Formulation and evaluation of natural gum-based sustained release matrix tablets of flurbiprofen using response surface methodology

Background: This research work was done to design oral sustained release matrix tablets of water-insoluble drug, flurbiprofen, using natural gums as the matrix polymers and to evaluate the drug release characteristics using response surface methodology. The central composite design for two factors at five levels each was employed to systematically optimize drug release profile. Method: Matrix tablets were prepared by direct compression technique. Xanthan and acacia gums were taken as the independent variables. Fourier transform infrared spectroscopy studies were also performed to find out the stability of drug during the direct compression and to check the interactions between polymers and drug. Percent drug release in 2 hours and percent drug release in 8 hours were taken as response variables (Y1 and Y2, respectively). Results: Both the polymers were found to have significant effect on the drug release. Polynomial mathematical models, generated for the response variables using multiple linear regression analysis, were found to be statistically significant (P < 0.05). Contour plots were drawn to depict the relationship between response variables and independent variables. Conclusion: The formulated matrix tablets followed zero-order kinetics with negligible drug release in 0.1 N HCl at pH 1.2, which was the objective of this study to produce a formulation avoiding the gastric effects of flurbiprofen.     

Formulation and development of orodispersible sustained release tablet of domperidone

Abstract

Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug, but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30?seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200?μm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner’s ratio of the blend for compression showed good flowability and high percent compressibility. The optimized ODT-SR showed disintegration time of 21?seconds and matrix controlled drug release for 9?h. In-vivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16?h as compared 3.86?h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation.     

Oral liquid in situ gelling methylcellulose/alginate formulations for sustained drug delivery to dysphagic patients

Background: Elderly patients with swallowing dysfunction may benefit from the oral administration of liquid dosage forms with in situ gelling properties.

Aim: We have designed in situ gelling liquid dosage formulations composed of mixtures of methylcellulose, which has thermally reversible gelation properties and sodium alginate, the gelation of which is ion-responsive, with suitable rheological characteristics for ease of administration to dysphagic patients and suitable integrity in the stomach to achieve a sustained release of drug.

Method: The rheological and gelation characteristics of solutions containing methylcellulose (2.0%) and sodium alginate (0.25–1.0%) were assessed for their suitability for administration to dysphagic patients. The gel strength and in vitro and in vivo release characteristics of gels formed by selected formulations were compared using paracetamol as a model drug.

Results: Mixtures of 2.0% methylcellulose and 0.5% alginate containing 20% d-sorbitol were of suitable viscosity for ease of swallowing by dysphagic patients and formed gels at temperatures between ambient and body temperature allowing administration in liquid form and in situ gelation in the stomach. In vitro release of paracetamol from 2.0% methylcellulose/0.5% alginate gels was diffusion-controlled at pH 1.2 and 6.8. Measurement of plasma levels of paracetamol after oral administration to rats of a 2.0% methylcellulose/0.5% alginate formulation showed improved sustained release compared to that from 2.0% methylcellulose and 0.5% alginate solutions and from an aqueous solution of paracetamol.

Conclusions: Solutions of mixtures of methylcellulose and alginate in appropriate proportions are of suitable consistency for administration to dysphagic patients and form gels in situ with sustained release characteristics.     

