TY - JOUR AU - Misic, Zdravka AU - Šišak Jung, Dubravka AU - Sydow, Georg AU - Kuentz, Martin PY - 2014/06/25 TI - Understanding interactions of oleic acid with basic drugs in solid lipids on different biopharmaceutical levels JF - Journal of Excipients and Food Chemicals; Vol 5 No 2 (2014) KW - drug-excipient interactions, basic drugs, oleic acid, supersaturation, precipitation kinetics, solid lipid-based systems N2 - Recently, the impact of intestinal supersaturation on absorption of poorly water-soluble drugs has raised much interest among researchers. A focus has been mostly to study excipient effects on maintenance of drug supersaturation. The aim of the present study was to better understand the effects of drug-excipient interactions on the level of the anhydrous formulation, upon dispersion in simple buffer media and, in particular, regarding precipitation kinetics. A solid lipid-based formulation comprising PEG-32 stearate and oleic acid (OA) (8:2 w/w) was developed as a model. Loratadine (pK a = 4.33) and carvedilol (pK a = 8.74) were chosen as basic drugs. UV/FTIR spectroscopy and viscometry were used to characterize drug-OA molecular interactions in solution, while solid formulations were studied using x-ray diffraction, thermal analysis and van’t Hoff solubility-temperature plots. Precipitation kinetics of drug formulations was real-time monitored in phosphate buffer (pH = 6.5) by focused beam reflectance measurements. It was found that the addition of OA in the formulations resulted in substantial drug solubility increase. Although the drug-OA interactions appeared to be partially lost upon formulation dispersion, the extent of precipitation was markedly lowered compared to the formulations without OA. A Precipitation number ( P nc ) was introduced as a ratio of a relevant residence time of drug in the gastrointestinal tract (GIT) to the induction time (the onset time of crystalline precipitation). Without OA, P nc was already taking critical values (>1), while the anhydrous formulation was still below saturation for both model drugs. Interestingly, the addition of OA resulted in amorphous instead of crystalline precipitates, which is advantageous for drug re-dissolution and absorption. In conclusion, this study provides an improved understanding of OA and basic drug interactions on different levels of in vitro performance for more rational oral formulation development. UR - https://ojs.abo.fi/ojs/index.php/jefc/article/view/524