Novel pH-sensitive interpenetrated network polyspheres of polyacrylamide-g-locust bean gum and sodium alginate for intestinal targeting of ketoprofen: In vitro and in vivo evaluation.

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

Effect of polymer concentration and solution pH on viscosity affecting integrity of a polysaccharide coat of compression coated tablets.

Tablets, compression coated with certain polysaccharides and intended for colon delivery, retain the integrity of the coat for an initial period of about 6 h (lag period) beyond which (post-lag period) the coat is degraded by colonic enzymes to induce drug release. This work was undertaken to investigate the factors which influence the integrity of the coat during the lag period. Core tablets containing two model drugs were compression coated with various amounts of carboxymethyl locust bean gum (CMLBG). In-vitro release of drugs, erosion of coat, and steady shear viscosity of CMLBG solutions having different concentrations and solution pH were determined. The viscosity of CMLBG that depended primarily on CMLBG concentration and partly on solution pH was responsible for erosion and integrity of the coat in the lag period. Evaluation of polymer viscosity could describe the integrity of coat of a polysaccharide coated tablet in the lag period.

In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD50) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

Effect of carboxymethylation on rheological and drug release characteristics of locust bean gum matrix tablets.

This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets.

In Vitro and In Vivo Correlation of Colon-Targeted Compression-Coated Tablets.

This study was performed to assess and correlate in vitro drug release with in vivo absorption of prednisolone (PDL) from a colon-targeted tablet prepared by compression coating of core tablet. In vivo drug absorption study was conducted using a high performance liquid chromatographic (HPLC) method, which was developed and validated for the estimation of PDL in rabbit plasma. The calibration curve showed linearity in the concentration range of 0.05 to 50 µg/mL with the correlation coefficient (r) of 0.999. The method was specific and sensitive with the limit of detection (LOD) and lower limit of quantification (LLOQ) of 31.89 ± 1.10 ng/mL and 96.63 ± 3.32 ng/mL, respectively. The extraction recovery (ER) of PDL from three different levels of quality control (QC) samples ranged from 98.18% to 103.54%. In vitro drug release study revealed that less than 10% drug was released in 6.34 h and almost complete (98.64%) drug release was achieved in the following 6 h. In vivo drug absorption study demonstrated lower values of C max, AUCtotal, and protracted T max from compression-coated tablet. The results confirmed the maximum release of drug in the colon while minimizing release in the upper gastrointestinal tract (GIT). An excellent in vitro and in vivo correlation (IVIVC) was also achieved after considering the lag time.

Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release.

This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting.

Impact of gelation period on modified locust bean-alginate interpenetrating beads for oral glipizide delivery.

In this work, the effect of hydrogelation period in the design of glipizide-loaded biopolymer-based interpenetrating network (IPN) beads was investigated. Carboxymethyl locust bean gum and sodium alginate IPN beads were prepared by ionic crosslinking method using aqueous aluminium chloride salt solution as gelation medium. The longer exposure of the IPN beads in the gelation medium caused a considerable loss of the drug (∼ 8%), and also affected their surface morphology and drug release performance. Spherical shape of the IPN beads was observed under scanning electron microscope (SEM). The diameter of IPN beads increased with increasing gelation time. The IPNs cured for 0.5h exhibited slower drug release kinetics in HCl (pH 1.2) and phosphate buffer (pH 7.4) solution than those incubated for 1-2h. The drug release occurred at a faster rate in phosphate buffer solution and continued for a minimum period of 8h. The IPNs cured for the lowest period obeyed polymer chain-relaxation phenomenon as dominating mechanism for drug release. However, all the IPNs followed anomalous mechanism of drug transport. The drug release corroborated well with pH-dependent swelling behaviors of the IPNs. Thus, IPN beads cured for 0.5h were found most suitable for controlled delivery of BCS class II anti-diabetic drug glipizide.

Novel pH-sensitive IPNs of polyacrylamide-g-gum ghatti and sodium alginate for gastro-protective drug delivery.

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca(2+) ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen.

Effect of different cross-linking methods and processing parameters on drug release from hydrogel beads.

