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Development of Fast Dissolving Tablets of Glibenclamide Using Crospovidone and its Kneading Mixture
Abstract
Glibenclamide (GLB) is a second generation anti-diabetic drug used for the treatment of Type -II Diabetes. The drawback of the drug is, it is practically insoluble in water and so possesses poor solubility, GI absorption and bioavailability. Hence the objective of the work is to develop fast dissolving tablets of Glibenclamide using Crospovidone (CP) as super disintegrating agent. The kneading mixtures of glibenclamide were prepared with Crospovidone in the weight ratios of 1:0.5, 1:1 and 1:1.5. The mixture, GLB: CP (1:1.5) (KM) exhibited highest dissolution rate of 99.8% in 45 min. FTIR analysis of the selected kneading mixture indicated the absence of drugpolymer interaction. Hence the tablets were prepared by using the kneading mixture GLB: CP (1:1.5) (KM) by wet granulation method. Various formulations were tried and the FDT was selected which possessed optimum 2 characteristics of disintegration time of 20 sec, hardness of 3.5 kg/cm and friability of 0.34±0.61%.There is 99.9% of drug release in 20 min. The FDTs were stable without any significant changes in their initial properties of hardness, friability, disintegration time and % drug release upon storage for 4 weeks.
... The FDT S are prepared several methods like lyophillization, direct compression, sublimation, molding granulation methods using specific superdisintegrating agents have been utilized to produce the fast dissolving tablet [12][13][14] . · Direct Compression · Tablet Molding · Sublimation · Lyophilization or Freeze-Drying · Spray Drying · Mass Extrusion ...
In recent decades, a variety of pharmaceutical research has been conducted to develop new dosage forms. Fast dissolving tablets are one of the fruitful results of these researches. Fast dissolving tablets disintegrate and/or dissolve rapidly in the saliva without chewing and additional water. Mouth dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and travelling and may not have access to water. This review includes advantages, disadvantages, desired characteristics and various methods used for formulation of fast dissolving tablets.
... The Fast dissolving tablets of Phenobarbital of the best selected formula were placed in stability chamber at the temperature of 45 o C and 75% RH. The tablets were taken after 3 months and evaluated for hardness, disintegration time and drug content [15]. ...
Phenobarbital is an antiepileptic drug used in the treatment of epilepsy. Fast dissolving phenobarbitone tablets were prepared using direct compression to enhance patient compliance. The methodology technique depends on using three different superdisintegrants with different concentrations (5-15% w/w) ie, sodium starch glycolate, croscarmelose, crospovidone, with varying concentrations of microcrystalline cellulose (10-25% w/w) to improve flowability. Directly compressible mannitol used as a diluent to enhance mouth feel and compressibility. The prepared formulas were evaluated for hardness, friability, disintegration time, and content uniformity. Crospovidone 10% with microcrystalline cellulose (25%) gave the acceptable friability (0.53±0.25%) and least disintegration time (12.07±0.23 sec) and best flow property. Depending on the in-vitro and in-vivo disintegration time, the promising formulations were studied further for drug release pattern. Short term stability study (at 40º C/75% RH for 3 months), and light effect at room temperature study for the best formula.
... The ready to use soft jelly (2.5 gm) containing 5.0 mg of glibenclamide was used in the dissolution test. 5 ml of sample was withdrawn at the interval of every 5 min and the drug solution was replaced with the same volume of 0.1N HCl (pH 1.2) maintained at 37±2°C. 1 ml of the filtered sample was diluted up to 50 ml with methanol and absorbance was measured at 255 nm using HPLC [8,9]. Evaluation of taste masking 5 ml of pH 6.8 phosphate buffer (to simulate salivary pH and volume) was used to study the taste masking efficiency of jelly preparation. ...
Convenience of administration and patient compliance are gaining significant importance in the design of dosage forms. Glibenclamide is an orally administered antihyperglycemic agent, used in the management of non-insulindependant (type-2) diabetes mellitus. Difficulty in swallowing (dysphagia) is common among all age groups, especially in elderly and pediatrics. Persons suffering from dysphagia may get choked when they consume liquid formulations, thus to alleviate such problem liquid formulation of high viscosity were prepared. Formulation of oral soft gel (batches of Glibenclamide) were prepared by using hydrophilic polymer guar gum at concentration ranging from 0.3-0.5% w/v and pectin at two different concentrations (0.2% and 0.3% w/v). The batch with 0.5% w/v guar gum and 0.2%w/v pectin not only showed 85% drug release after 1h. The prepared batches were evaluated for appearance, viscosity, pH, drug content, syneresis and in vitro drug release. The optimized batch showed substantial stability when subjected to short term stability study (0-8°C and at room temperature). The problem of dose measurement by patients was outweighed as oral medicated gels are to be packed in unit dose container. Keywords: Diabetes mellitus, Jelly, Dysphagia, Glibenclamide
... A copy of this Informed Consent Form has been provided to participants by the researcher. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] : ...
