Viscosity Grades Of Hydroxypropyl Methylcellulose Research Articles

Pharmacological Efficacy of Insulin-Loaded Granules Made Up of Various Grades of Hydroxypropyl Methylcellulose in Normal Rats

The aim was to study the potential of various hydroxypropyl methylcellulose (HPMC) grades (K100LV, E50LV, E5LV, E4M, K4M and K100M) in enhancing oral bioavailability of insulin. Enteric coated insulin-loaded-HPMC granules were compared with peroral solution of zinc insulin in glycerine IP (0.788 mg/0.2 ml). Since lowering of blood glucose levels (BGLs) was used as pharmacological response, the area above curve 24 0 AAC was measured as a pharmacokinetic parameter instead of area under curve (AUC) for calculating bioavailability or pharmacological efficacy. In vitro studies showed that insulin release from granules was barred in acidic medium while almost complete release took place in basic medium upto 8h. In vivo studies in normal rats showed a maximum blood glucose reduction by K100LV based insulin-loaded granules, which corresponded to a relative pharmacological efficacy of ~1.4% and absolute pharmacological efficacy of ~0.5%. In contrast, neither control granules nor control (peroral) solution showed a comparable effect. The multiple comparison post-hoc test, least square difference (LSD; at p = 0.05), showed a significant difference of K100LV-, E50LV-, E5LV-, E4M- based insulin-loaded granules from placebo and of K100LV-, E50LV- based insulin-loaded granules from peroral solution. The potential of insulin-loaded HPMC granules followed a general order of K100LV > E50LV > E5LV > E4M > K4M > K100M in lowering of % BGLs. Therefore, low viscosity grades of HPMC are efficient in enhancing oral insulin absorption as compared to high viscosity grades.

Effect of Various Types of Hydroxypropyl Methylcellulose (HPMC) Films on Surface Free Energy and Contact Angle

The aim of this study was to investigate the physicochemical characteristics of various viscosity grades of hydroxypropyl methylcellulose (HPMC) for mucoadhesive buccal films. The HPMC used in this study was K4M, K15M and K100M which their viscosity were 4000, 15000 and 100000 mPas respectively. Using HPMC as film forming base matrix, all intrinsic characteristics of each HPMC grade is required as basic knowledge for the development of mucoadhesive buccal films. To understand the primary essential parameters, surface free energy and contact angle of various HPMC grades were determined. Sessile drop technique was used in this study to determine contact angle of HPMC and surface free energy was then evaluated by using the Wu’s equation. The results showed that the increase in viscosity of HPMC film tended to decrease the polar force and total surface free energy but increased the contact angle. These parameters indicated that the hydrophilic character of HPMC was influenced by its viscosity. Our study suggested that the polar and dispersive force detected by sessile drop technique could be beneficial for the further design and development of mucoadhesive buccal films.

Optimization of Polymer Concentration for Designing of Oral Matrix Controlled Release Dosage Form

Patient’s compliance can be enhanced by using extended release drug delivery systems which allow decreasing the number of daily doses, and helping to maintain uniform drug levels and increase the safety margin for high-potency drugs. Hydroxypropyl methylcellulose (HPMC) is the most commonly used hydrophilic polymer for the preparation of oral controlled drug delivery systems. This research was conducted with the aim of developing matrix based oral controlled release tablets for the drug diclofenac sodium using different viscosity grades of HPMC (K15M) and to compare the drug release characteristics with those of a commercial product, Voltaren® SR 100. Similarity factor (f2), values in between test formulation and marketed preparation was calculated to choose the best formulation. The release kinetics from various matrices was also studied. Increasing in polymer content reduced the rate of drug release. At the same polymer content in the matrix, the drug release was most sustained with tablets prepared using HPMC (K15M). Out of all the formulations studies, matrix tablets containing 40% of HPMC (K15M) showed comparable dissolution profile to that of the marketed preparation as indicated by a similarity factor value of (f2) 88.30%. The release of drug from marketed preparation and matrix with HPMC (K15M) 40% was found to be a diffusion drug mechanism as per Higuchi equation.