The purpose of this work was to evaluate different methods of cross-linking for developing diltiazem-resin complex loaded carboxymethyl xanthan gum (CMXG) hydrogel beads to achieve highest possible drug entrapment and extended release for effective cardio-protection. The hydrogel beads were prepared by ionic cross-linking and dual cross-linking using simultaneous (SIM) and sequential (SEQ) methods. Among the three methods, SEQ method produced smaller sized beads having higher drug entrapment efficacy and prolonged release characteristics as evidenced from mean dissolution time and diffusion coefficient of drug. Keeping the concentration of ionic cross-linker constant, increase in the amount of covalent cross-linker and cross-linking time decreased the drug release. Higher release of the drug in acid solution was attributed to the higher solubility of the basic drug and higher swelling of the matrices in acid solution. Comparison of FTIR spectra, drug content and dissolution profiles indicated that the drug was stable in the beads when kept under stress condition up to 3 months. In conclusion, the sequential method was found superior for producing CMXG hydrogel beads as a prolonged release delivery device in cardiovascular diseases.

Development and effect of different bioactive silicate glass scaffolds: in vitro evaluation for use as a bone drug delivery system.

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2-Na2O-ZnO-CaO-MgO-P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63-66% porous and 5-50µm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas-Korsmeyer release pattern based on Fickian diffusion, while 0.5-1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass.

Ca-carboxymethyl xanthan gum mini-matrices: Swelling, erosion and their impact on drug release mechanism.

The effect of Ca(2+) ion concentration on swelling, erosion, and drug release mechanism of Ca(2+) ion cross-linked carboxymethyl xanthan gum (Ca-CMXG) matrices was investigated. By adding CaCl2 solution, carboxymethyl xanthan gum (CMXG) was converted into Ca-CMXG matrix, which was evaluated for swelling, erosion and drug release in different dissolution media. The amount of Ca(2+) ion alters the viscosity of gel layer formed around the matrices resulting in decreased water penetration into swollen layer. The changes in amount of Ca(2+) ion considerably influenced the swelling and erosion of the matrix leading to different drug release profiles. The simultaneous swelling and erosion of matrices that were controlled by the degree of cross-linking prejudiced the drug release mechanism. The release data fitted well into the Korsmeyer-Peppas equation and the combined effect of diffusion and erosion described the overall drug transport mechanism.

Effect of ionic crosslink on the release of metronidazole from partially carboxymethylated guar gum tablet.

Partially carboxymethylated guar gum (PCMGG) was crosslinked in situ by Ca(2+) ions during wet massing step of tablet preparation. The resulting tablets were evaluated for the effect of the extent of crosslinking on drug release and matrix swelling. Increase in the concentration of Ca(2+) ions increased the viscosity of gel layer and reduced the water penetration velocity into the matrix with subsequent decrease in swelling of the tablets and drug release. Beyond a certain concentration of Ca(2+) ions, the viscosity of the gel layer decreased and the drug release rate increased primarily due to erosion of the matrix. The mechanism of drug release appeared to be non-Fickian or anomalous transport. The release data also best fitted in zero order equation. The model drug, metronidazole, was compatible with the matrix materials as evident from instrumental analyses. Such formulation may provide flexibility in achieving the desired drug release rate from crosslinked matrix tablets.

Development and evaluation of Ca(+ 2) ion cross-linked carboxymethyl xanthan gum tablet prepared by wet granulation technique.

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca(+2) ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca(+2) ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca(+2) ion can modulate the drug release from CMXG matrix tablets as needed.

Nanoreticulations of etherified locust bean polysaccharide for controlled oral delivery of lamivudine.

Herein, an aqueous solution of etherified locust bean polysaccharide (ELBP) containing lamivudine was reticulated in presence of trivalent aluminium (Al(3+)) ions to nanoscale level (43.82-197.70 nm) by surfactant assisted homogenization-reticulation technique. The variation in aluminium chloride (AlCl3) strength (1.5-3.5% (w/v)) and drug:ELBP weight ratio (0.11-0.43) affected the properties of the nanoreticulations. Regardless of the variables, a maximum of ∼44% drug entrapment efficiency was noted. In simulated intestinal fluid (phosphate buffer solution, pH 7.4), the drug release rate was inversely proportional to the strength of AlCl3; but followed a proportional relationship with the drug:ELBP ratio. The mechanism of drug release shifted from Fickian diffusion to anomalous transport as the salt strength was increased above 2.5% (w/v). At intermediate drug:ELBP ratio, the drug release rate was regulated by polymer chain relaxation as opposed to simple diffusion mechanism. Fourier transform infrared spectroscopy did not show any evidence of chemical interaction between the drug and ELBP. Thermal analysis and X-ray diffraction studies suggested amorphous dispersion of drug in the nanoreticulations. Thus, the nanoreticulations were expected to absorb via intestine and phagocytosed by the virus-infected hepatic macrophages and hence could be useful for controlled delivery of lamivudine avoiding dose-dependent toxicity of the drug.