Regardless of different advancement in drug delivery system, oral route remains the perfect route for the administration of the any therapeutic agents because of the low cost of therapy, ease of administration, self medication, and patient compliance. MDTs have received a great demand during the last decade because MDTs are dissolving rapidly in saliva without need of water, overcome the problem of Dysphasia i.e difficulty in swallowing and provides quick onset of action. Some tablets are designed to dissolve very fast within a few seconds are known as true FDTs. Fast or Mouth dissolving tablets are basically formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and travelling and may not have access to the water. In this review article, various conventional technologies like Freeze drying, Tablet Molding, Spray Drying, direct compression and patented technologies like Zydis, Orasolv, Durasolv, Flashtab, WOW Tab, Pharmaburst etc are described to formulate MDTs. Moreover, various excipients used to formulate MDTs, how to develop the taste for the drugs having bitter taste, and how to conduct characterization and evaluations of MDTs are also described.
... The Fast dissolving tablets of Phenobarbital of the best selected formula were placed in stability chamber at the temperature of 45 o C and 75% RH. The tablets were taken after 3 months and evaluated for hardness, disintegration time and drug content [15]. ...
Phenobarbital is an antiepileptic drug used in the treatment of epilepsy. Fast dissolving phenobarbitone tablets were prepared using direct compression to enhance patient compliance. The methodology technique depends on using three different superdisintegrants with different concentrations (5-15%w/w) i. e., sodium starch glycolate, croscarmelose, crospovidone, with varying concentrations of microcrystalline cellulose (10-25%w/w) to improve flowability. Directly compressible mannitol used as a diluent to enhance mouth feel and compressibility. The prepared formulas were evaluated for hardness, friability, disintegration time, and content uniformity. Crospovidone 10% with microcrystalline cellulose (25%) gave the acceptable friability (0. 53±0. 25%) and least disintegration time (12. 07±0. 23sec) and best flow property. Depending on the in-vitro and in-vivo disintegration time, the promising formulations were studied further for drug release pattern. Short term stability study (at 40° C/ 75% RH for 3 months), and light effect at room temperature study for the best formula.
... The FDT S are prepared several methods like lyophillization, direct compression, sublimation, molding granulation methods using specific superdisintegrating agents have been utilized to produce the fast dissolving tablet [12][13][14] . · Direct Compression · Tablet Molding · Sublimation · Lyophilization or Freeze-Drying · Spray Drying · Mass Extrusion ...
In recent decades, a variety of pharmaceutical research has been conducted to develop new dosage forms. Fast dissolving tablets are one of the fruitful results of these researches. Fast dissolving tablets disintegrate and/or dissolve rapidly in the saliva without chewing and additional water. Mouth dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and travelling and may not have access to water. This review includes advantages, disadvantages, desired characteristics and various methods used for formulation of fast dissolving tablets.
... Different approaches are being explored to enhance the solubility of poorly water soluble drugs. Some of these approaches are using different solid dispersion techniques [15,16,17] or increasing the available surfaces for dissolution [18,19,20]. Recently, the dependence of the dissolution degree of the crystal drug forms geometric shape is the subject of many studies [21,22,23,24]. ...
According to the regulation of the good manufacturing practice, pharmaceutical producers of solid oral forms have obligation to carry out drug dissolution test (in vitro) which can predict the absorption of the active components in the gastrointestinal tract (in vivo) which represents an
indicator for bioequivalent.
Objective: The objective of present study was to investigate the effect of particle size on the dissolution of glibenclamide from tablets. Final granulates from ten different batches were used for determination of particle size distribution.
Methods: Particle size analysis was performed by laser diffraction method. The dissolution of glibenclamide from tablets was performed using USP dissolution apparatus type II (paddle). Results: Mean values of percentage of glibenclamide dissolution from tablets ranged from 80% to 99%. Obtained results showed that dissolution of glibenclamide decreased with increasing particle size fraction d(0.1) and increased with increasing particle size fractions d(0.9) and D(4,3). Conclusion: The optimal ratio of the particle size and percentage of dissolution of glibenclamide was observed for the sample with particle size distribution of d(0.1) = 36m, d(0.5)= 172m, d(0.9) = 499m and D(4,3)= 229m. Mean value of percentage dissolution for glibenclamide from this sample is 97%.