Solubility and dissolution enhancement of HPMC ‑ based solid dispersions of carbamazepine by hot‑melt extrusion technique

The objective of this study was to investigate solid dispersions (SDs) of poorly water soluble drug carbamazepine (CBZ), prepared using low viscosity grade hydroxypropyl methyl cellulose (HPMC) (Methocel® E3 LV and Methocel® E5 LV) by hot‑melt extrusion (HME) technology. Saturation solubility and dissolution profile of CBZ was studied. Characterization of hot‑melt extruded samples was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X‑ray diffraction studies (XRD). The result of the study showed the conversion of crystalline form of drug into amorphous form indicating increase in saturation solubility and dissolution rate of CBZ. Key words: Carbamazepine, hot‑melt extrusion, hydroxypropyl methyl cellulose

Efficacy of gastro-retentive forms of ecabet sodium in the treatment of gastric ulcer in rats

The purpose of the present study is to investigate the influence of gastric retention of ecabet sodium (ECS) on its mucoprotective effect in rat ulcer models. Mini-tablets containing 9 mg ECS were prepared using the direct compression method. The release rates of ECS mini-tablets were controlled by the amount and viscosity grade of hydroxypropylmethyl cellulose incorporated. Gastric retention of ECS mini-tablets after oral administration to rats was visually confirmed using a fluorescence imaging system. Because ECS mini-tablets exhibited size-dependent gastric retention, their gastric retention time was prolonged as the release rate decreased. In the in vivo efficacy study, gastro-retentive dosage forms of ECS did not influence the mucoprotective effect in the immediate irritation model but enhanced the effect in the delayed irritation model compared with ECS suspension. This finding indicates that the duration of the mucoprotective effect of ECS can be extended by the employment of gastro-retentive dosage formulations and provides a rationale for development of ECS gastro-retentive dosage forms.

Drug Release-Modulating Mechanism of Hydrophilic Hydroxypropylmethylcellulose Matrix Tablets: Distribution of Atoms and Carrier and Texture Analysis

Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets.

Preparation of hydroxypropylmethyl cellulose-based porous matrix for gastroretentive delivery of gabapentin using the freeze-drying method

The aims of the present study were to prepare hydroxypropylmethyl cellulose (HPMC)-based porous matrix tablets for gastroretentive drug delivery and to characterize their physicochemical properties. Gabapentin (GBP) was used as a model drug. Paste containing GBP, HPMC and water was molded and freeze-dried to prepare freeze-dried gastroretentive matrix tablet (FD-GRT). In vitro drug release and erosion studies were also performed. Although FD-GRT exhibited porous structure, they had good tablet strength and friability. Density of FD-GRT ranged from 0.402 to 0.509 g/cm3 and thus they could float on the medium surface without any lag time. FD-GRT was remained floated until the entire matrix erosion or end of drug release during in vitro release test. Release behavior of GBP could be modulated by the amount and the viscosity grade of HPMC. However, large amount and high viscosity of HPMC caused trouble in molding prior to freeze-drying. Addition of ethylcellulose could retard the release rate of GBP, with relatively low increase in viscosity of paste. Since pores generated by freeze drying imparted buoyancy for gastric retention to FD-GRT, additional materials for buoyancy was not necessary and FD-GRT had no lag time for buoyancy due to low density. Therefore it could be a promising tool for gastroretentive drug delivery.

Enhanced solubility and dissolution of simvastatin by HPMC-based solid dispersions prepared by hot melt extrusion and spray-drying method

The objective of this study was to use low viscosity grade hydroxypropyl methyl cellulose (Methocel® E3 LV and Methocel® E5 LV) to enhance the solubility and dissolution of poorly water soluble drug simvastatin (SIM). Two different technologies, hot melt extrusion and spray drying were employed. Characterization of hot melt extrudes and spray dried samples was done by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies and scanning electron microscopy. The result of the study showed the conversion of crystalline form drug into amorphous form indicating increase in dissolution rate and solubility of SIM.

