Preparation, characterization and in vivo evaluation of antihyperglycemic activity of microwave generated repaglinide solid dispersion

The influence of microwave technology on the in vitro dissolution rate and in vivo antihyperglycemic activity of a poorly water soluble drug, repaglinide (RG) was studied. Solid dispersions were prepared by conventional fusion method and microwave method using poloxamer 188. The dispersions were characterized by solubility study, dissolution study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). Microwave generated solid dispersions exhibited remarkable improvement in solubility and dissolution rate compared to that of pure RG. Results of DSC, XRD and SEM study showed conversion of crystalline form of RG to amorphous form. In vivo studies revealed that the microwave generated solid dispersion showed significant improvements in antihyperglycemic activity as compared to RG alone, thus confirming the advantage of improved pharmacological activity of RG by microwave method. In conclusion, microwave method could be considered as simple, efficient and solvent free promising alternative method to prepare solid dispersion of poorly water soluble drug RG with significant enhancement in solubility, dissolution rate and antihyperglycemic activity.     

Characterization of solid dispersions of rofecoxib using differential scanning calorimeter

Summary Solid dispersions were prepared to enhance the dissolution rate of rofecoxib. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used for the characterization of solid dispersions of polyvinyl pyrrolidone (PVP):talc:drug (3:1:1) and hydroxypropyl methylcellulose (HPMC):talc:drug (4:1:1). The DSC study indicated that PVP solid dispersion showed formation of fusion solution while HPMC solid dispersion showed no intermolecular fusion during the preparation of solid dispersions by spray dry process. The dissolution profiles and the calculated times for 75 and 90% drug release showed that dissolution rate of rofecoxib was improved in solid dispersions as compared to pure drug and physical mixtures. The DSC and XRD were successfully employed to find out the crystalline state of drug in the both solid dispersions. PVP solid dispersion gave better dissolution rate than HPMC solid dispersion. The drug was transformed from crystalline to amorphous form in PVP solid dispersion which was further conformed by XRD and DSC. The PVP:talc:drug solid dispersion can be used for the dissolution enhancement and thereby bioavailability of rofecoxib.     

Formulation of a Poorly Water-Soluble Drug Sirolimus in Solid Dispersions to Improve Dissolution

An attempt has been made to enhance solubility and dissolution of sirolimus by solid dispersion and complexation technique using various hydrophilic excipients. Sirolimus an immunosuppressant agent has low bioavailability due to its low aqueous solubility. Solid dispersion of sirolimus in PEG-6000, Poloxamer-188, and Mannitol were prepared by fusion and solvent evaporation method. Beta-CD complexation of sirolimus was prepared by kneading method. In vitro dissolution studies were carried out in 0.4% SLS in water, which showed that the solid dispersion containing PEG 6000 (1:1), which was prepared by solvent evaporation method, showed faster dissolution rate than the other formulations and β-cyclodextrin complex. Solid dispersions containing PEG 6000 was further investigated by x-ray powder diffraction, differential scanning calorimetry (DSC), and FTIR. X-ray powder diffraction and DSC patterns suggested that the drug state changed from crystalline to amorphous form in the formulation.     

Enhancement of solubility, dissolution and bioavailability of ibuprofen in solid dispersion systems

To improve its solubility, dissolution, and bioavailability; Ibuprofen-polyethylene glycol 8000 (PEG 8000) solid dispersions (SDs) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC), and evaluated for solubility, in-vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Preliminary results of this study suggested that the preparation of ibuprofen SDs using PEG 8000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and bioavailability of ibuprofen.     

