Insights into the Role of Compendial/Biorelevant Media on the Supersaturation Behaviour of Drug Combination (Drug-Drug Interaction) and Precipitation Inhibition by Polymers.

Combination drug therapy (CDT) plays an immense role in the treatment of various diseases such as malaria, hypertension, cancer, HIV-AIDS, helminthiasis, and many more. However, in vitro drug-drug interaction (DDI) is not well reported for better efficacy of CDT. In DDI one drug may enhance the precipitation of other drugs thereby reducing the advantage of CDT. Herein, we report DDI in terms of in vitro precipitation of drugs with albendazole and mebendazole. This may be the first report to propensate the possibility of either drug precipitation in the combination. These drugs are categorized into BCS class II weak base and hence have tendency to precipitate in the gastrointestinal tract. The objective of this study is to find precipitation of drug combinations in different compendial and biorelevant media (deionized water, phosphate buffer pH 6.8, FaSSIF, and FeSSIF) and screening of the polymers for precipitation inhibition. Nine polymers were investigated at three different concentrations in terms of their drug-polymer solubility, in vitro precipitation behavior, induction time, SHC, and droplet size. Although, all the polymers inhibit the precipitation of drugs, the extent of precipitation inhibition for Soluplus is high. The obtained drug-polymer precipitates were filtered, dried, and analyzed for amorphous/partial amorphous form using polarised light microscopy (PLM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). The drug-polymer interaction was examined using Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) revealing the effect of polymers on drug precipitation. These insights may further be used in the formulation of CDT for helminthiasis management.