Study the effect of formulation variables on drug release from hydrophilic matrix tablets of milnacipran and prediction of in-vivo plasma profile

The objective of this study was to design oral controlled release (CR) matrix tablets of Milnacipran using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, compression force and also the pH of dissolution medium on the in-vitro release of drug. Two viscosity grade of HPMC (15 K and 100 K) were used in the proportion of 50, 100, 150 and 200 mg per CR tablet. In-vitro release rate was characterized using various model dependent approaches and model independent dissolution parameters [T50% and T80% dissolution time, mean dissolution time (MDT), mean residence time (MRT), dissolution efficiency (DE)]. The statistical analysis was performed on all the model independent approaches using student t test and ANOVA. Results were found that as polymer concentration (50 mg to 200 mg) and viscosity (15 K to 100 K) increases, the MDT, MRT, T50% and T80% extended significantly. Drug release rate was found to be significantly different at different hardness. In-vivo human plasma concentration--time profile was predicted from in-vitro release data using convolution method. Predicted human pharmacokinetic parameters shows that the design CR formulation has capability to sustained the plasma drug level of milnacipran.

Formulation in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug

The present study was carried out with an objective of preparation and in vitro evaluation of floating tablets of hydroxypropyl methyl cellulose (HPMC) and polyethylene oxide (PEO) using ranitidine hydrochloride as a model drug. The floating tablets were based on effervescent approach using sodium bicarbonate a gas generating agent. The tablets were prepared by dry granulation method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The effect of sodium bicarbonate and stearic acid on drug release profile and floating properties were also investigated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15MCR and Polyox WSR303. The formulation containing HPMC K15MCR and Polyox WSR303 at the concentration of 13.88% showed 91.2% drug release at the end of 24 hours. Changing the viscosity grade of HPMC from K15MCR to K100MCR had no significant effect on drug release profile. Sodium bicarbonate and stearic acid in combination showed no significant effect on drug release profile. The formulations containing sodium bicarbonate 20 mg per tablet showed desired buoyancy (floating lag time of about 2 minutes and total floating time of >24 hours). The present study shows that polymers like HPMC K15MCR and Polyox WSR303 in combination with sodium bicarbonate as a gas generating agent can be used to develop sustained release floating tablets of ranitidine hydrochloride.

Influence of pH Modifiers and HPMC Viscosity Grades on Nicotine–Magnesium Aluminum Silicate Complex-Loaded Buccal Matrix Tablets

Hydroxypropyl methylcellulose (HPMC) tablets containing nicotine-magnesium aluminum silicate (NCT-MAS) complex particles and pH modifiers, namely, sodium chloride, citric acid, and magnesium hydroxide, were prepared using the direct compression method. The effects of HPMC viscosity grades and pH modifiers on NCT release and permeation of the matrix tablets were examined. The results showed that the higher the viscosity grade of HPMC that was used in the tablets, the lower was the unidirectional NCT release rate found. The unidirectional NCT permeation was not affected by the viscosity grade of HPMC because the NCT diffusion through the mucosal membrane was the rate-limiting step of the permeation. Incorporation of magnesium hydroxide could retard NCT release, whereas the enhancement of unidirectional NCT release was found in the tablets containing citric acid. Citric acid could inhibit NCT permeation due to the formation of protonated NCT in the swollen tablets at an acidic pH. Conversely, the NCT permeation rate increased with the use of magnesium hydroxide as a result of the neutral NCT that formed at a basic microenvironmental pH. The swollen HPMC tablets, with or without pH modifiers, gave sufficient adhesion to the mucosal membrane. Furthermore, the addition of magnesium hydroxide to the matrix tablets was the major factor in controlling buccal delivery of NCT. This study suggests that the NCT-MAS complex-loaded HPMC tablets, which contained magnesium hydroxide, are potential buccal delivery systems of NCT.

Behaviour of HPMC compacts investigated using UV-imaging

The aim of the study was to visualize the behaviour of the hydroxypropyl methylcellulose (HPMC) in a buffer solution using UV imaging. The obtained results were related to rheological measurements in order to gain insight into critical polymer properties affecting drug release. Two viscosity grades of HPMC, 15cP and 50cP, were used. The behaviour of the polymer at the surface of the compact was observed by UV-imaging at 214nm for 90min in a stagnant buffer solution and in presence of flow. Steady shear and oscillatory shear measurements were conducted to determine the rheological characteristics.Three distinctive phases could be detected by real-time UV-imaging of the HPMC; gel formation due to water penetration, further expansion of the gel into solution and finally steady conditions, where a critical polymer concentration that can withstand the shear forces without eroding was observed. The critical concentration corresponded to the rheologically determined gel point, which is the lowest concentration where a 3D-network is obtained. Higher viscosity grade HPMC swelled more rapidly and lead to a thicker gel layer, which was more resistant towards the shear forces due to the applied flow. The results showed that UV imaging is suitable for obtaining both qualitative and quantitative information on polymer behaviour.

