An Evaluation of the Mechanisms of Drug Release from Glyceride Bases

A series of dispersions containing theophylline in Gelucires 43/01, 54/02, 50/02, 50/13 and 55/18 was prepared and the physical structures studied using differential scanning calorimetry. The dissolution, erosion and swelling profiles of the drug dispersions were assessed. Gelucire 43/01 and 54/02 systems were found to release the drug by a simple diffusion mechanism, with no evidence for erosion or swelling being noted. Gelucire 55/18, however, showed a more complex mechanism involving both diffusion and erosion. On increasing the drug load within the matrices, the predominance of the erosion mechanism increased. Drug release from Gelucire 50/13 matrices took place principally by erosion, although the process was dominated by swelling and subsequent disintegration of the matrix, rather than simple dissolution of the base as was found for Gelucire 55/18. Gelucire 50/02 matrices also exhibited swelling, although drug release occurred predominantly via diffusion. The study, therefore, demonstrates that Gelucires may release incorporated drugs by a number of mechanisms depending on the chemical composition of the base.     

Modulating drug release profiles by lipid semi solid matrix formulations for BCS class II drug – an in vitro and an in vivo study

Abstract

The main objective of the study was to alter the dissolution profile of a practically insoluble Biopharmaceutics Classification System class II drug, aceclofenac, by formulating into lipid semisolid matrix (SSM) formulations using liquid filling technology in hard gelatin capsules, for both immediate and sustained release. SSM formulations of aceclofenac were prepared by melt fusion technique, using Gelucires (44/14, 50/13, 33/01 and 43/01), polyethylene glycols (4000 and 6000) and Poloxamer 188 at different levels. Role of additives like docusate sodium, Tween 80, Aerosil 200 and polyvinylpyrrolidone K-30 in enhancement of drug release was investigated. The optimized immediate and sustained SSM capsules were characterized in terms of assay, in vitro drug release, moisture uptake and differential scanning calorimetry. More than 80% of the drug was released within 15?min in various dissolution media studied, from Gelucire 44/14-based immediate release formulations. Incorporation of docusate sodium and Tween 80 provided further enhancement in drug dissolution when compared to plain drug and marketed tablet. SSM formulations based on Gelucire blends of 50/13 and 43/01 and 44/14 and 43/01 sustained the release of the drug for a period of 24?h following zero-order kinetics. The in vivo study of the optimized immediate release and sustained release formulations revealed significant enhancement in anti inflammatory activity (p?<?0.01) in rats. From these findings, liquid fill technique in hard gelatin capsules using Gelucire and their blends might be an efficacious approach for designing immediate or sustained drug release profiles for poorly soluble drugs like aceclofenac.     

Evaluation of release from selected thermosoftening vehicles.

Release of D&C Yellow No. 10 and anhydrous theophylline have been determined from a thermosoftening, hydrophilic matrix, Gelucire 50/13, incorporating a water-soluble additive, polyethylene glycol 4000. As additive level increased, release also increased. The effect of mixtures of Gelucire 50/13 (G50/13) and Gelucire 50/02 (G50/02) on release was also investigated as a function of temperature and pH. As the level of G50/02 increased, release decreased and became predominantly diffusional. As temperature was increased, release changed from diffusion to a mixed model of both diffusion and erosion. At basic pH, release from these composite systems became more erosional in character, possibly reflecting partial hydrolysis of the ester-linked matrices. Diffusion coefficients and apparent diffusion coefficients were calculated in G50/02 and G50/13 matrices, respectively, and were in agreement with published data.     

Effect of physical and chemical properties on drug release from selected thermosoftening vehicles.

The release profile of several drugs, (chlorpheniramine maleate, salicylic acid, hydrochlorothiazide, p-hydroxy benzoic acid, sulphafurazole, anhydrous theophylline) and the marker (D&C yellow No. 10) was detailed to determine the effect of physical and chemical properties on release from selected thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug or marker of 2.5% w/w, hydrochlorothiazide showed the slowest release from G50/02, due to its low aqueous solubility, while theophylline showed the highest release owing to its low mol. wt and moderate aqueous solubility. Release reflected two of the selection criteria, aqueous solubility and mol. wt, set forth for the drug/markers used in the study. The hydrophobic matrix, G50/02, offered no enhancement in drug release and functioned in a manner commensurate with other hydrophobic matrices. No hydrogen bonding was noted between any of the drugs or markers and the matrix. As drug or marker concentration increased from 2.5 to 15% w/w, potential hydrogen bonding was noted between p-hydroxy benzoic acid and the matrix. Theophylline no longer had the highest release being replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire excipient G50/13, chlorpheniramine maleate showed the highest release; it dissolved within the matrix at experimental temperature and lowered the matrix melting point. The matrix swelled upon exposure to the dissolution medium and it was from this swollen layer that release occurred. Sulphafurazole, hydrochlorothiazide, salicylic acid and p-hydroxy benzoic acid exerted a similar effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was observed between the drugs and matrix.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rheological behavior of drug suspensions in Gelucire mixtures and proxyphylline release from matrix hard gelatin capsules.