Formulation and evaluation of ubidecarenone transdermal delivery systems

Purpose: This study is aimed to examine the feasibility of developing ubidecarenone (coenzyme Q₁₀, CoQ₁₀) transdermal delivery systems (TDS). Method: In vitro permeation study using solution formulation and pressure-sensitive adhesive (PSA) TDS and in vivo pharmacokinetic study were conducted. Results: When using solution formulations, isopropyl alcohol (103.39 ± 1.61), ethyl alcohol (81.55 ± 7.27), and the mixture of diethylene glycol monoethyl ether (DGME)/propylene glycol monolaurate (PGML) at the ratio of 60:40 (91.08 ± 26.07) showed high flux (μg/cm²/hour). The addition of fatty acids to DGME-PGML failed to show profound enhancing effects; only unsaturated fatty acids such as linoleic acid and oleic acid at 3% and caprylic acid at 3% and 10% slightly increased permeation flux. CoQ₁₀ from the acrylic PSA TDS showed biphasic permeation profile that was permeated very rapidly up to the first 12 hours, and after that, permeation rate became slower. Overall, 6% fatty acids showed high permeation rates and the highest maximum flux of 9.3 μg/cm²/hour was obtained with a formulation containing 6% lauric acid in DGME-PGML (60:40). The in vivo pharmacokinetic study using TDS with 6% fatty acids in DGME-PGML (60:40) showed that the absorption of CoQ₁₀ decreased in the following order: TDS containing linoleic acid > oral dosage form > TDS with oleic acid > TDS with lauric acid > TDS with caprylic acid > TDS with capric acid. TDS containing oleic acid showed preferable pharmacokinetic profile with respect to lower C_max, comparable AUC, and prolonged t_1/2 and T_max compared to oral administration of drug. Conclusions: For effective transdermal delivery system of CoQ₁₀, 6% linoleic acid or oleic acid in DGME-PGML (60:40) could be employed.     

Preparation and characterization of silk fibroin hydrogel as injectable implants for sustained release of Risperidone

The principal objective of the present study is to achieve a depot formulation of Risperidone by gelation of silk fibroin (SF). For this purpose, hydrochloric acid (HCl)/acetone-based and methanol-based hydrogels were prepared with different drug/polymer ratios (1:3, 1:6, and 1:15). For all the drug-loaded methanol-based hydrogels, gel transition of SF solutions occurred immediately and the gelation time was 1?min, while the gelation time of HCL/acetone-based hydrogels was around 360?min. According to the results obtined from Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) spectra, solvent systems and Risperidone could induce β-sheet structure, but HCL/acetone system had the lowest effect on induction of β-sheets. The crystallinity was increased by increasing the amount of Risperidone, and drug to polymer ratio of 1:3 possessed the highest crystallinity. Thermogravimetric analysis (TGA) indicated that increasing the amount of drug in formulation increased the stability of hydrogels, and methanol-based hydrogel with a ratio of 1:3 had the most stable structure. The release rate of Risperidone from methanol-based hydrogel at ratio of 1:3 was lower than that for HCl/acetone-based one, and it decreased by increasing the amount of Risperidone. The release of Risperidone from methanol hydrogel at ratios 1:3 and 1:6 continued up to 25?d which is acceptable for depot form of Risperidone and shows that the extended release of Risperidone was achieved successfully. In conclusion, SF hydrogel with the ability to respond to the environmental stimuli is an excellent candidate for injectable implants for extended release of Risperidone.     

A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.

Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol^® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.

Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f₂ > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC_0–36 and C_max ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.

Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol^® SR capsule.     

In situ gelling pectin formulations for oral sustained delivery of paracetamol

The purpose of this study was to evaluate the potential of a pectin formulation with in situ gelling properties for the oral sustained delivery of paracetamol (acetaminophen). The formulations consisted of dilute aqueous solutions (1% to 2% w/v) of low methoxy pectin containing calcium ions in complexed form, which on release in the acidic environment of the stomach caused gelation of the pectin. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6 h. A bioavailability of approximately 96% of that of a paracetamol solution could be achieved from gels containing an identical dose of drug formed in situ in the stomachs of rats, with appreciably lower peak plasma levels and a sustained release of drug over a period of at least 6 h.     

Oral sustained delivery of paracetamol from in situ gelling xyloglucan formulations

The purpose of this study was to evaluate the potential of a xyloglucan formulation with in situ gelling properties for the oral sustained delivery of paracetamol. Gelation of dilute aqueous solutions of the polysaccharide xyloglucan occurred in rabbit and rat stomachs as the orally administered chilled solutions attained body temperature. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6 hr. The bioavailabilities of paracetamol from the xyloglucan gels formed in situ in the stomachs of rabbits after oral administration of the liquid formulations were similar to that of a commercially available suspension containing an identical dose of paracetamol.     

