Search

The purpose of this study was development of diclofenac sodium extended release compressed matrix pellets and optimization using Generalized Regression Neural Network (GRNN). According to Central Composite Design (CCD), ten formulations of diclofenac sodium matrix tablets were prepared. Extended release of diclofenac sodium was accomplished using Carbopol 71G as matrix substance. The process of direct pelletisation and subsequently compression of the pellets into MUPS tablets was applied in order to investigate a different approach in formulation of matrix systems and to achieve more control of the process factors over the principal response--the release of the drug. The investigated factors were X1-the percentage of polymer Carbopol 71 G and X2-crushing strength of the MUPS tablet. In vitro dissolution time profiles at 5 different sampling times were chosen as responses. Results of drug release studies indicate that drug release rates vary between different formulations, with a range of 1 hour to 8 hours of dissolution. The most important impact on the drug release has factor X1the percentage of polymer Carbopol 71 G. The purpose of the applied GRNN was to model the effects of these two causal factors on the in vitro release profile of the diclofenac sodium from compressed matrix pellets. The aim of the study was to optimize drug release in manner which enables following in vitro release of diclofenac sodium during 8 hours in phosphate buffer: 1 h: 15-40%, 2 h: 25-60%, 4 h: 35-75%, 8 h: >70%.

Using mixture experimental design, the effect of carbomer (Carbopol((R)) 971P NF) and hydroxypropylmethylcellulose (Methocel((R)) K100M or Methocel((R)) K4M) combination on the release profile and on the mechanism of drug liberation from matrix tablet was investigated. The numerical optimization procedure was also applied to establish and obtain formulation with desired drug release. The amount of TP released, release rate and mechanism varied with carbomer ratio in total matrix and HPMC viscosity. Increasing carbomer fractions led to a decrease in drug release. Anomalous diffusion was found in all matrices containing carbomer, while Case - II transport was predominant for tablet based on HPMC only. The predicted and obtained profiles for optimized formulations showed similarity. Those results indicate that Simplex Lattice Mixture experimental design and numerical optimization procedure can be applied during development to obtain sustained release matrix formulation with desired release profile.

The purpose of this study was to investigate the effect of various in vitro test conditions, on the release properties of theophylline (TP) from aminophylline (AP) matrices based on different hydroxypropylmethylcellulose (HPMC) ratio and viscosity grades. The general full factorial experimental design 3 x 3 x 3 was used, based on three independent variables: applied in vitro test (X1), HPMC/drug ratio (X2) and polymer viscosity grade (X3). The drug release percent at 2h (Y(2h)), 4h (Y(4h)) and 8 h (Y(8h)) and time for 50% of TP release from matrices (Y(T50%)) were response variables. Three in vitro tests were used: test 1 and test 4 (theophylline extended-release capsules, USP 30) and half-change method. According to factorial design analyses, in vitro test was the most significant factor influencing mechanism and amount of drug release. For half change method erosion was the predominant mechanism indicating case - II transport, while for test 1 the release mechanism were followed by both diffusion and erosion. The lowest release exponent n values, obtained from Ritger-Pepass equation, for test 4 indicate diffusion process inclining from Fickian diffusion to anomalous transport. Therefore, it is in the stage of development, useful to consider the influence of various in vitro test conditions on the formulation, in order to choose an optimal test for the purpose of future drug release examination.