Enhancement of dissolution rate of valdecoxib by solid dispersions technique with PVP K 30 & PEG 4000: preparation and in vitro evaluation

Solid dispersions of valdecoxib were prepared with the objective of dissolution enhancement by melt granulation technique using polyvinyl pyrollidone (PVP K 30) and polyethylene glycol (PEG 4000) alone (1:1) and in combination (1:0.5:0.5). Phase solubility studies showed a linear increase in valdecoxib solubility with increase in polymer concentration in both the cases. The FTIR spectroscopic studies showed the stability of valdecoxib and absence of well defined valdecoxib—PVP K 30–PEG 4000 interaction. Powder X-ray diffraction (XRD) and differential scanning calorimeter (DSC) were used to characterize the solid state of the dispersion, indicated a complete transformation of drug from crystalline to amorphous form. In vitro dissolution studies performed in 0.1 N HCl showed a significant enhance in dissolution rate when PEG 4000 and PVP K 30 were used in combination. Improved drug dissolution by both the carriers may be attributed to the improved wettability, reduction in drug crystallinity and solubilizing effects from solid dispersions of valdecoxib. Accelerated stability studies of solid dispersion with PVP K 30 and PEG 4000 does not show any significant change in the drug content and dissolution profile in 6 months study period. This study concluded that the dissolution rate of valdecoxib can be modulated by appropriate levels of hydrophilic carriers.     

Thermal analysis study of flavonoid solid dispersions having enhanced solubility

Purposes of this paper were to prepare and study new drug delivery systems for both flavanone glycosides and their aglycones based on solid-dispersion systems. These compounds are poor water soluble drugs, so an enhancement of their dissolution is a high priority. Solid-dispersion systems were prepared using PVP, PEG and mannitol as drug carrier matrices. Characterizations of these dispersions were done by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). The glass transition (T_g) temperature of PVP was only recorded in the DSC thermograms of PVP solid-dispersions of both flavanone glycosides and their aglycones, while in case of PEG and mannitol solid-dispersions endotherms of both glycosides and aglycones were noticed with low peak intensity, indicating that high percent of drug is in amorphous state. The XRD patterns of all PVP solid-dispersions of aglycones show typical amorphous materials, but XRD patterns of their glycosides reveal the presence of crystalline material. However, in all solid dispersions shifts in T_g of PVP as well as T_m of PEG were observed, indicating the existence of some interactions between drugs and matrices. SEM and TEM microscopy revealed that PVP/aglycone flavanone compounds are nanodispersed systems while all the other solid dispersions are microcrystalline dispersions. The solubility of both flavanone glycosides and their aglycones was directly affected by the new physical state of solid dispersions. Due to the amorphous drug state or nano-dispersions in PVP matrices, the solubility was enhanced and found to be 100% at pH 6.8 in the nano-dispersion containing 20 mass% of aglycones. Also solubility enhancement was occurred in solid dispersions of PEG and mannitol, but it was lower than that of PVP nano-dispersions due to the presence of the drug compounds in crystalline state in both matrices.     

Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study

The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T(g)) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the T(g) in proportion to polymer concentration. Experimental T(g) values corresponded closely with theoretical T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not increase significantly compared to the T(g) value for the drug alone. A solid dispersion formulation incorporating two different polymers-HPMC and either PVP-VA or PVP-maintained increased T(g), physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-T(g) drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.     

Formulation of betacyclodextrin based nanosponges of itraconazole

Nanosponges are betacyclodextrins crosslinked with carbonate bonds. The polymer formed is nanoparticulate in nature. Itraconazole is a BCS Class II drug that has a dissolution rate limited poor bioavailability. Rationale of the work was to enhance the solubility of Itraconazole so that the bioavailability problems are solved. Solid dispersion technique has been used for drug incorporation. The effect of a ternary component copolyvidonum on solubility of itraconazole has been studied. Phase solubility studies has been carried out with a rationale of comparing the solubilization efficiency of nanosponges, copolyvidonum and combination. The dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and photon correlation spectroscopy (PCS). It was found that the solubility of itraconazole was enhanced more than 50-folds with a ternary solid dispersion system. Using copolyvidonum in conjunction with nanosponges helps to increase the solubilization efficiency of nanosponges as evident from the phase solubility studies.     