... The polynomial term are (X ,X ) 1 2 2 2 included to investigate non-linearity. [25] ...
Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. It is better tolerated and less sedating than other benzodiazepines. Absorption of the drug can be impacted by oral fast dissolving dosage form; this may have implications for epilepsy in pediatrics and those having difficulty in swallowing tablets/capsules resulting in improved patient compliance. The purpose of the present investigation was to formulate and optimize clobazam oro-dissolving tablets by direct compression method using response surface methodology (RSM). Oro-dispersible tablets of clobazam were prepared by direct compression method using crospovidone (2-6%) as a superdisintegrant, microcrystalline cellulose (MCC) (20-40%) was used as diluents along with directly compressible mannitol to enhance mouth feel. A 3(2) full factorial design was applied to investigate the combined effect of two formulation variables: amount of crospovidone and MCC over the independent variables disintegration time, wetting time and percent drug release. Disintegration time showed by all formulations was found to be in the range of 24.3-193 s based on evaluation parameters the formulation containing 6% of crospovidone and 30% of MCC showed promising performance against all other formulations. The results demonstrated that the RSM could efficiently be applied for the formulation of clobazam oro-dispersible tablets; therefore, constitute an advance in the management of epileptic attacks.
Developed in the 20th century, oral medicinal jellies are still produced commercially and are still well-liked by customers. These are chewable solid dose forms that dissolve in the mouth or throat to provide either localized or systemic effects. They are taken orally. As a pharmacological composition, oral medicated jelly has some benefits but also certain drawbacks. They can be applied to the buccal, labial, gingival, and sublingual channels of drug administration, among other routes. These jellies, which come in flavors including chocolate, strawberry, pineapple, and mango, are over-the-counter drugs. They comprise medications for a number of ailments, including sore throat, antistatic, erectile dysfunction, arthritis, and hypertension. The Japanese Ministry of Health, Labour, and Welfare authorized a once-weekly oral program in 2012 The world's first medication for osteoporosis in a jelly formulation was approved by the Japanese Ministry of Health, Labour and Welfare and is to be taken orally once a week. A process of heating and congealing is used in their formulation. Oral medicated jellies serve as a new dosage form with vast uses in pharmaceuticals, nutraceuticals, and over-the-counter drugs. This study offers formulation scientists insight into new uses for this drug delivery technology by focusing on several facets of oral medicated jelly formulation. Orodispersible dose formulations provide patients additional possibilities for medication administration. They are simple to use and don't need ingesting big, solid dose forms or consuming a lot of water. This research aims to develop and assess the mouth-dissolving film of lisinopril as an ACE inhibitor for the treatment of congestive heart failure and hypertension. When compared to traditional solid oral dose forms, these forms are thought to increase the bioavailability of medications.
Background:
The injuries or wounds caused by various means will impact human lives severely. An increase in the demand for wounds or burns was observed. For better wound healing and to combat the free radical effect on the healing process, wounds must be treated with multifunctional or multipurpose dressing or gel or any other type of biomaterial.
Objectives:
The study aims to develop, optimize, and evaluate the naringin-loaded proposomal gel (PPG) for quick wound healing.
Methods:
The central composite design was employed for the optimization of proposomes. Naringin-loaded proposomes were evaluated for percentage entrapment efficiency (EE), the particle size of proposomes (PsP), and the zeta potential of proposomes (ZpP). The change in drug release profile was studied by dissolution. Furthermore, naringin and naringin-loaded proposomes, antioxidant activity was determined by 2,2- diphenyl-1-picrylhydrazyl hydrate (DPPH) reagent and ascorbic acid as a reference standard. Different gel bases were prepared, and based on various parameters, the G2 (0.6 % Carbopol 974) gel base was selected for naringin proposomes loading. The naringin-loaded PPG was evaluated for various in vitro and in vivo wound healing properties.
Results:
The optimized naringin-loaded proposomes showed extended drug release (90.78 ± 2.19%) for 72 h. The naringin-loaded PPG improved the permeability of naringin, which showed 28.91 ± 2.81% of drug release after 96 h, and the drug solution showed 9.05 ± 0.92%. IC50 values of antioxidant activity of naringin and naringin proposomes were found to be 337.31 μg/ mL and 201.86 μg/ mL, respectively. The naringin-loaded PPG showed better-wound closure on the 15th day (3.32%) compared to proposomal solution (4.75%) or naringin topical gel (4.2%).