Mixtures of Gelucires 50/02 and 50/13 showing different hydrophilic-lipophilic balances (HLB) and of proxyphylline were used to prepare suspensions at a concentration of 25% and to manufacture extended release hard gelatin capsules by cooling. The rheological behaviors of Gelucire mixtures with and without drug were determined by adjustment of the rheograms to the Ostwald power-law and by statistical assessment of the flow index. Pure Gelucire mixtures were very slightly shear thickening whereas proxyphylline suspensions had a thixotropic shear thinning behavior. These rheological behaviors can be explained by the chemical composition and by the ratio of the two Gelucires used. Extended release of proxyphylline was obtained with all these mixtures. Drug release increased with Gelucire mixture HLB owing to higher erosion. A viscosity-release relationship was found and allowed, with these two Gelucires of extreme HLB and viscosities, to define the formulations which will give an optimal drug release, by the determination of their suspension viscosity. Modeling of dissolution kinetics has generally shown the predominance of surface erosion of the plugs relative to drug diffusion inside the matrix. This was confirmed by the better linearization of percentage released, according to Hixson-Crowell as compared with Higuchi.     

Porous cellulose matrices containing lipophilic release modifiers—a potential oral extended-release system

A multiple-unit extended-release matrix preparation was prepared by the incorporation of a hydrophilic drug (paracetamol) and lipophilic release modifiers (cetyl alcohol and paraffin) into porous cellulose matrices. The incorporation was performed using a one-step melt method. The in vitro drug release could be extended up to at least 16 h. The release rate could be controlled by varying the ratio of cetyl alcohol to paraffin. The porosity of the matrix during release increased to a larger extent than explainable by dissolution of the drug substance. This increase in porosity appears to be caused by swelling of the cellulose in combination with some erosion of the matrix material.     

Significance of lipid matrix aging on in vitro release and in vivo bioavailability

A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with paracetamol as a model drug, filled into hard gelatin capsules and stored at three different temperatures for various lengths of time. The resultant solidified matrix within the capsule was subjected to thermal analysis using differential scanning calorimetry (DSC) to ascertain its supramolecular structure. Polymorphic transformations towards more stable gelucire forms were observed upon aging the matrices, with samples stored at a temperature near the melting range of the lower temperature gelucire melting fraction showing the most profound changes. The increase in the rate of drug release from aged samples could be correlated to the alterations to the supramolecular structure of the gelucire. Accelerated drug release from aged samples could also be seen from in vivo studies using healthy human volunteers, although the extent of absorption was not affected. Therefore, even though the sustainability of release may be compromised by aging the gelucire matrices, the bioavailability of the incorporated drug is unlikely to be affected.     

Controlled drug release from Gelucire-based matrix pellets: experiment and theory

The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting drug release kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying drug release mechanisms. Drug release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas drug release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased drug release rates. Furthermore, the curing conditions significantly affected the theophylline release kinetics, whereas varying the initial drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative drug release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting drug release kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments.     

An Investigation into the Effects of Preparation Conditions and Storage on the Rate of Drug Release from Pharmaceutical Glyceride Bases

The effects of preparation conditions on the release of theophylline from Gelucires 50/13 and 55/18 have been investigated. Samples were prepared by melting physical mixes under controlled conditions, followed by either slow or fast (ambient) cooling to the solid state. A rapid cooling rate was shown to result in a slower release rate for 2% w/w dispersions in Gelucire 55/18, with the slow- and fast-cooled systems resulting in drug release via a diffusion and a mixed diffusion/erosion mechanism, respectively. At higher drug loading (30% w/w), the cooling rate did not effect the release characteristics. The erosion of Gelucire 50/13 was found to be more rapid for slowly cooled samples. Viscosity measurements were used as a means of assessing the chemical stability of the Gelucires, with evidence being found for degradation of Gelucire 55/18 on storage following heat treatment, while Gelucire 50/13 appeared to be stable. The effects of storage on the dissolution profiles of ambiently cooled systems were studied, with drug release from both bases increasing on ageing for up to 180 days.     

Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices

Weakly basic drugs and their salts exhibit a drop in aqueous solubility at high pH conditions, which can result in low and incomplete release of these drugs from sustained release formulations. The objective of this study is to modulate matrix microenvironmental pH by incorporation of acidic polymers and thus enhance the local solubility and release of basic drugs in high pH environment. Two weakly basic drugs, papaverine hydrochloride and verapamil hydrochloride with widely different pKa and aqueous solubilities at the pH of interest (6.8), were investigated for their release from hydrophilic matrices and the effect of a methacrylic (Eudragit L100-55) and an acrylic acid polymer (Carbopol 71G), were studied. For papaverine HCl, release increased with an increase in the levels of the acidic polymer used. Direct measurement of matrix pH using microelectrodes illustrated that the mechanism of release enhancement was based on modulation of microenvironmental pH. For verapamil HCl, incorporation of L100-55 resulted in release retardation due to an interaction between the anionic polymer and the cationic drug and the extent of retardation increased with an increase in the polymer level. The interaction product was characterized by NIR, FT-IR, and MTDSC techniques. Verapamil HCl release from Carbopol 71G based matrix tablets was higher than that from conventional hydroxypropyl methylcellulose (HPMC) based matrices, without any incorporated acidic additives.     

Swelling, erosion and release behavior of alginate-based matrix tablets.

Hydrophilic matrix tablets based on the alginate system have been used in relation to their possible function in modified drug delivery formulations using metronidazole as a model drug. The matrix tablets were prepared by direct compression using different grades of alginate. The effect of some factors (i.e. particle size of drug, additive used, and pH of medium) on drug release from alginate-based matrix tablets was also investigated. Swelling, erosion, and in vitro release studies of the matrix tablets were carried out in 0.1N HCl or phosphate buffer (pH 6.8). The alginate-based matrix tablets swelled or eroded while in contact with the aqueous medium and formed a continuous gel layer or underwent combination of swelling and erosion. The swelling action of alginate matrices is controlled by the rate of its hydration in the medium. Different grades of alginate insignificantly influenced the matrix swelling in acidic medium but significantly influenced in neutral medium. The presence of ammonium or calcium salts induced tablet disintegration in acidic medium. However, incorporation of calcium acetate and sodium bicarbonate can alter the tablet swelling in acidic medium. Release studies showed that all investigated factors influence the drug release. The extent of matrix swelling, erosion, and diffusion of drug determined the kinetics as well as mechanism of drug release from alginate-based matrix tablets. Most of the release data in acidic medium showed a good fit into Korsmeyer-Peppas equation but fitted well with zero-order release model, in neutral medium.     

Studies in preparation and evaluation of pH-independent sustained-release matrix tablets of verapamil HCl using directly compressible Eudragits

The objective of the present study was to investigate the impact of formulation factors on the properties of a 12h modified-release formulation of verapamil HCl. A 2(3) full factorial design was employed to investigate the influence of amount of Eudragit RS PO/RL PO (X1, a matrixing agent), HPMC K4M (X2, an auxiliary matrixing agent cum binder) and PEG 4000 (X3, channelling agent cum plasticizer). The tablets were prepared by direct compression and they were evaluated for in vitro dissolution studies in 0.1 N HCl. The time required for 90% of the drug release (t90) and similarity factor (f2) were used as responses for the selection of most appropriate batches. Swelling and fluid penetration studies were carried out in 0.1 N HCl. Time required for 90% of the drug release (t90) was calculated by using an appropriate kinetic model for each batch. An ideal drug release profile (i.e., 25% in the first hour and a constant drug release thereafter) was considered as a reference release profile for calculation of f2. Multiple regression analysis was adopted to evolve refined models for t90. The required release pattern was shown by batches containing a low level of Eudragit RS PO/RL PO (30% w/w), low level of HPMC K4M (10% w/w), and high level of PEG 4000 (15% w/w). Response surface plots are shown for t90. These formulations showed slower drug release in alkaline medium (pH 7.2). Succinic acid and KH2PO4 were incorporated in the matrix in order to obtain pH-independent drug release. Swelling of tablets and fluid penetration in the matrix were found to be influenced by the selected independent variables. This study demonstrates that the desired drug release pattern can be obtained by adopting a systematic formulation approach.     

