(T1530-09-51) Formulation and Characterization of Quetiapine Fumarate Floating Bioadhesive Tablets Using TSMG

Purpose: The purpose of this study was to develop Quetiapine Fumarate (QF) gastroretentive tablets using the Twin Screw Melt Granulation (TSMG) technology, which combines a floating and mucoadhesive approach. The aim was to improve the absorption by prolonging its gastric residence time. QF has a plasma half-life of 6 hours exhibits high solubility in acidic pH, and is slightly soluble in alkaline pH.

Methods: Gastro-retentive floating and mucoadhesive QF tablets were prepared using the TSMG technology with an 11 mm co-rotating extruder. The impact of polymer concentration and viscosity grades of HPMC on the floating ability, mucoadhesion, and drug release profile was investigated. The produced granules were analyzed for flow properties and characterized using Differential Scanning Calorimetry (DSC). The tablets prepared using granules obtained from the Process 11 extruder were evaluated for content uniformity, weight variation, hardness, and friability for the lead formulation, floating time, dissolution studies, and mucoadhesive test for all the formulations.

Results: Formulations with higher polymer viscosity grades (HPMC K35M and HPMC K15M), exhibited slower drug release due to slower gelation. On the other hand, formulations with lower polymer concentration (10% w/w) failed to achieve floating behavior due to limited gelling ability. The lead formulation containing 30% HPMC K4M met the USP dissolution test 11 specifications for QF extended-release tablets, demonstrating sustained drug release over 16 hours. The study indicates that HPMC can produce a sustained drug release pattern due to its ability to hydrate and form a gel-like structure, imparting floating behavior to the QF tablets. The formulations with 20-30% polymer exhibited 16 hours of floating time without lag time and demonstrated mucoadhesive properties. In contrast, tablets prepared using the direct compression method failed to exhibit the desired release profile as per the USP specification for QF extended-release tablets. This highlights the importance of the TSMG technology, combined with the appropriate selection of HPMC viscosity grade and concentration, in enabling the development of gastro-retentive floating QF tablets with sustained drug release, floating behavior, and mucoadhesive properties, meeting the USP dissolution specifications for extended-release formulations.

Conclusion: Preparing QF gastroretentive floating and mucoadhesive tablets using the TSMG technology has significant value as it is a continuous manufacturing process. The TSMG approach, which combines a floating and mucoadhesive mechanism, was successful in improving the absorption of QF by prolonging its gastric residence time (floating), as evidenced by the in-vitro dissolution studies.

References: 1. Tripathi, J., Thapa, P., Maharjan, R., & Jeong, S. H. (2019). Current State and Future Perspectives on Gastroretentive Drug Delivery System s. Pharmaceutics, 11(4). https://doi.org/10.3390/pharmaceutics11040193
2. Mandal, U. K., Chatterjee, B., & Senjoti, F. G. (2016). Gastro-retentive drug delivery systems and their in vivo success: A recent update. Asi an Journal of Pharmaceutical Sciences, 11(5), 575-584. https://doi.org/10.1016/j.ajps.2016.04.007

Figure 1. Floating profile and Bioadhesive strength of all formulations

Figure 2. In-Vitro drug release study of F1-F7 in 0.1N HCl

Figure 3. A. The immediate floating of the tablet, B. After 1hr, and C. after 16 hours