Formulation and optimization of controlled release mucoadhesive tablets of atenolol using response surface methodology

Abstract

The aim of the current study was to design oral controlled release mucoadhesive compressed hydrophilic matrices of atenolol and to optimize the drug release profile and bioadhesion using response surface methodology. Tablets were prepared by direct compression and evaluated for bioadhesive strength and in vitro dissolution parameters. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile and bioadhesive strength. Carbopol 934P and sodium carboxymethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Compressed matrices exhibited non-Fickian drug release kinetics approaching zero-order, as the value of release rate exponent (n) varied between 0.6672 and 0.8646, resulting in regulated and complete release until 24 hours. Both the polymers had significant effect on the bioadhesive strength of the tablets, measured as force of detachment against porcine gastric mucosa (P < .001). Polynomial mathematical models, generated for various response variables using multiple linear regression analysis, were found to be statistically significant (P < .01). Validation of optimization study, performed using 8 confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error (± SD) as −0.0072 ± 1.087. Besides unraveling the effect of the 2 factors on the various response variables, the study helped in finding the optimum formulation with excellent bioadhesive strength and controlled release.

Formulation development of oral controlled release tablets of hydralazine: Optimization of drug release and bioadhesive characteristics

“…Drug release rate curves (Fig. 1, inset) of all the formulations portray an initial burst release of the drug, characteristic of most hydrophilic matrices (3,14,22). Summary of the drug release parameters (Table III) shows that the value of n varies from 0.4653 to 0.6618, distinctly delineating the non-Fickian release behaviour of all formulations.…”

“…Bioadhesion studies were conducted employing a slightly modified version of an in-house fabricated bioadhesion assembly (3,14). Porcine gastric mucosa was used as the model membrane.…”

Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential

“…Also this approach is known to provide a depth of understanding and ability to explore and defend the ranges for varied formulation and processing factors. Central composite design (CCD), in this regard, has been frequently employed for the optimization of the SEDDS formulation (Singh & Ahuja, 2002;Singh et al, 2006). Thus, the present investigation aims at developing SEDDS of carvedilol employing systematic DoE for enhancement of its dissolution and bypassing the first-pass effect, resulting consequently in an increased bioavailability.…”

Design and Development of Novel Mucoadhesive Gastroretentive Formulation of Glipizide

“…The balance was kept in this position for 3 minutes after which weights were added slowly to the right pan until the film separated from the mucosal surface. The excess weight on the pan (total weight minus 5 g) is the bio adhesive strength required to separate the film from the mucosa [26][27][28] . The force of adhesion was calculated using the formula: Determination of drug content Accurately cited 2 cm × 2 cm diameter of the films was taken and dissolved in methanol and constant volume of solvent.…”