Dissolution Enhancement and Characterization of Nimodipine Solid Dispersions with Poloxamer 407 or PEG 6000

The solid dispersion approach is an alternative to increase drug solubility. Many carriers have been studied, but there is few information about poloxamer 407 (P407). Consequently, the objective of this study was to evaluate P407 as a carrier for nimodipine solid dispersions and to compare its solubility and dissolution rates with those from polyethylene glycol (PEG 6000). The solid dispersions were prepared by the hot melting and solvent methods and they were characterized by FTIR, DSC, solubility, and dissolution tests. The results indicated a three-fold increase in solid dispersions solubility in the presence with P407 than those prepared with PEG.     

Cyclodextrin Complexed Lipid Nanoparticles of Irbesartan for Oral Applications: Design,Development, and In Vitro Characterization

Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, −30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure.     

Physicochemical characterization of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions, and finasteride: ��-cyclodextrin inclusion complexes

Finasteride is a practically insoluble in water drug that belongs to the Class II of the BCS (poor solubility and high permeability). Solid dispersions are solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. Solid dispersions are a successful strategy to improve drug release of poorly water-soluble drugs such as finasteride. Natural cyclodextrins are doughnut-shaped molecules with an internal hydrophobic cavity and a hydrophilic external surface. The lipophilic cavity enables cyclodextrins to form non-covalent inclusion complexes with a wide variety of poorly water-soluble drugs such as finasteride. The aim of this study was to investigate the formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:??-cyclodextrin inclusion complexes by solvent evaporation method using a mixture of water:ethanol (1:1). The formation of finasteride:PEG 6000 and finasteride:Kollidon K25 solid dispersions and finasteride:??-cyclodextrin inclusion complexes was investigated and characterized by differential scanning calorimetry (DSC), infrared (IR) spectroscopy, and dissolution studies from capsules containing a quantity equivalent to 5 mg of finasteride. The DSC thermograms revealed the transformation of finasteride into the amorphous state in solid dispersions with PEG 6000 and Kollidon K25, and in inclusion complexes with ??-cyclodextrin. The IR spectra demonstrated molecular interaction in solid dispersions of finasteride with PEG 6000, and in inclusion complexes with ??-cyclodextrin. Dissolution rate of solid dispersions and inclusion complexes was significantly greater than that of corresponding physical mixtures and pure drug, indicating that the formation of solid dispersions and inclusion complexes increased the solubility of the poorly soluble drug, finasteride.     

Improved dissolution of an insoluble drug using a 4-fluid nozzle spray-drying technique

A solid dispersion of the drug can be made using a polymer carrier to improve solubility. Generally, drugs become amorphized when solid dispersion is formed using a polymer carrier. In such high energy conditions, the solubility of the drug molecule is increased. We previously prepared solid dispersion using a spray-drying technique and reported its solubility and crystallinity. In this study, hydroxypropylmethylcellulose (HPMC) was used as the carrier, and tolubutamide was the model drug, which is water-insoluble. Solubility was evaluated by preparing a solid dispersion using a newly developed 4-fluid nozzle spray dryer. Observation of particle morphology by scanning electron microscopy (SEM) revealed that the particles from the spray drying were atomized to several microns, and they had also become spherical. Assessment of the crystallinity of the spray-dried particles by powder X-ray diffraction and differential scanning calorimetry demonstrated that the tolbutamide had been amorphized, forming a solid dispersion. The apparent release rate constant K of the drug from the spray-dried particles was 4 to 6 times faster than the original drug in pH 1.2, and it was also 1.5 to 1.9 times faster than the original drug in pH 6.8. The 70% release time (T(70)) of the drug from the spray-dried particles was 20 to 30 times faster than the original drug in pH 1.2 solution as well as 2 to 3 times faster than the original drug in pH 6.8 solution. Pharmaceutical preparations prepared in this way using the 4-fluid nozzle system spray dryer formed composite particles, resulting in a remarkably improved dissolution rates of the drug.     