Novel etherified locust bean gum-alginate hydrogels for controlled release of glipizide.

On many occasions, homopolysaccharide hydrogel networks alone are not suitable for controlled drug delivery. In this study, interpenetrating networks (IPNs) of sodium alginate (ALG) and etherified locust bean gum (ELBG) were developed through ionotropic gelation with Al(3+) ions, tested for glipizide release, and were compared with homopolymer hydrogel networks. The degree of reticulation in IPNs was explained by the neutralization equivalent, tensile strength measurement, and drying kinetics of drug-free hydrogels. IPNs afforded a maximum of 94.40 ± 0.35% drug entrapment efficiency and exhibited slower drug release profiles up to 8 h. Al(3+)-ALG network almost completed the release of embedded drug in 3.5 h; however, the homopolymer Al(3+)-ELBG network discharged their content at a slow, uniform rate up to 8 h like the IPNs. All the networks appeared spherical under scanning electron microscope. In all cases, a faster drug release rate was assumed in phosphate buffer (pH 7.4) than in KCl/HCl buffer (pH 1.2) solution. The pH-responsive swelling of the beads was responsible for the variable drug release rate in different media. NonFickian diffusion mechanism was operative for the transport of drug from the IPNs. Moreover, IPNs gained appreciation for their better mechanical strength (63.79 ± 1.59 MPa) than Al(3+)-ELBG network. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and X-ray diffraction analyses indicated a compatible environment for drug encapsualtion and release from the IPNs. The drug release curves of Al(3+)-ELBG and IPNs were found similar to a reference product. Hence, Al(3+)-ELBG and IPNs could be useful in controlling diabetes over longer periods.

Novel gastroulcer protective micro(hydro)gels of sulfated locust bean gum-aluminium complex for immediate release of diclofenac sodium.

In this study, carboxymethyl sulfate derivative (CLBS) of locust bean gum (LBG) was synthesized by varying the strength of sulfating reagent. CLBS was characterized by Fourier transform infrared (FTIR) spectroscopy, elemental analysis, and viscosity measurements. Furthermore, the degree of sulfation and carboxymethylation in CLBS was determined. Novel micro(hydro)gel particles of CLBS were fabricated in basic aluminum chloride solution and different concentration of diclofenac sodium was incorporated into these particles. Differential scanning calorimetry and FTIR analyses did not suggest any drug-polymer interaction. Spherical morphological structures of the particles were evident under scanning electron microscope. Regardless of the formulation variables, a maximum of ~60% drug entrapment efficiency was achieved. For a higher degree of substitution, CLBS particles disintegrated rapidly (~20 min) and released >80% drug in acidic medium (pH1.2 and pH4.0) in 60 min. However, the particles liberated only ~60% drug in phosphate buffer medium (pH6.8) during this period. Following disintegration of the particles, the pH of gastric environment elevated. In stomach histopathology, the ulcers were scored and it was estimated that CLBS afforded ~86% protection to the gastric mucosa from ulceration. Thus, the micro(hydro)gel particles of CLBS-aluminium complex could be useful for immediate analgesic effect of the drug without any significant gastric distress.

Study of the release mechanism of Terminalia chebula extract from nanoporous silica gel.

Sol/gel-derived silica gel was prepared at room temperature from tetraethyl orthosilicate precursor. The extracts of Terminalia chebula (Haritoki) were entrapped into the porous silica gel. Fourier transform infrared analysis revealed the proper adsorption of herbal values in the nanopores of the silica gel. Porosity was estimated by transmission electron microscope studies. The release kinetics of the extract in both 0.1 N HCl, pH 1.2, and Phosphate-buffer saline (PBS), pH 7.2, were determined using UV-Vis spectroscopy. Different dissolution models were applied to release data in order to evaluate the release mechanisms and kinetics. Biphasic release patterns were found in every formulation for both the buffer systems. The kinetics followed a zero-order equation for first 4 h and a Higuchi expression in a subsequent timeline in the case of 0.1 N HCl. In the case of PBS, the formulations showed best linearity with a first-order equation followed by Higuchi's model. The sustained release of the extract predominantly followed diffusion and super case II transport mechanism. The release value was always above the minimum inhibitory concentration.

