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Formulation and evaluation of zaltoprofen nanoemulsion gel
Abstract
Aim: The aim of the present study was to formulate and evaluate nanoemulsion gel of Zaltoprofen to sustain drug release, retard dosing frequency and minimise side effects associated with oral administration.
... A pH metre or a potentiometer was used to determine the pH of the pH Nanoemulsion formulations. The pH of the semisolid or liquid formulations was measured using electrodes that were completely dipped in them [49]. ...
The Self Nanoemulsifying Drug Delivery System (SNEDDS) is a novel drug delivery system that improves the water solubility of drugs that aren't easily dissolved in water. It is an isotropic mixture of oil, surfactant, and cosurfactant particles, as well as a co-dissolvable atom. Its drug delivery system is both thermodynamically and actively stable. Under gentle fomentation, the drug conveyance framework is trailed by weakening of watery medium, such as GI liquid, and it can come from stable O/W Nanoemulsion. Globules with a diameter of less than 100nm. It is an important type of drug delivery system for maintaining the substance's solidity as well as dissolvability. The Self Nanoemulsifying Drug Delivery System (SNEDDS) is a significant application on BCS Class II and Class IV drugs for upgrading ineffectively water soluble drugs.
... The pH of Nanoemulsion formulations was measured by a pH meter or Potentiometer. Electrodes were completely dipped into the semisolid or liquid formulations and pH was noted [39]. ...
Developments in recent drug discovery programs, yields a large proportion of novel pharmacologically active molecules that are lipophilic and poorly soluble, which is a major challenge for pharmaceutical researchers to enhance the oral bioavailability of such drug molecules. The self-nanoemulsifying drug delivery system (SNEDDS) is a promising Drug Delivery System which is well known for its prospective to improve the aqueous solubility and oral absorption of poorly water soluble drugs. SNEDDS is an isotropic mixture comprising oil, surfactant, co-surfactant and drug that form oil in water emulsion in aqueous environment under placid agitation. It can readily disperse in the aqueous environment of the gastrointestinal tract to form a fine oil-in-water emulsion with a droplet size not exceeding 100 nm under mild agitation for improving the oral bioavailability of poorly water-soluble drugs. The self nano-emulsifying Drug Delivery System (SNEDDS) is applicable on BCS Class II and Class IV Drugs for improving water Solubility of poorly water soluble drugs. It is the novel drug delivery system which is applicable for oral, parenteral, ophthalmic, intranasal and cosmetic delivery of drugs. The review presents an overview of design of formulation, preparation of components, mechanism of selfemulsification, biopharmaceutical aspects and evaluation of self nano-emulsifying drug delivery system (SNEDDS) for enhancement of oral bioavailability of poorly water soluble drugs.
... The of pH Nanoemulsion formulations was measured by a pH meter or Potentiometer. Electrodes were completely dipped into the semisolid or liquid formulations and pH was noted 49 . ...
The Self Nanoemulsifying Drug Delivery System (SNEDDS) is a Novel Drug Delivery
System for Enhancement of water solvency of ineffectively water dissolvable medications. It is isotropic combination of oil, surfactant, cosurfactant particles and it likewise containing codissolvable atom. It is Drug conveyance framework is thermodynamically and actively
steady. The medication conveyance framework under gentle fomentation is trailed by
weakening of watery media, for example, GI liquid and it can from stable O/W
Nanoemulsion. Having size of Globules is under 100nm. It is significant kind of Drug
conveyance framework to keep up the substance solidness just as dissolvability of medication item. The Self Nanoemulsifying Drug Delivery System (SNEDDS) is significant application on BCS Class II and Class IV Drugs for improving water Solubility of ineffectively water
dissolvable medications. It is critical to forestall the interfacial pressure and improving the
disintegration just as retention pace of medication atom. It is Novel Drug Delivery System is Applicable for parenteral, Ophthalmic, intranasal and restorative medication conveyance framework. What's more, the current survey depicts Preparation, parts, instrument, of self Nanoemulsification, biopharmaceutical viewpoints, portrayal strategies and uses of self Nanoemulsifying drug conveyance framework (SNEDDS) For Enhancement of oral Bioavailability of inadequately water dissolvable medications.
