Optimization of acyclovir oral tablets based on gastroretention technology: Factorial design analysis and physicochemical characterization studies

Abstract

The purpose of this research was to prepare a floating drug delivery system of acyclovir. Floating matrix tablets of acyclovir were developed to prolong gastric residence time and increase its bioavailability. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose 4000, Compritol 888. Sodium bicarbonate was used as a gas-generating agent. A 3² factorial design using the Design Expert Software (version 7.1.6) was applied to optimize the drug release profile systematically. The amounts of hydroxypropylmethylcellulose 4000 (X₁) and Compritol 888 (X₂) were selected as independent variables and the percentage drug released in 1 (Q₁), 6 (Q₆), and 12 (Q₁₂) h as dependent variables. The results of factorial design indicated that a high level of both hydroxypropylmethylcellulose 4000 (X₁) and Compritol 888 (X₂) favors the preparation of floating controlled-release of acyclovir tablets. Also, a good correlation was observed between predicted and actual values of the dependent variables chosen for the study. By fitting the data into zero-order, first-order, and Higuchi models, we concluded that the release followed Higuchi diffusion kinetics. Storage of the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in drug release profiles and buoyancy of the floating tablets. We can conclude that a combination of hydroxypropylmethylcellulose 4000, Compritol 888, and sodium bicarbonate can be used to increase the gastric residence time of the dosage form up to 12 h. These floating tablets seem to be a promising gastroretentive drug delivery system.

Keywords::

• Acyclovir
• floating time
• gastroretentive
• factorial design
• HPMC
• Compritol
• bioavailability