Chitosan nanoparticles for prolonged delivery of timolol maleate

Timolol maleate-loaded chitosan (CS) nanoparticles were prepared by desolvation method. Experimental variables such as molecular weight of CS and amount of crosslinking agent were varied to study their effect on drug entrapment efficiency, size and release rates of nanoparticles. Chemical stability of timolol maleate (TM) and crosslinking of CS were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetric studies were performed on drug-loaded nanoparticles to investigate crystalline nature of the drug after entrapment. Results indicated amorphous dispersion of drug in the polymer matrix. Scanning electron microscopy revealed irregularly shaped particles. Mean particle size of nanoparticles ranged between 118 and 203 nm, while zeta potential ranged between +17 and +22 mV. Entrapment efficiency of nanoparticles ranged between 47.6 and 63.0%. In-vitro release studies were performed in phosphate buffer saline of pH 7.4. A slow release of TM up to 24 h was observed. A 3² full factorial design was employed and second-order regression models were used to study the response (% drug release at 4 h). Release data as analyzed by an empirical relationship suggested that drug release deviated from the Fickian trend.     

Preparation and evaluation of gel formulations for oral sustained delivery to dysphagic patients

Background: Oral sustained release gel formulations may provide a means of administering drugs to dysphagic and geriatric patients who have difficulties with handling and taking oral dosage forms. Aim: We have designed gel formulations for the oral administration of paracetamol with suitable rheological characteristics for ease of administration to patients with swallowing difficulties and sufficient integrity in the acidic environment of the stomach to achieve a sustained release of this drug. Method: Gels formed by gelatin, agar, gellan, pectin, and xyloglucan were assessed for suitable gel strength and in vitro and in vivo release characteristics. Results: Gellan (1.5%?w/v) and xyloglucan gels (1.5%?w/w) had acceptable gel strengths for ease of swallowing and retained their integrity in the rat stomach sufficiently well to sustain the release of paracetamol over a period of 6 hours. Comparison of 1.5%?xyloglucan gels with a commercially available preparation with identical paracetamol concentrations demonstrated improved sustained release properties of the xyloglucan gels. Conclusions: Gels formed by gellan and xyloglucan have suitable rheological and sustained release characteristics for potential use as vehicles for oral delivery of drugs to dysphagic patients.     

Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation

Vesicular systems endow large opportunities for the transdermal delivery of therapeutics. The present study was designed to investigate the potential of a novel class of vesicular system ‘proniosome’ as a carrier for transdermal delivery of bromocriptine (BCT). Proniosome formulations were prepared by the coacervation-phase separation method and the influence of factors like surfactant type and its amount, lipid concentration, cholesterol amount and drug content were studied. Span 60 was the most appropriate surfactant, and yielded vesicle size and percentage encapsulation efficiency of 1.3 µm and 98.9%, respectively. The developed system was characterised w.r.t. morphology, transition temperature, drug release, skin permeation and skin irritancy. Proniosomes exhibited a sustained release pattern of BCT in vitro. Skin permeation study revealed high penetration of proniosomes with sustained release of BCT through rat skin. The optimised proniosomal formulation showed enhanced transdermal flux of 16.15 μg/cm²/h as compared to 3.67 μg/cm²/h for drug dispersion. The developed formulations were observed as non-irritant to the rat skin and were found as quite stable at 4 and 25 °C for 90 days w.r.t. vesicle size and drug content. The dried proniosomal formulation could act as a promising alternative to niosomes and preferably for transdermal delivery of BCT.     

Preparation and in vitro/in vivo evaluation of a ketoprofen orally disintegrating/sustained release tablet

Context: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time. Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs.

Methods: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs). Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000. The optimal parameters of spray drying were 100°C for inlet air temperature and 1.5 mL/min for feed rate. Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP). The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated.

Results: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s. Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets. Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets. In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules.

Conclusion: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.     

Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept

Context: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability.

Objective: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation.

Materials and methods: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug.

Results and discussion: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed T_max, improved C_max and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption.

Conclusion: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.     

Formulation and Evaluation of Secnidazole or Doxycycline Dento-Oral Gels

Local delivery of antibiotics has been shown to be effective in reducing periodontopathic microorganisms. The purpose of this study is to formulate gels containing secnidazole or doxycycline hydrochloride that could be used in the treatment of periodontitis by direct periodontal intrapocket administration. Different mucoadhesive polymers were used as cellulose derivatives, carbopol and eudragit. The prepared gels were evaluated for their in vitro drug release, rheological behavior, and mucoadhesive force. Increasing the concentration of each polymer increased the viscosity, mucoadhesion, and the time required for 30 and 50% release of the original mass of each drug. Gels with appropriate balance of the above-examined parameters were selected for microbiological evaluation. Microbiological studies on selected gels showed faster release of the two drugs (expressed as inhibition zones) than the commercial products of chlorhexidine gel (Elugel®) and miconazole nitrate emulgel (Miconaz®).     

Injectable PLA-based in situ forming implants for controlled release of Ivermectin a BCS Class II drug: solvent selection based on physico-chemical characterization

In situ forming implants (ISI) prepared from biodegradable polymers such as poly(d,l-lactide) (PLA) and biocompatible solvents can be used to obtain sustained drug release after parenteral administration. The aim of this work was to study the effect of several biocompatible solvents with different physico-chemical properties on the release of ivermectin (IVM), an antiparasitic BCS II drug, from in situ forming PLA-based implants. The solvents evaluated were N-methyl-2-pyrrolidone (NMP), 2-pyrrolidone (2P), triacetine (TA) and benzyl benzoate (BB). Hansen’s solubility parameters of solvents were used to explain polymer/solvent interactions leading to different rheological behaviours. The stability of the polymer and drug in the solvents were also evaluated by size exclusion and high performance liquid chromatography, respectively. The two major factors determining the rate of IVM release from ISI were miscibility of the solvent with water and the viscosity of the polymer solutions. In general, the release rate increased with increasing water miscibility of the solvent and decreasing viscosity in the following order NMP>2P>TA>BB. Scanning electron microscopy revealed a relationship between the rate of IVM release and the surface porosity of the implants, release being higher as implant porosity increased. Finally, drug and polymer stability in the solvents followed the same trends, increasing when polymer-solvent affinities and water content in solvents decreased. IVM degradation was accelerated by the acid environment generated by the degradation of the polymer but the drug did not affect PLA stability.     

Study of the properties of the new biodegradable polyurethane PU (TEG-HMDI) as matrix forming excipient for controlled drug delivery

The purpose of this work is to study the ability of a new biodegradable polyurethane PU(TEG-HMDI) obtained by reaction of triethylene glycol (TEG) with 1,6-hexamethylene diisocyanate (HMDI) to act as matrix forming polymer for controlled release tablets and to estimate its percolation threshold in a matrix system. Matrix tablets weighing 250?mg were prepared by direct compression with 10–30% wt/wt of PU(TEG-HMDI) and anhydrous theophylline as model drug. Release studies were carried out using the paddle method. The results were analyzed using the kinetics models of Higuchi, Korsmeyer-Peppas, and Peppas and Sahlin. These studies confirm the existence of an excipient percolation threshold between 10 and 20 % wt/wt of PU(TEG-HMDI) for the different batches prepared. It has been observed that the new biodegradable polyurethane PU(TEG-HMDI) shows adequate compatibility as well as a high ability to control the drug release.     