... Zaltoprofen (2-(10-oxo-10, 11, dihydrodibenzo [b, f] thiepin-2yl) propionic acid belongs to the class of NSAIDs, a low molecular weight drug that acts by inhibiting the bradykinin-induced responses by blocking bradykinin interaction with the bradykinin β 2 receptor on dorsal root ganglion (DRG) neurons [11]. Recent study on Zaltoprofen opened up its potential to be delivered as nanosuspension [12], Nanoemulsion gel [13] and as drug loaded biopolymeric nanoparticles [14]. All these results suggest that zaltoprofen possesses novel anti-inflammatory mechanism, which inhibits β 2 -type BK receptor function in nerve endings and shows potential to be delivered using novel drug delivery systems. ...
One-third of newly discovered drug molecules are water-insoluble, resulting in poor oral bioavailability in BCS (Biopharmaceutical Classification System). The Self Nanoemulsifying Drug Delivery System (SNEDDS) is a novel drug delivery system designed to improve the water solubility of medications that are ineffectively water soluble. It consists of an isotropic blend of oil, surfactant, and cosurfactant particles, as well as a codissolvable atom. Encapsulating a drug in SNEDDSs can lead to increased solubilization, stability in the gastro-intestinal tract, and absorption, resulting in enhanced bio-availability. The use of solid SNEDDS in the form of dry, solid powders would help to overcome the limitations of liquid SNEDDS by increasing the stability and patient compliance. Solid dosage forms are more stable and easier to handle than liquid systems, so efforts are being made to convert liquid systems to solid SNEDDS. Self-emulsification approach has been successful in oral drug delivery Spray drying, freeze drying, Micro fluidization, High Pressure Homogenizer, Sonication, and adsorption on carriers are some of the techniques that can be used to convert liquid SNEDDS into solid SNEDDS compressed into tablets. The composition of the SNEDDS can be optimized with the help of phase diagrams, whereas statistical experimental design can be used to further optimize SNEDDS. It is a novel drug delivery system that can be used for parenteral, ophthalmic, intranasal, and cosmetic drug delivery.
Plant sphingolipids (SPLs) are available as oral or topical skin care products in order to restore skin protective nature due to their chemical similarity with human skin ceramides (CERs). However, successful delivery of glucosylceramide (GlcCER) to the viable epidermis is challenging due to the skin barrier nature. The current study aimed to develop and characterize optimized nanoemulsion (NE) and nanoemulgel (NEG) formulations for topical delivery of lupin GlcCERs. The NE components were screened and pseudo-ternary phase diagrams were constructed at different hydrophilic-lipophilic balance (HLB) values of surfactant-co-surfactant mixture (Smix). Extreme vertices mixture design was developed to investigate the impact of percentage compositions of the independent variables; oil mixture (2–3%), Smix (15–18%) and aqueous component (79–83%) on the globule size of the NEs. Then, NEG was prepared from optimized 0.25% lupin GlcCER NE and Carbopol 980 gel. HLB values of 13.5 and 12 provided broader NE regions for Miglyol and isopropyl myristate, respectively. The analysis of variance of the quadratic model showed suitability of the model with R² of 99.80 and non-significant lack of fit (F value = 17.06). The optimized percentage compositions of oil phase, Smix and aqueous phase were 2.15%, 16.39% and 81.46%, respectively, with predicted globule size of 23.96 nm. Accordingly, the optimized NE globule size, poly dispersity index and zeta potential were 23.93 ± 0.25 nm, 0.069 ± 0.017 and 23.95 ± 1.20 mV, respectively. The oil globules were spherical and distributed uniformly without aggregation. The NE exhibited Newtonian flow with a viscosity of 6.75 mPa s while NEGs showed non-Newtonian flow with shear thinning property. The amount of lupin GlcCER released and penetrated into each model membrane layer at different time point was in the order of NEs > basic cream > NEGs. After 180 min, 51%, 84% and 96% of lupin GlcCER was released and penetrated into the model membrane layers from NEG, basic cream and NEs, respectively. NEGs prolonged the release and slowed down the penetration of GlcCER into the multilayer membrane model which is crucial to limit its penetration into the epidermal skin layer. Therefore, NEGs could be considered as an option for the delivery of plant GlcCER into the upper part of the skin after further ex-vivo investigation as the study is the first of its kind.
