Patient-friendly extemporaneous formulation of bisoprolol: application to stability and bioavailability studies

Drug Deliv Transl Res. 2022 Oct 3. doi: 10.1007/s13346-022-01239-x. Online ahead of print.

Abstract

Community and hospital pharmacists always face the challenge to prepare oral liquid extemporaneous formulations to fit the needs of a specific patient population when commercial forms or the required strength is unavailable. This study was performed to prepare a stable patient-friendly oral liquid extemporaneous formulation of bisoprolol. Eight different extemporaneous formulations were prepared using various suspending agent(s). The in vitro dissolution of all extemporaneous formulations was examined. A comprehensive accelerated stability study was carried out to evaluate the adequate beyond-use date of the most optimized extemporaneous formulation. A validated ultra-performance liquid chromatography method was used for the analysis and quantification of bisoprolol in the accelerated stability and bioavailability studies. A group of eight healthy volunteers was enrolled in a two-way cross-over experimental design to study the bioavailability of the most optimized extemporaneous formulation. The pharmacokinetic parameters of bisoprolol were estimated. Extemporaneous suspension containing 0.5% w/v xanthan gum was easily prepared with a simple, natural, safe, sugar-free excipients. It achieved the best dissolution behavior among other extemporaneous suspensions. It was an easily pourable viscous suspension with no sedimentation. At least 98% of the initial concentration of bisoprolol remained throughout the 6-month study period in the selected suspension regardless of the storage conditions. There was no perceptible change in color, odor, or taste, and no noticeable microbial growth was observed in any sample. The selected formulation was bioequivalent to the commercial tablet in terms of the rate and extent of absorption. This research may be of great help during development of appropriate extemporaneous formulation of bisoprolol fumarate. The simple preparation method could be utilized to draw up a standard operating procedure (SOP) easy to use by different types of pharmacy settings.

Keywords: Bioavailability; Bisoprolol; Extemporaneous suspension; SOP; Stability.