Smart reticulated hydrogel of functionally decorated gellan copolymer for prolonged delivery of salbutamol sulphate to the gastro-luminal milieu.

A partially hydrolysed poly(acrylamide)-grafted-gellan (HPAmGG) copolymer was synthesised and characterised. Temperature- and concentration-dependent rheology and gel-like property of Gelrite gellan (GG) disappeared in HPAmGG copolymer. Smart HPAmGG hydrogel was fabricated with variation in aluminium chloride (AlCl(3)) strength and initial drug loading. The hydrogel reticulates seemed spherical and showed a maximum of ∼65% drug retention, but the assay was ∼22% lower for GG hydrogel. The drug release rate was inversely proportional to AlCl(3) strength in simulated intestinal milieu (pH 7.4), but approximated a proportional relationship with drug load. HPAmGG hydrogel liberated only 10-17% content in simulated gastric milieu (pH 1.2) in 2 h. The release data correlated well with the pH-dependent swelling of hydrogel and indicated the anomalous drug diffusion mechanism. Differential scanning calorimetry, X-ray diffraction, and high-performance liquid chromatography analyses confirmed the amorphous nature of the drug and its stability in fresh and aged hydrogel. Hence, smart HPAmGG hydrogel had the potential to prolong drug release mimicking the variable pH of the gastrointestinal tract.

Development and evaluation of xanthan gum-facilitated ethyl cellulose microsponges for controlled percutaneous delivery of diclofenac sodium.

In this study, xanthan gum-facilitated ethyl cellulose microsponges were prepared by the double emulsification technique and subsequently dispersed in a carbopol gel base for controlled delivery of diclofenac sodium to the skin. Scanning electron microscopy revealed the porous, spherical nature of the microsponges. Increase in the drug/polymer ratio (0.4:1, 0.6:1, 0.8:1, m/m) increased their yield (79.1-88.5%), drug entrapment efficiency (50.0-64.1%), and mean particle diameter (181-255 µm). Compared to the microsponges with high drug/polymer ratio (0.8:1, m/m), the flux of entrapped drug through excised rat skin decreased by 19.9% and 17.0%, respectively, for the microsponges prepared at low and intermediate drug/polymer ratios. When an equivalent amount of pure drug (not entrapped into microsponges) was dispersed into the gel base and the flux was compared, the microsponges (drug/polymer ratio 0.8:1, m/m) were found to reduce the flux by 33.3%. Whether the drug was dispersed either in un-entrapped or entrapped form into the gel base, the drug permeation through rat skin followed Higuchi's diffusion kinetic model. The microsponges prepared at the lowest drug/polymer ratio exhibited a comparatively slower drug permeation profile and were hence considered most suitable for controlled drug delivery application. FTIR spectroscopy and DSC analyses indicated the chemically stable, amorphous nature of the drug in these microsponges. The gel containing these optimized microsponges was comparable to that of a commercial gel formulation and did not show serious dermal reactions. Hence, the microsponge system obtained at the lowest drug/polymer ratio could be useful for controlled release of diclofenac sodium to the skin.

Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: in vitro and in vivo evaluation.

In this study, nanovesicles were developed for brimonidine tartrate by film hydration technique and dispersed in viscous carbopol solution for ocular delivery. Scanning electron microscopy revealed spherical shape of the vesicles. As high as 32.27% drug entrapment efficiency was achieved depending upon the surfactant/cholesterol molar ratio (7:4 to 7:8). The vesicles were in the size range of 298.0-587.9 nm. Release study showed a biphasic drug-release pattern for the lyophilized vesicular formulation in buffered saline solution, i.e., initial burst release followed by gradual release over the period of 8 h. On contrary, the isolated vesicles reduced the burst effect in 3 h by two to three times and the drug release was comparatively slower at the intermediate ratio in both cases. With variation in cholesterol content, the drug release followed either first order or Higuchi's kinetics. Physically the lyophilized vesicular formulations were more stable at refrigerated temperature. DSC and X-RD analyses indicated loss of drug crystallinity in the vesicles. FTIR spectroscopy did not reveal any interaction between drug and excipients. The lyophilized formulation showed better ocular hypotensive activity than marketed drops on albino rabbits and in vivo efficacy was sustained up to 7.5 h. Furthermore, the formulation was found to be non-irritant to the rabbit eye. Hence, the lyophilized vesicles, when dispersed in viscous carbopol solution, had the potential in reducing dosing frequency and could improve patient compliance.