The aim of this research was to enhance the flux of transdermal drug delivery by using penetration enhancers DMSO. Skin penetration enhancers have been used to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is a viable option which penetrate into skin to reversibly decrease the barrier resistance. Penetration enhancing activity of dimethylsulphoxide (DMSO) at 5% w/w and 10% w/w concentration were determined in aqueous solution of ACV and in microemulsion formulations though calculation of transdermal flux of ACV with Keshary Chein Frenz Diffusion cell by using wistar albino rat skin. The transdermal flux of formulations PD, PD5D, PD10D, ME1 and ME10D was found to be 2.47, 50.7529, 119.7691, 238.1432 and 266.6721μg/cm2/h. The flux of microemulsion formulation ME10D was found 266.6721± 8.49 μg/cm2/h. Which showed highest value and skin flux of the drug could be enhanced up to 107 fold compared to its aqueous solution by preparing microemulsion ME10D. DMSO in microemulsion formulation is safe to the skin at 10% DMSO w/w.
Background:
Piroxicam is a non-steroidal anti-inflammatory drug belongs to BCS class II drugs having poor solubility and is associated with a number of undesirable side-effects on the stomach and kidneys in addition to gastric mucosal damage.
Aim:
The present work was to develop and characterize nanoemulgel formulation as transdermal delivery system for poorly water soluble drug, in order to overcome the troubles associated with its oral delivery and to circumvent the need of chemical penetration enhancers, which are responsible for causing skin irritation in transdermal drug delivery.
Materials and Methods:
Different nanoemulsion components (oil, surfactant and co-surfactant) were selected on the basis of solubility and emulsification ability. Pseudoternary phase diagrams were constructed using aqueous titration method to figure out the concentration range of components. Carbopol 934 was added as gel matrix to convert nanoemulsion into nanoemulgel. Drug loaded nanoemulsions and nanoemulgels were characterized for particle size, transmission electron microscopy, viscosity, conductivity, spreadability, rheological behavior, permeation studies using Wistar rat skin and stability studies. Transdermal permeation of piroxicam from nanoemulgels was determined by using Franz Diffusion cell.
Results:
The optimized nanoemulgel (BG6) contained 10% oleic acid as oil, 35% tween 80 and ethanol as surfactant co-surfactant mixture, 55% water, 0.5% drug and 0.5% w/w carbopol. The ex vivo permeation profile of optimized formulation was compared with nanoemulsion and marketed formulation (Feldene®). Nanoemulgel showed higher (P < 0.05) cumulative amount of drug permeated and flux and significantly less drug retained along with less lag time than marketed formulation.
Conclusion:
The results indicate that nanoemulgel formulation can be used as a feasible alternative to conventional formulations of piroxicam with advanced permeation characteristics for transdermal application.