Conclusion:
Based on the obtained results, we conclude naringin-loaded PPG can be an alternative strategic approach to deliver the naringin for quick wound healing.
Solid Dispersions were prepared by solvent evaporation technique using microcrystalline cellulose, PEG 4000, PEG 6000, PVP-K30 and Gelucire 50/13. Further objective of the project was to develop fast release surface solid dispersion of glibenclamide and compressed at low pressure to form fast-melting pharmaceutical tablet. In this study, we used sodium starch glycolate for mouth dissolving nature. The inherent hygroscopic nature of PEG could decrease the affinity for moisture of effervescent mixtures and can provide a stabilizing effect. The formulations using sodium starch glycolate and surface solid dispersion with Gelucire 50/13, PEG 4000 and 6000 were found to have better release properties. Fast Release tablet of glibenclamide might aid in dissolution due to increase in microenvironmental pH around the granules and saliva.
Ketorolac trimethamine is a class of Non steroidal anti-inflammatory drug (NSAID), commonly used to decrease the post-operative pain associated with the surgical treatment of spine deformities to treat moderate to severe pain, including pain after surgery. Ketorolac was inexpensive, safe, and well tolerated. It is a non-selective COX inhibitor the mechanism of action includes the inhibition of prostaglandin synthesis by competitively blocking the enzyme cyclo-oxygenase. Conventional ketorolac tablets which are available in market are not suitable for acute inflammatory conditions where quick onset of action is required. Besides, the conventional tablets also show poor patient compliance particularly by the geriatric and pediatric patients who experience difficulty in swallowing, and by those who are bed ridden or who are traveling and do not have an easy access of water. To provide the patients with the most conventional mode of administration, there was a need to develop rapidly disintegrating dosage form, particularly one that disintegrates and dissolves/disperses in saliva and can be administered without need of water, anytime, anywhere. Such tablets are called as fast dissolving tablets in mouth. The present investigation is aimed to formulate fast dissolving tablets of ketorolac trimethamine. The results showed low weight variation, good hardness and acceptable friability. The release profile revealed that optimized formulation (f10) showed greater release than the commercial ketorolac.
The purpose of the present work was to develop an optimized immediate release tablet for hypertensive patients using amlodipine besylate as a model drug candidate by optimization technique to produce the intended benefits. A 3 2 factorial design was employed in formulating immediate release tablet. The independent variables selected were superdisintegrants such as sodium starch glycolate and in addition to that, effect of microcrystalline cellulose was studied. The dependent variables considered for study was DT and DP 60. The tablets prepared were evaluated for thickness, uniformity of weight, hardness, friability, wetting time, in vitro disintegration time, and in vitro drug release study. The response surface plots differentiate the results between the independent and dependent variables. Apart from fulfilling all official and other specifications, the tablets exhibited higher rate of release.
The objective of our study was to formulate and evaluate proliposomes in the form of enteric-coated beads using glyburide as a model drug. The beads were enteric coated with Eudragit L-100 by a fluidized bed coating process using triethyl citrate as plasticizer. Content uniformity of glyburide was estimated using HPLC analysis of beads dissolved in methanol. These proliposomal beads formed liposomes on disintegration in phosphate buffered saline (pH 7.4), which was confirmed by transmission electron microscopy. The dissolution study of enteric-coated beads exhibited enhanced dissolution compared with pure drug and a marketed product. Liposomes can be successfully prepared for oral administration in the form of enteric-coated beads that may offer a stable system to produce liposomes for oral administration.
Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 microm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage.
The purpose of this work is to improve the dissolution and bioavailability characteristics of glibenclamide as compared to Daonil tablets (Hoechst). Solid dispersions of glibenclamide in Gelucire 44/14 (Formula 1) and in polyethylene glycol 6000 (PEG 6000) (Formula 2) were prepared by fusion method. In vitro dissolution studies showed that the dispersing systems containing glibenclamide and Gelucire 44/ 14 or PEG 6000 gave faster dissolution rates than the reference product Daonil. The in vivo bioavailability study was assessed in six healthy male volunteers in crossover design with a 1-week washout period. Both formulas were found to be significantly different from Daonil with regard to the extent of absorption as indicated by the area under serum concentration-time curve. Both formulas are not significantly different from Daonil with respect to time of peak plasma concentration Tmax. It is concluded from this pilot study that the ranking of the in vitro dissolution is similar to the ranking of in vivo availability. The ranking of the three preparations in term of dissolution rate and extent of absorption is as follows: Formula 2>Formula 1 >Daonil.