Formulation and characterization of an expandable, gastroretentive system of carvedilol phosphate by 32 factorial...

A 3(2) full factorial design was employed for the formulation and characterization of an expandable, gastroretentive sustained-release formulation of carvedilol phosphate to maintain drug levels within a desired range, reduce dosing frequency, and to increase the bioavailability of drug. Due to its pH-dependent solubility, it is necessary to improve the concentration of the drug in the stomach so as to improve its absorption there and in the upper part of the small intestine. In the present study, an attempt has been made to improve drug concentration in the stomach by preparing gastroretentive, swellable, matrix-based sustained release tablets of carvedilol phosphate that due to their size would be retained in the upper part of gastrointestinal tract.

Carvedilol phosphate (CP) exhibits typical solubility behavior in neutral or alkaline media-that is, the solubility of CP is maximum in the upper part of the gastrointestinal tract (GIT). Improvement in the concentration of the drug in solution at the site of absorption (i.e., in the upper part of the GIT) is essential to improve absorption because CP has pH-dependent solubility. These gastroretentive dosage forms are easily swallowed and reach a significantly larger size in the stomach due to swelling, achieve a size more than the diameter of the pylorus, and are not able to pass through the pylorus, thus causing prolongation of gastric residence time. A statistical optimization design is a powerful, efficient, and systematic tool that shortens the time required for the development of pharmaceutical dosage forms. This design was used for optimizing the concentration of polymer so as to achieve the desired swelling of the dosage form for retention in the upper part of the GIT. In this design, two variables were evaluated, each at three levels, and experimental trials were performed using all nine possible combinations. In the present investigation, the amounts of polyethylene oxide (PEO) K12N and hydroxypropyl methylcellulose (HPMC) K100M were selected as independent variables.