The objective of this work was to increase the solubility, in vitro skin penetration and permeability of lornoxicam from semi-solid topical formulations and also to investigate the in vivo potential of nanoemulsion formulation. Optimized lornoxicam loaded nanoemulsion was prepared successfully by spontaneous self-emulsification method and the size of the stable formulations was found within the range of 102 to 200 nm. The stable nanoemulsion formulations characterized for viscosity, droplet size, transmission electron microscopy (TEM) and refractive index. In vitro permeation rate and penetration capacity of nanoemulsion and conventional gel of lornoxicam (LX) were determined. Prmeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion NE8 and the nanogel NG8 as compared to conventional gel (LG). The ability of the different drug-loaded nanocarriers (NE8 and NG8) in delivering the drug into the pig skin was investigated, using modified Franz-type diffusion cells. The drug was detected in the stratum corneum (SC) and dermis layers for the NE8 and NG8 but no trace of drug was found in case of LG in SC layer and dermis layer. In vivo studies revealed a significant increase in anti-inflammatory effects as compared with conventional gel of LX. The anti-inflammatory effects of formulation NG8 showed a significant increase in percent inhibition value when compared with control, this difference was found to be highly significant (p<0.001). This work shows for the first time that lornoxicam can be formulated into nanoemulsions and may show promise in enhancing solubility and permeation.
Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs, has strong inhibitory effects on actue and chronic inflammation. A randomized, dose-escalating study was conducted to evaluate the pharmacokinetics of single and multiple oral doses of zaltoprofen in 12 healthy Chinese volunteers. Pharmacokinetics was determined from serial blood samples obtained up to 24 h after administration of a single dose of zaltoprofen at 80, 160 or 240 mg and after multiple doses of zaltqorofen at 80 mg 3 times daily. The Cmax and AUC0-24 of zaltoprofen were found to be proportional to drug dose. Zaltoprofen was rapidly absorbed (tmax =1.46±0.83 h) and cleared (t1/2 =4.96±2.97 h). Pharmacokinetic parameters after multiple doses were similar to those after single doses. Zaltoprofen was well tolerated. These results support a tid regimen of zaltoprofen for the management of acute and chronic inflammation.
Background
Topical administration of dapsone can be an alternative route for treatment of leprosy and can also provide new therapeutic applications for an established drug. However, the physicochemical properties of dapsone make it difficult to incorporate into conventional formulations. The current study was directed toward developing a stable nanoemulsion that contains dapsone which can be adapted for topical use.
Methods
Nanoemulsions were prepared using isopropyl myristate or n-methyl-pyrrolidone as the oil phase, and characterized according to their mean droplet size, conductivity, refractive index, pH, drug content, and stability. The in vitro release of dapsone and its ability to permeate the epidermis were also evaluated.
Results
Physicochemical characterization demonstrated that nanosystems were formed, which had a uniform droplet distribution and a pH compatible with the skin surface. Use of n-methyl-pyrrolidone provided a greater nanoemulsion region and higher solubilization of dapsone, and increased the in vitro release rate when compared with a nanoemulsion prepared using isopropyl myristate. However, use of isopropyl myristate promoted an increase in in vitro epidermal permeation that followed the Higuchi model. This demonstrates the ability of a nanosystem to influence permeation of dapsone through the skin barrier. Furthermore, the nanoemulsions developed and evaluated here had ideal physicochemical stability over a 3-month period.
Conclusion
Incorporation of dapsone into a nanoemulsion may be a promising system for enabling topical delivery of dapsone, while minimizing skin permeation, for the treatment of acne. The method developed here used isopropyl myristate as the oil phase, and promoted permeation of dapsone through the skin barrier for the treatment of leprosy upon use of n-methyl-pyrrolidone as the oil phase.
Telmisartan (TEL) is an angiotensin II receptor blocker (ARB) antihypertensive agent. The aim of the present investigation was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of poorly water soluble TEL.
The solubility of TEL in various oils was determined to identify the oil phase of a SNEDDS. Various surfactants and co-surfactants were screened for their ability to emulsify the selected oil. Pseudoternary phase diagrams were constructed to identify the efficient self-emulsifying region. A SNEDDS was further evaluated for its percentage transmittance, emulsification time, drug content, phase separation, dilution, droplet size, zeta potential, pH, refractive index, and viscosity.