Oral sustained delivery of theophylline and cimetidine from in situ gelling pectin formulations in rabbits

The aim of this study was to evaluate the potential of an in situ gelling pectin formulation as a vehicle for the oral sustained delivery of theophylline and cimetidine. In vitro studies demonstrated diffusion-controlled release of theophylline from 1, 1.5, and 2% w/v pectin gels. Release of this drug from 1.5% w/v pectin gels formed in situ in rabbit stomach was sustained over a period of 12 hours giving a theophylline bioavailability some seven fold higher than when administered from a commercial syrup. In contrast, interactions between cimetidine and pectin led to weak gelation of the pectin sols that prevented any meaningful determination of in vitro release characteristics. Similarly, in vivo release profiles from pectin formulations containing cimetidine were similar to that from a solution of this drug in buffer, indicative of weak gelation. Examination of the content of the rabbit stomach 5 hours after administration of 1.5% w/v pectin sols containing drug confirmed gel formation, but gels containing cimetidine were noticeably softer than those containing theophylline.     

Development and in vitro characterization of chitosan-coated polymeric nanoparticles for oral delivery and sustained release of the immunosuppressant drug mycophenolate mofetil

Objective: To develop an oral sustained release formulation of mycophenolate mofetil (MMF) for once-daily dosing, using chitosan-coated polylactic acid (PLA) or poly(lactic-co-glycolic) acid (PLGA) nanoparticles. The role of polymer molecular weight (MW) and drug to polymer ratio in encapsulation efficiency (EE) and release from the nanoparticles was explored in vitro.

Methods: Nanoparticles were prepared by a single emulsion solvent evaporation method where MMF was encapsulated with PLGA or PLA at various polymer MW and drug: polymer ratios. Subsequently, chitosan was added to create coated cationic particles, also at several chitosan MW grades and drug: polymer ratios. All the formulations were evaluated for mean diameter and polydispersity, EE as well as in vitro drug release. Differential scanning calorimetry (DSC), surface morphology, and in vitro mucin binding of the nanoparticles were performed for further characterization.

Results: Two lead formulations comprise MMF: high MW, PLA: medium MW chitosan 1:7:7 (w/w/w), and MMF: high MW, PLGA: high MW chitosan 1:7:7 (w/w/w), which had high EE (94.34% and 75.44%, respectively) and sustained drug release over 12?h with a minimal burst phase. DSC experiments revealed an amorphous form of MMF in the nanoparticle formulations. The surface morphology of the MMF NP showed spherical nanoparticles with minimal visible porosity. The potential for mucoadhesiveness was assessed by changes in zeta potential after incubation of the nanoparticles in mucin.

Conclusion: Two chitosan-coated nanoparticles formulations of MMF had high EE and a desirable sustained drug release profile in the effort to design a once-daily dosage form for MMF.     

Evaluation of Mucilage of Hibiscus rosasinensis Linn as Rate Controlling Matrix for Sustained Release of Diclofenac

This article reports the exploitation of novel hydrophilic excipient, that is, mucilage from Hibiscus rosasinensis Linn, for the development of sustained release tablet. Swelling ratio and flow properties analyses of dried mucilage powder were carried out. A 3² full factorial design was used. In factorial design, amounts of dried mucilage and dibasic calcium phosphate (DCP) were taken as independent factors and percentage drug release in 60 and 300 min and time for 80% drug release as dependent variables. Matrix tablet containing dried mucilage and diclofenac sodium (DS) was prepared through direct compression techniques. DS tablets were evaluated for hardness, friability, weight variation, in vitro drug release and water uptake, and mass loss study. The dried mucilage powder shows superior swelling capacity and excellent flow properties. Prepared tablets have acceptable hardness, friability, and uniformity in weight. It was found that batch HD8 fulfills all selected criteria. Drug release kinetics from these formulations corresponded best to the zero-order kinetics. Water uptake was independent whereas mass loss was dependent on agitation speed. The concept of similarity factor (f₂) was used to prove similarity of dissolution profile in distilled water and phosphate buffer and was found to be 90.68. It was concluded that mucilage can be used as release-retarding agent for 12 h when the drug–mucilage ratio was 1:1.5. So, matrix tablet containing dried mucilage is most suitable for sustained release of DS.     

Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8?±?18.69 to 797.7?±?12.45?nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC_0-48?hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.