Effect of different polymers and their combinations on the release of metoclopramide HCl from sustained-release hydrophilic matrix tablets

Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.     

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure.     

Enhanced Drug Dissolution and Bulk Properties of Solid Dispersions Granulated with a Surface Adsorbent

A combination of solid dispersion and surface adsorption techniques was used to enhance the dissolution of a poorly water-soluble drug, BAY 12-9566. In addition to dissolution enhancement, this method allows compression of the granulated dispersion into tablets. Gelucire 50/13 (polyglycolized glycerides) was used as the solid dispersion carrier. Hot-melt granulation was performed to adsorb the melt of the drug and Gelucire 50/13 onto the surface of Neusilin US2 (magnesium alumino silicate), the surface adsorbent. Dispersion granules using various ratios of drug–Gelucire 50/13–Neusilin US2 were thus prepared. The dissolution profiles of BAY 12-9566 from the dispersion granules and corresponding physical mixtures were evaluated using USP Type II apparatus at 75 rpm. The dissolution medium consisted of 0.1 N hydrochloric acid (HCl) with 1% w/v sodium lauryl sulfate (SLS). Dissolution of BAY 12-9566 from the dispersion granules was enhanced compared to the physical mixture. The dissolution of BAY 12-9566 increased as a function of increased Gelucire 50/13 and Neusilin US2 loading and decreased with increased drug loading. In contrast to the usually observed decrease in dissolution on storage, an enhancement in dissolution was observed for the dispersion granules stored at 40°C/75% relative humidity (RH) for 2 and 4 weeks. Additionally, the flow and compressibility properties of dispersion granules were improved significantly when compared to the drug alone or the corresponding physical mixture. The ternary dispersion granules were compressed easily into tablets with up to 30% w/w drug loading. The extent of dissolution of drug from these tablets was greater than that from the uncompressed dispersion granules.     

Formulation and characterization of lornoxicam-loaded cellulosic-microsponge gel for possible applications in arthritis

Rheumatoid arthritis (RA) is an autoimmune disease associated with severe joint pain. Herein, we report lornoxicam loaded cellulosic microsponge gel formulation with sustained anti-inflammatory effects that are required to manage arthritic pain. The microsponges were formulated using quasi emulsion-solvent diffusion method employing four different surfactant systems, namely polyvinyl alcohol (PVA), Tween80, Gelucire 48/16 and Gelucire 50/13. All the lornoxicam loaded microsponge formulations were extensively characterized with a variety of analytical tools. The optimized microsponge formulation was then converted into gel formulation. The lornoxicam loaded microsponge gel formulation had adequate viscosity and sufficient pharmaceutical properties as confirmed by the texture analysis and the drug release followed Super case II transport. It is noteworthy that we described the preparation of a new cellulosic polymers based microsponge system for delivery of lornoxicam to provide quick as well as lasting (sustained) anti-inflammatory effects in rats using carrageenan induced rat paw edema model. We were able to demonstrate a 72% reduction in inflammation within 4 h using the optimize transdermal gel formulation utilizing Transcutol P as permeation enhancer and with the aid of skin micro-piercing by microneedles, hence, demonstrating the potential of this microsponge gel formulation in arthritis management.     

Matrix embedded microspherules containing indomethacin as controlled drug delivery systems

This work is focused on the development of controlled drug delivery systems using different wax/fat embedded indomethacin (IM). Discrete wax/fat embedded microspherules containing indomethacin were prepared by using cetostearyl alcohol, paraffin wax and stearic acid by employing emulsification-phase separation method. These matrices have been used as barrier coatings due to their hydrophobic nature. Chemically inert and tasteless nature of wax/fats promotes their use as taste masking agents for bitter drugs. Various waxes and fats are available having different physicochemical properties to suit the needs of formulation. Methyl cellulose (MC) 1% w/v, sodium alginate (SA) 0.5% w/v and Tween-80 (TW) 1% w/v were used as emulgents. The resulting microspherules were discrete, large, spherical and also free flowing. It is revealed from the literature that natures of wax/fat emulgents were found to influence the rate of drug release. In the present work the drug content in all the batches of microspherules were found to be uniform. The rate of drug release corresponded best to first order kinetics, followed by Higuchi and zero-order equations. The release of the model drug from these wax/fat microspherules was prolonged over an extended period of time and the drug release mechanism followed anomalous (non-Fickian) diffusion controlled as well as Super Case II transport. Among the three matrix materials used, paraffin wax retarded the drug release more than the other two. Surface characteristics of microspherules have been studied by Scanning Electron Microscope (SEM). A fair degree rank of correlation was found to exist between the size and release retardation in all the three-wax/fat emulgent combinations.     