The developed SNEDDS formulation contained TEL (20 mg), Tween(®) 20 (43.33%w/w), Carbitol(®) (21.67%w/w), and Acrysol(®) EL 135 (32%w/w). The optimized formulation of the TEL-loaded SNEDDS exhibited a complete in vitro drug release in 15 min as compared with the plain drug, which had a limited dissolution rate. It was also compared with the pure drug suspension by oral administration in male Wister rats. The in vivo study exhibited a 7.5-fold increase in the oral bioavailability of TEL from the SNEDDS compared with the pure drug suspension.
These results suggest the potential use of the SNEDDS to improve the dissolution and oral bioavailability of poorly water soluble TEL.
Nanoemulsion has been identified as a promising delivery system for various drugs including biopharmaceuticals. Nanoemulsion is a heterogeneous system composed of one immiscible liquid dispersed as droplets within another liquid. The droplets size of nano emulsion is between 20 to 500 nm. Diameter and surface properties of droplets of nanoemulsion plays an important role in the biological behavior of the formulation. Small droplet sizes lead to transparent emulsions so that product appearance is not altered by the addition of an oil phase. In this paper various aspects of nanoemulsion have been discussed including advantages, disadvantages and methods of preparation. Furthermore new approaches of stability of formulation, effect of types and concentration of surfactant, process variables and method are also discussed to improve the stability of nanoemulsion formulation
Zaltoprofen is a non-steroidal anti-inflammatory drug (NSAID) belonging to the propionic acid class. It has strong inhibitory effects on acute and chronic inflammation. Although zaltoprofen is well tolerated orally compared to other NSAIDs, it has to be administered in three to four doses per day and was associated with ulcerogenicity, bellyache and indigestion. This makes administration of zaltoprofen unsuitable for patients with gastric ulcer and is also associated with drug interactions. Therefore, it is important to develop an alternative dosage form which is easier to administer and avoids first-pass metabolism. The transdermal route meets all the above advantages. In this study, zaltoprofen gels were prepared using carbomer with mixture solution of polyethylene glycol (PEG) 400, Tween80 and (2-hydroxypropyl)-β-cyclodextrin (HPCD) (called as T2), subsequently oleic acid as a penetration enhancer was added. Zaltoprofen gel containing T2 and oleic acid could promote the percutaneous absorption of zaltoprofen and increase AUC by 183% compared to zaltoprofen gel without T2 and oleic acid. Also, there was a finding zaltoprofen gel containing T2 and oleic acid did not cause dermal irritations in an experimental animal.
The transdermal route has been recognized as one of the highly potential routes of systemic drug delivery and provides the advantage of avoidance of the first-pass effect, ease of use and withdrawal (in case of side effects), and better patient compliance. However, the major limitation of this route is the difficulty of permeation of drug through the skin. Studies have been carried out to find safe and suitable permeation enhancers to promote the percutaneous absorption of a number of drugs. The present review includes the classification of permeation enhancers and their mechanism of action; thus, it will help in the selection of a suitable enhancer(s) for improving the transdermal permeation of poorly absorbed drugs.
Microemulsion formulations, which can be used to improve the bioavailability of poorly soluble drugs, were designed using only pharmaceutical excipients. Several types of oils and surfactants were tested and it was found that propyleneglycol monoalkyl ester and glycerol monoalkyl ester were solubilized easily in an aqueous medium by various types of surfactants. Although propyleneglycol dialkyl ester was difficult to be solubilized, the solubility was significantly enhanced by mixing it with glycerol monoalkyl ester at the ratio of 1:1. The most suitable surfactants for preparing microemulsion formulations were HCO-40, HCO-60, Tween 80, BL-9EX and Pluronic P84. The use of additional surfactants such as sodium dodecyl sulfate or sodium deoxycholate significantly improved the solubilization capacity of the oils, although formulations free of these surfactants were also available. These microemulsion formulations can be administered as a form of water-in-oil microemulsion or surfactant-oil mixture, and are expected to convert to oil-in-water microemulsion in the small intestine.