In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200?mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t_10% and t_50% dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer–Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained – with Korsmeyer–Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.     

Role of cellulose ether polymers on ibuprofen release from matrix tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.     

Influence of hydroxypropyl methylcellulose mixture,apparent viscosity,and tablet hardness on drug release using a 2(3) full factorial design

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3-6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000-19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.     

Systematic development of pH-independent controlled release tablets of carvedilol using central composite design and artificial neural networks

The purpose of this study was to apply the optimization method incorporating artificial neural network (ANN) using pH-independent release of weakly basic drug, carvedilol from HPMC-based matrix formulation. Because of weakly basic nature of carvedilol, drug shows pH-dependent solubility. The enteric polymer EUDRAGIT L100 was added formulations to overcome pH-dependent solubility of carvedilol. Effects of the Hydroxypropylmethyl cellulose (HPMC) K4M and EUDRAGIT L100 amount on drug release were investigated. For this purpose 13 kinds of formulations were prepared at three different levels of each variables. The optimization of the formulation was evaluated by using ANN method. Two formulation parameters, the amounts of HPMC K4M and Eudragit L100 at three levels (?1, 0, 1) were selected as independent/input variables. In-vitro dissolution sampling times at twelve different time points were selected as dependent/output variables. By using experimental dissolution results and amount of HPMC K4M and EUDRAGIT L100, percentage of dissolved carvedilol was predicted by ANN. Similarity factor (f₂) between predicted and experimentally observed profile was calculated and f₂ value was found 76.33. This value showed that there was no difference between predicted and experimentally observed drug release profile. As a result of these experiments, it was found that ANNs can be successfully used to optimize controlled release drug delivery systems.     

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.     

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 United States Pharmacopeia (2000). 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.     

Influence of Hydroxypropyl Methylcellulose Mixture,Apparent Viscosity,and Tablet Hardness on Drug Release Using a 23 Full Factorial Design

ABSTRACT

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3–6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000–19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

Kinetic Release of Theophylline from Hydrophilic Swellable Matrices

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg ± 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.     

Kinetic Release of Theophylline from Hydrophilic Swellable Matrices

The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg ± 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.     

Sustained Release Tablet Formulation for a New Iron Chelator

Abstract

Sustained release tablet formulations for a new orally active iron chelator (1, 2, dimethyl-3-hydroxy-pyrid-4-one, DMHP or L1) have been developed. Coprecipitates containing DMHP and polymer were prepared and compressed into matrix-type tablets. The dissolution profiles as a function of (1) the type of polymer, and (2) polymer content, were determined. Both Eudragit types (RLPM and RSPM) and all hydroxypropylmethylcellulose (HPMC) grades (E4M, E10M, and K4M) exhibited significant sustained release activity. Above a certain ratio, increase in the polymer concentration did not provide any further decrease in the release rates. All grades of HPMC and both Eudragit RSPM and RLPM showed non-Fickian release kinetics. The role of HPMC and Eudragits in the formulation of a sustained release tablet of a water soluble drug is demonstrated.     

Sustained Release Tablet Formulation for a New Iron Chelator

Sustained release tablet formulations for a new orally active iron chelator (1, 2, dimethyl-3-hydroxy-pyrid-4-one, DMHP or L1) have been developed. Coprecipitates containing DMHP and polymer were prepared and compressed into matrix-type tablets. The dissolution profiles as a function of (1) the type of polymer, and (2) polymer content, were determined. Both Eudragit types (RLPM and RSPM) and all hydroxypropylmethylcellulose (HPMC) grades (E4M, E10M, and K4M) exhibited significant sustained release activity. Above a certain ratio, increase in the polymer concentration did not provide any further decrease in the release rates. All grades of HPMC and both Eudragit RSPM and RLPM showed non-Fickian release kinetics. The role of HPMC and Eudragits in the formulation of a sustained release tablet of a water soluble drug is demonstrated.     

Preparation and characterization and release properties of Eudragit RS based ibuprofen pellets prepared by extrusion spheronization: effect of binder type and concentration

Objective: The effects of type and concentration of binding agent on properties of Eudragit RS based pellets were studied.

Materials and methods: Pellets containing ibuprofen (60%), Eudragit RS (30%), Avicel (10%) were prepared by extrusion spheronization. PVP K30, PVP K90, HPMC 6cp, HPMC K100LV or HPMC K4M were used as binders in concentrations of 2, 4 or 6% based on the total weight of formulation. The process efficiency, pellet shape, size distribution, crushing strength, elastic modulus and drug release were examined. The effect of curing on pellet properties was also investigated.

