Development and optimization of osmotically controlled drug delivery system for poorly aqueous soluble diacerein to improve its bioavailability

Abstract

In an attempt to improve the low oral bioavailability of Diacerein (DCN), the combination of a ternary solid dispersion and an asymmetric osmotic pump system had been designed to enhance solubility and to control DCN delivery. Ternary DCN solid dispersion was prepared by melting fusion method using surfactant polymers, and carrier (Pluronic^® PF127, Solutol^® HS15, and PEG 35 K) and this DCN solid dispersion powder with the proper amount of excipients were compressed and coated with Opadry^®CA to develop a Semi-Permeable and Asymmetric Osmotic Pump tablets. The ternary DCN solid dispersion by using surfactant polymers (Pluronic^® F127 and Solutol^® HS 15) with a ratio of 1:1 was displayed market significant improvement in saturated solubility (70.2 ± 4.14 µg/ml) and fast dissolution rate (Q_60min = 79.28 ± 3.1% and IDR_5 min = 5.25 ± 0.19 ml/min) in comparison to pure DCN. Moreover, the optimized asymmetric osmotic pump tablet with following parameters; 3% w/v Opadry^® CA coat concentration, 1% w/w HPMC E15 gelling polymer and 35.8%w/w NaCl Osmogen concentration, was displayed control release of DCN at zero-order kinetic (R² = 0.977) for up to 24 h(s). The in-vivo study conducted on rabbits was revealed a significant enhancement in the bioavailability of the optimized osmotic pump (28.84 ± 3.32 ng.hr/ml) compared to DCN dispersion (10.39 ± 1.45 ng.hr/ml). In conclusion, the approach of enhancing solubility and wet-ability in accompany with optimized asymmetric osmotic pump system could serve as a promising delivery system and a way to improve the bioavailability of poorly aqueous soluble drugs.

Keywords:

• Osmotic pump
• ternary solid dispersion
• rotatable central composite design
• zero order kinetic
• bioavailability

Acknowledgments

The authors would like to extend their appreciation to the pharmaceutical department at the faculty of pharmacy, Cairo University, CAIRO, EGYPT, for helping in this study.

Ethical approval

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the Research Ethics Committee, Faculty of Pharmacy, Cairo University, Egypt (Serial No. PI (1651)).

Disclosure statement

Authors, Magdy I. Mohamed, Abdulaziz M. Al-Mahallawi, Sami M. Awadalla, declare that they have no conflict of interest and did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.