Purpose: Raloxifene HCl (RLX), a practically insoluble drug used in the treatment of osteoporosis in post-menopausal women; was modified at its molecular level to enhance its solubility using co-amorphous technology.
Methods: In this study, RLX was co-amorphized with Quercetin (QCT; a nutraceutical flavonoid) using solvent evaporation (SE), quench cooling (QC), and ball milling (BM) techniques. The prepared co-amorphous systems (CAMs) were characterized using XRD, DSC, and FT-IR. For the simultaneous analysis of RLX and QCT, an RP-HPLC method was developed to quantify the drugs in the prepared systems. Behavior in aqueous media was investigated by studying amorphous and equilibrium solubility, and drug release of RLX using USP phosphate buffer pH 6.8.
Results: Solvent evaporation (RQ(SE)) was able to produce a homogeneous system, where quench cooling showed thermal degradation of the drug, and ball milling was not able to amorphize the blend. From the DSC results, it was found that RQ(SE) was able to increase the glass transition temperature by 40 °C. It was observed that the solubility of RLX reduced, as RLX formed phosphate aggregates in the buffer media which further formed complexes with QCT; this was determined by investigating the residual particles from solubility studies. Though the solubility was reduced, drug release of RQ(SE) exhibited improvement in concentration by 2.3 times.
Conclusions: RQ(SE) formed a stable CAM; though the solubility of RLX in presence of QCT reduced, from the drug release study, it was apparent that the co-amorphous technique improved the concentration of RLX.
Keywords: Quercetin; Raloxifene HCl; amorphous solid dispersions; co-amorphous systems; phosphate aggregates; weekly acidic ionizable drugs; weekly basic drugs.