Fabrication and In Vitro Evaluation of Febuxostat Tablet for Obtaining Biphasic Drug Release Profile

The primary aim of the present investigation was to adopt the concept of quality by design (QbD) for developing Febuxostat matrix tablets containing a novel combination of polyethylene oxide (PEO), pre-gelatinized starch (PGS) and lactose for obtaining biphasic drug release.

Febuxostat-containing matrix tablets were prepared by direct compression using 32 full factorial designs. The tablets were prepared with varying amounts of PEO WSR 301 to PGS and lactose to obtain the desired release pattern. The chosen responses were cumulative % drug released at 1, 6 and 12 hours. The evaluation of tablets was done for pre and post-compressional parameters. Compared with the marketed tablet, the optimized formulations were selected based on in vitro drug release. Dose dumping was checked in the dissolution medium containing up to 40% alcohol.

The results of the dissolution study indicated that the batch containing a 1:1 ratio of PEO WSR 301 and PGS (15 mg each) and 20 mg of Lactose showed fast initial drug release to imitate the pharmacological action followed by sustained drug release effect. The use of Lactose facilitated immediate drug release, while PEO WSR 301 and PGS exhibited the opposite effect on cumulative drug release. The results of the 3² Factorial design revealed that the concentration of Lactose is a critical parameter. Dose dumping was not observed in the alcoholic dissolution medium. Kinetic equations were fitted to the dissolution data after 1 hour of the dissolution study.

The type (soluble or swellable) and the concentration of excipients (low or high) dictate the tablets' drug release. The study's outcome revealed that the most critical material attribute is the amount of lactose. The novel combination of PEO, PGS and lactose can bypass existing patents and give more industrial applicability.