Quercetin-PVP K25 solid dispersions

Quercetin is a flavonoid very well studied and has already entered clinical trials emerging as prospective anticancer drug candidate. In addition, quercetin has being reported to its free-radical scavenging activity and suggests potential uses for the prevention and treatment of pathologies as atherosclerosis, chronic inflammation, and others. However, quercetin is sparingly soluble in water, which may be responsible for its limited absorption upon oral administration. The solid dispersion of quercetin with polyvinylpyrrolidone Kollidon^® 25 (PVP K25) suggests an interesting way to increase quercetin solubility, antioxidant activity, and consequently bioavailability. Then, the purpose of this study was to prepare solid dispersions of quercetin with PVP K25 and evaluate their thermal characterization, antioxidant activity and quercetin improvement solubility. For this purpose, quercetin-PVP K25 solutions were dried and quercetin-PVP K25 solids were obtained. The formation of quercetin-PVP K25 solid dispersion was evaluated by solubility studies, powder X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetry (TG), and antioxidant activity. It was observed that PVP K25 was able to provide quercetin clear aqueous solutions and that quercetin solubility was increased in a PVP K25 concentration dependent manner, improving solubility even 436-fold the pure quercetin. The results obtained with XRD, FT-IR, DSC, and TG demonstrated possible quercetin-PVP K25 solid dispersion formation. Besides, the antioxidant activity of the quercetin-PVP K25 solid dispersions dissolved in aqueous solution and pure quercetin dissolved in methanol showed IC₅₀ value of 0.61 ± 0.03 and 1.00 ± 0.02 μg/mL, respectively, demonstrating that the solid dispersions presented a significant increase in antioxidant activity (P < 0.05). Putting results together, it was possible to conclude there was the formation of quercetin-PVP K25 solid dispersion.     

Physicochemical properties of the binary system glibenclamide and polyethylene glycol 4000

Solid dispersions of the antidiabetic drug glibenclamide and polyethylene glycol 4000 (macrogol 4000) were prepared by the melting method in order to increase the solubility of this poorly water-soluble compound. The temperature/composition phase diagram of the components was analyzed by hot-stage microscopy and differential scanning calorimetry, showing a monotectic. Polarized light hot stage microscopy and X-ray-powder diffraction confirmed, that glibenclamide is mainly present in a non-crystalline state after melting and solidifying of a 10% (w/w) mixture, which results in an enhanced solubility compared to physical mixtures. The solubility and dissolution rate of the drug increases clearly with decreasing drug/polymer ratio. Moreover, it was observed for the first time that a drug could crystallize as whiskers at the surface of aged solid dispersion particles. Besides relaxation phenomena, this crystallization mechanism may be responsible for a deterioration of liberation properties and bioavailability of solid dispersion based drug products with increasing storage time. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of preparation method on complexation of Cefdinir with β-cyclodextrin

The inclusion behaviour of β-cyclodextrin (βCD) was studied toward Cefdinir (CEF) in order to enhance the solubility and dissolution rate, following cyclodextrin complexation. Drug cyclodextrin solid systems were prepared by conventional methods of kneading (KN), co-evaporation (CE), spray drying (SD) and with a novel approach of microwave irradiation (MWI). The formation of inclusion complexes with βCD in the solid state, were confirmed by Differential scanning calorimetry (DSC), Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) studies, and comparative studies on the in vitro dissolution of CEF were carried out. Characterization of binary system by DSC, FTIR and SEM indicated that SD and MWI method resulted in formation of true complexes. Binary systems showed significant increase in dissolution rate as compared to plain drug. Amongst the binary systems MWI products were prepared in least time with better yield and highest dissolution rate.     

Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K_1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.     

Nimesulide/cyclodextrin/PEG 6000 ternary complexes: physico-chemical characterization, dissolution studies and bioavailability in rats

Purpose Ternary solid dispersions were prepared in order to estimate the effect of a double hydrophilization by cyclodextrins and PEG 6000 on nimesulide apparent characteristics. Ternary solid dispersions of nimesulide, cyclodextrins and PEG 6000 were characterized using DSC, FT-IR, dissolution studies and evaluating the bioavailability in rats. Methods Ternary solid dispersions were prepared either using native powders or using a preformed inclusion complex of nimesulide and cyclodextrin. Inclusion complexes and pure drug were used as references. Circulating nimesulide was measured out in rat plasma after orally administration of our different products (ternary solid dispersions, inclusion complexes and pure drug). Results An improvement of the nimesulide dissolution rate was obtained with inclusion complexes and ternary solid dispersion. In rat plasma, inclusion complexes and ternary solid dispersion improved T _max. Conclusions A second hydrophilization of inclusion complexes by PEG 6000 does not allow to achieve better results concerning nimesulide concentration in rat plasma or in dissolution studies than with inclusion complexes alone.     