Formulation and optimization of sustained release matrix tablet of metformin HCl 500 mg using response surface methodology

The aim of the current study was to design an oral sustained release matrix tablet of metformin HCl and to optimize the drug release profile using response surface methodology. Tablets were prepared by non-aqueous wet granulation method using HPMC K 15M as matrix forming polymer. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile. HPMC K 15M (X(1)) and PVP K 30 (X(2)) were taken as the independent variables. The dependent variables selected were % of drug released in 1 hr (rel(1 hr)), % of drug released in 8 hrs (rel(8 hrs)) and time to 50% drug release (t(50%)). Contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. The formulated tablets followed Higuchi drug release kinetics and diffusion was the dominant mechanism of drug release, resulting in regulated and complete release within 8 hrs. The polymer (HPMC K 15M) and binder (PVP K 30) had significant effect on the drug release from the tablets (p<0.05). Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (p<0.05). Validation of optimization study, performed using 8 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (+/-S.D.) 0.0437+/-0.3285. Besides unraveling the effect of the 2 factors on the in vitro drug release, the study helped in finding the optimum formulation with sustained drug release.     

Enhanced drug dissolution and bulk properties of solid dispersions granulated with a surface adsorbent.

A combination of solid dispersion and surface adsorption techniques was used to enhance the dissolution of a poorly water-soluble drug, BAY 12-9566. In addition to dissolution enhancement, this method allows compression of the granulated dispersion into tablets. Gelucire 50/13 (polyglycolized glycerides) was used as the solid dispersion carrier. Hot-melt granulation was performed to adsorb the melt of the drug and Gelucire 50/13 onto the surface of Neusilin US2 (magnesium alumino silicate), the surface adsorbent. Dispersion granules using various ratios of drug-Gelucire 50/13-Neusilin US2 were thus prepared. The dissolution profiles of BAY 12-9566 from the dispersion granules and corresponding physical mixtures were evaluated using USP Type II apparatus at 75 rpm. The dissolution medium consisted of 0.1 N hydrochloric acid (HCl) with 1% w/v sodium lauryl sulfate (SLS). Dissolution of BAY 12-9566 from the dispersion granules was enhanced compared to the physical mixture. The dissolution of BAY 12-9566 increased as a function of increased Gelucire 50/13 and Neusilin US2 loading and decreased with increased drug loading. In contrast to the usually observed decrease in dissolution on storage, an enhancement in dissolution was observed for the dispersion granules stored at 40 degrees C/75% relative humidity (RH) for 2 and 4 weeks. Additionally, the flow and compressibility properties of dispersion granules were improved significantly when compared to the drug alone or the corresponding physical mixture. The ternary dispersion granules were compressed easily into tablets with up to 30% w/w drug loading. The extent of dissolution of drug from these tablets was greater than that from the uncompressed dispersion granules.     

Fast Dissolving Tablets of Fexofenadine HCl by Effervescent Method

In the present work, fast dissolving tablets of fexofenadine HCl were prepared by effervescent method with a view to enhance patient compliance. Three super-disintegrants viz., crospovidone, croscarmellose sodium and sodium starch glycolate along with sodium bicarbonate and anhydrous citric acid in different ratios were used and directly compressible mannitol (Pearlitol SD 200) to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on the in vitro dispersion time (approximately 20 s), three formulations were tested for in vitro drug release pattern in pH 6.8 phosphate buffer, short-term stability at 40°/75% RH for 3 mo and drug-excipient interaction (IR spectroscopy). Among the three promising formulations, the formulation ECP₃ containing 8% w/w of crospovidone and mixture of 24% w/w sodium bicarbonate 18% w/w of anhydrous citric acid emerged as the best (t_50% 4 min) based on the in vitro drug release characteristics compared to conventional commercial tablet formulation (t_50% 15 min). Short-term stability studies on the formulations indicated that there are no significant changes in drug content and in vitro dispersion time (P<0.05).