Development of Doxazosin mesylate liquisolid system for improved manufacturing processability and bioavailability: in vitro and in vivo evaluation for tailored hypertension treatment approach with modified dissolution rates

Abstract

In the present research, an attempt was made to optimize the blends of different carriers Neusiln US2, Avicel PH101, and Fujicalin SG by individually blending with each of coating materials Aerosil 200 and Syloid 244 FP that were proposed to contribute to a modified drug dissolution rates of Doxazosin mesylate (DX) through a liquisolid polymer matrix system. The liquisolid formulations were prepared using selected solvent, carriers, and coats by varying drug to polymer ratios. Further formulations were investigated for pre-compression processability by Heckel plot analysis, elastic recovery studies, and post-compression characteristics. In case of carriers, compared to Avicel PH101 highest flowable values (ф) were observed for Neusilin US2 and Fujicalin SG whereas, for coat these values were highest for Aerosil 200 than Sylloid 244 FP. Liquisolid compact with Fujicalin SG and Aerosil 200 exhibited fast release (FR) of 78% in 20 minutes. The liquisolid compact with Neusilin US2 and Syloid 244 FP exhibited prolonged release (PR) of 60% in 240 minutes. DSC and XRD analysis showed loss of DX crystallinity which was confirmed by SEM analysis indicating DX detention within the liquisolid system, in a molecularly dispersed solubilized form. The in vivo studies of DX liquisolid FR formulation exhibited 1.89 fold increase in the oral bioavailability which was 1.69 fold for DX PR formulation compared to pure DX which demonstrated a promising tailored hypertension treatment approach.

Graphical abstract

Keywords:

• Liquisolid technique
• carrier polymer
• coating polymer
• modified dissolution rates
• bioavailability

Acknowledgments

The authors would like to thank Management and all stakeholder of Bharati Vidyapeeth College of Pharmacy, Kolhapur, for provision of facilities; Grace Materials Technologies, Columbia, USA, for providing a gift sample of Syloid 244 FP; and Gangwal Chemicals, Mumbai, for providing a free samples of Neusilin US2 and Fujicalin SG.

Disclosure statement

No conflicts of interest have been disclosed by the authors

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.