this review if it introduced new or well supported concepts or clarified clinical practice issues.
The recognition and treatment of pain has become a major focus of healthcare professionals. The Joint Commission on Accreditation of Healthcare Organizations mandates compliance with recommended standards, outcome measures, and other initiatives. A general review of pain management and pharmacokinetic parameters are included.
Oral modified-release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. The differences between available oral modified-release products are half-life, cost, and formulation (excipients and drug-release properties).