Results: The process of extrusion spheronization became difficult with increase in binder viscosity and/or concentration. An increase in binder viscosity and/or concentration resulted in reduction in the yield of pellets, wider particle size distribution and departure from spherical shape especially in the case of HPMC binder. The crushing strength and elastic modulus of pellets decreased with increase in PVPs concentration. However this was not the case for pellets containing HPMCs. Drug release rate increased as the concentration of binder increased. Pellets containing 2%w/w of PVP K30 showed the slowest release rate. For those pellets with brittle nature, curing changed the behavior of pellet under mechanical test to plastic deformation. Yield point and elastic modulus of all formulations decreased after curing. Curing decreased the drug release rate.

Conclusion: Binder type and concentration significantly affected the properties of pellets. For production of sustained release ibuprofen Eudragit RS based pellets lower viscosity binders (PVP K30) with concentrations less than 4%w/w was optimum.     

The effect of pH,buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel^® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol^® HD5 ATO). The two formulations attained release profiles of QF over 24?h similar to that of Seroquel^® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel^® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro–in vivo correlations.     

Tailoring the Release Rates of Fluconazole Using Solid Dispersions in Polymer Blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Tailoring the release rates of fluconazole using solid dispersions in polymer blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Production of extended release mini-tablets using directly compressible grades of HPMC

Context: Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company.

Objective: To compare the properties of HPMC DC (METHOCEL? K4M and K100M) with regular (REG) HPMC grades.

Method: Particle size distribution and flowability of HPMC REG and DC were evaluated. 3?mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2–4?kN and speeds of 5, 10, 15 or 20?rpm. Mini-tablets containing HPMC REG were produced manually.

Results and discussion: The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79–4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles.

Conclusions: Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.     

New sustained release of Zidovudine Matrix tablets − cytotoxicity toward Caco-2 cells

Objective: The aim of this study was to adjust the zidovudine (AZT) release from solid tablets to an ideal profile, by developing matrices comprising swellable polymers with nonswellable ones.

Methods: Directly compressed matrices comprised different ratios of hydroxypropylmethylcellulose K15M and K100M, ethylcellulose, and methacrylic acid (Eudragit^® RS PO and Eudragit^® RL PO) were prepared. Technological characterization and evaluation of the in vitro release behavior were carried out. Cell density and viability following drug exposure were evaluated by the SRB method, for the Caco-2 line, while cell morphology was assessed upon Trypan blue staining.

Results: A specific formulation containing 5% of each excipient ? HPMC K15M, HPMC K100M, Eudragit^® RS PO, and Eudragit^® RL PO ? was found to yield the best release profile. Application of the Korsmeyer–Peppas model to the dissolution profile evidenced that a non-Fickian (anomalous) transport is involved in the drug release. Regarding the influence of the tablets’ composition on the drug’s cytotoxic effect toward the Caco-2 cell line, a reduction of cell biomass (0–15%) was verified for the distinct AZT formulations tested, F19 having displayed the highest cytotoxicity, after 24 and 48?h of incubation. Additionally, a high reversibility of the AZT effect was observed.

Conclusions: The results showed that the simultaneous application of both hydrophilic and hydrophobic polymers can modulate the drug release process, leading to an improved efficacy and patient compliance. All AZT formulations studied were found to be cytotoxic against Caco-2 cells, F19 being the most effective one.     

Preparation and in Vitro evaluation of mefenamic Acid Sustained Release Beads

Abstract

Sustained release beads of mefenamic acid were prepared by a capillary method using cellulose acetate phthalate, surfactants (Tween 80 and Span 80), and polymers (K 100 M Methocel and K 100 LV Methocel). These beads were then formulated into capsule dosage form. The beads did not disintegrate in simulated gastric fluid; however, they disintegrated in simulated intestinal fluid. The dissolution profiles of mefenamic acid beads and capsule dosage form were conducted in phosphate buffer (pH 7.2) at 37° C. The beads containing Span 80 and a mixture of K 100 M and A 4 M Methocel resulted in prolonged drug release. The formulations prepared with Tween 80 and K 100 LV Methocel released over 90% of the drug in 2 hours indicating no sustained release properties. The beads in capsule dosage form yielded slower dissolution profiles compared to the beads alone. Aging for six months had no effect on dissolution of mefenamic acid beads. The release of mefenamic acid seems to be combination of diffusion and leaching. The release of mefenamic acid from beads can be modified by varying the polymer composition and their concentration.