Use of propranolol-magnesium aluminium silicate intercalated complexes as drug reservoirs in polymeric matrix tablets

The objective of the present study was to investigate the use of propranolol–magnesium aluminium silicate intercalated complexes as drug reservoirs in hydroxypropylmethylcellulose tablets. The matrix tablets containing the complexes were prepared and characterised with respect to propranolol release and were subsequently compared with those loading propranolol or a propranolol–magnesium aluminium silicate physical mixture. Additionally, the effects of varying viscosity grades of hydroxypropyl methylcellulose, compression pressures and calcium acetate incorporation on the drug release characteristics of the complex-loaded tablets were also examined. The results showed that the complex-loaded tablets have higher tablet hardness than those containing propranolol or a physical mixture. The drug release from the complex-loaded tablets followed a zero-order release kinetic, whereas an anomalous transport was found in the propranolol or physical mixture tablets. The drug release rate of the complex tablet significantly decreased with increasing hydroxypropylmethylcellulose viscosity grade. Increase in the compression pressure caused a decrease in the drug release rate of the tablets. Furthermore, the incorporation of calcium ions could accelerate propranolol release, particularly in acidic medium, because calcium ions could be exchanged with propranolol molecules intercalated in the silicate layers of magnesium aluminium silicate. These findings suggest that propranolol-magnesium aluminium silicate intercalated complexes show strong potential for use as drug reservoirs in matrix tablets intended for modifying drug release.

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet

An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.

Application of percolation theory in the study of an extended release Verapamil hydrochloride formulation

The percolation theory studies the critical points or percolation thresholds of the system, where one component of the system undergoes a geometrical phase transition, starting to connect the whole system. The objective of the present paper was to study the existence of critical points governing the water and drug transport inside hydroxypropylmethylcellulose (HPMC) hydrophilic matrix systems obtained with different polymer viscosity grades. For this purpose, extended release formulations of Verapamil HCl, have been prepared and studied. The percolation theory has been applied for the first time to multi-component hydrophilic matrices. The materials used to prepare the tablets were Verapamil HCl, four different viscosity grades of HPMC, microcrystalline cellulose, lactose, magnesium stearate and colloidal silicon dioxide NF. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. From the point of view of the percolation theory, the optimum concentration for all the studied polymers, to obtain a hydrophilic matrix system for the controlled release of Verapamil HCl is higher than 20% (v/v) HPMC. Above 20% (v/v) HPMC, an infinite cluster of excipient would be formed, ensuring uniform hydration, maintaining integrity of the system and controlling the drug release.

Evaluation of injection moulding as a pharmaceutical technology to produce matrix tablets

The aim of this study was to develop sustained-release matrix tablets by means of injection moulding and to evaluate the influence of process temperature, matrix composition (EC and HPMC concentration) and viscosity grade of ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) on processability and drug release. The drug release data were analyzed to get insight in the release kinetics and mechanism. Formulations containing metoprolol tartrate (30%, model drug), EC with dibutyl sebacate (matrix former and plasticizer) and hydrophilic polymer HPMC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at temperatures ranging from 110 to 140 °C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4 mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw > 20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire matrix, however, some drug clusters were identified.

Development and evaluation of buccoadhesive controlled release tablets of lercanidipine.

The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination. Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride.

Oral Controlled Release Formulations of Rifampicin. Part II: Effect of Formulation Variables and Process Parameters on In Vitro Release

Hydrophilic controlled release matrix tablets of rifampicin, a poorly soluble drug, have been formulated using hydroxypropyl methylcellulose (HPMC) polymer (low, medium, and high viscosity) by direct compression method. Influence of formulation variables and process parameters such as drug:HPMC ratio, viscosity grade of HPMC, drug particle size, and compression force on the formulation characters and drug release has been studied. Our results indicated that the release rate of the drug and the mechanism of release from the HPMC matrices are mainly controlled by the drug:HPMC ratio and viscosity grade of the HPMC. In general, decrease in the drug particle size decreased the drug release. Lower viscosity HPMC polymer was found to be more sensitive to the effect of compression force than the higher viscosity. The formulations were found to be stable and reproducible.

Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as Immediate Release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the . The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.