Preparation and evaluation of solid dispersion for nitrendipine-carbopol and nitrendipine-HPMCP systems using a twin screw extruder

In the present study, we prepared solid dispersions of the poorly water-soluble drug nitrendipine (NIT) using the twin screw extruder method with high-molecular-weight substances, hydroxypropylmethylcellulosephthalate (HPMCP) and Carbopol (CAR), as carriers. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) evaluation showed that solid dispersions can be formed when NIT-HPMCP and NIT-CAR mixtures are treated with the twin screw extruder method. Fourier Transformation IR Spectroscopy (FT-IR) obtained with NIT-HPMCP and NIT-CAR solid dispersions indicated the presence of hydrogen bonding between the drug and the carriers. NIT-CAR solid dispersions were found to give somewhat higher dissolution than crystalline NIT and physical mixtures, while the dissolution of NIT-HPMCP solid dispersions was markedly decreased compared with the crystalline NIT and physical mixtures. These findings indicated that CAR has a greater ability to improve the dissolution of NIT than HPMCP when a twin screw extruder was employed to prepare the solid dispersions. The twin screw extruder method can be used as a simple and effective method for the preparation of solid dispersions to improve the dissolution properties of poorly water-soluble drugs when choosing proper polymers as carriers.     

Thermal,spectroscopic, and dissolution studies of ketoconazole–Pluronic F127 system

One strategy for improving the dissolution of poorly water soluble drugs is to prepare solid dispersions such as binary mixtures with hydrophilic carriers. These mixtures are generally characterized by better solubility than those of the individual components from which they are formed. In the present study, solid dispersions of ketoconazole (KET) with Pluronic F127 (PLU) were prepared by the grinding method. Solid–liquid equilibria in the system being studied were investigated by differential scanning calorimetry. A phase diagram for the whole range of compositions was constructed. The investigation revealed that ketoconazole and Pluronic F127 form a simple eutectic system containing 4.4 % w/w of ketoconazole at the eutectic point. The results of Fourier transform infrared spectroscopy and X-ray powder diffractometry studies of obtained mixtures suggest that there is no drug-carrier interaction and both components are crystalline in the solid dispersion with the whole range of composition. The prepared mixtures show an appreciable improvement of the dissolution rate of KET in 0.5 % w/v sodium lauryl sulfate. The improvement of the dissolution rate of drug is additionally increased by effective solubilization.     

Development of extended release coevaporates and coprecipitates of promethazine HCl with acrylic polymers: formulation considerations

The present investigation studied a novel extended release system of promethazine hydrochloride (PHC) with acrylic polymers Eudragit RLPO and Eudragit RS100 in different weight ratios (1 : 1 and 1 : 5) using coevaporation and coprecipitation techniques. Solid dispersions were characterized by Fourier-transformed infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), Powder X-ray diffractometry (PXRD), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) as well as solubility and in vitro dissolution studies in 0.1 n HCl (pH 1.2), double distilled water and phosphate buffer (pH 7.4). Adsorption test from drug solution to solid polymers were also performed. Selected solid dispersion system was subjected to direct compression and compressed tablets were evaluated for in vitro dissolution studies. The progressive disappearance of drug peaks in thermotropic profiles of coevaporates were related to increasing amount of polymers while SEM studies suggested homogenous dispersion of drug in polymer. Eudragit RLPO had a greater adsorptive capacity than Eudragit RS100 and thus its coevaporates in 1 : 5 ratio exhibited higher dissolution rate with 91.90% drug release for 12 h. Among different formulations, tablets prepared by Eudragit RLPO coevaporates (1 : 5) displayed extended release of drug for 12 h with 90.87% release followed by zero order kinetics (r(2)=0.9808).