ritonavir and stearic-acid

Lubricants are important for both preserving the tooling of high-speed tablet presses and attaining quality tablets. Magnesium stearate (MgSt) is most commonly used due to its superior lubrication efficiency; however, it can lead to negative effects on tabletability and dissolution. In this study, we have systematically evaluated two poloxamers, P188 and P407, for their suitability as alternative tablet lubricants. For two excipients with different mechanical properties, i.e., microcrystalline cellulose and lactose, both poloxamers exhibit acceptable lubrication efficiency without negatively impacting tabletability. Compared to 1% MgSt, the performance of 2% of both poloxamers in an experimental tablet formulation of ritonavir led to better lubrication, higher tabletability, and enhanced in vitro drug release. Thus, the use of P188 and P407 as alternative tablet lubricants deserves further evaluations.

Topics: Administration, Oral; Cellulose; Drug Compounding; Drug Liberation; Excipients; Kinetics; Lactose; Lubricants; Poloxamer; Ritonavir; Solubility; Stearic Acids; Tablets

To prepare stearic acid-based lopinavir (LPV) loaded solid lipid nanoparticles (SLNs) using a hybrid design and compare in-vivo performance of optimized formulation with marketed LPV/ritonavir (RTV) coformulation.. LPV SLNs were prepared by hot melt emulsion technique and optimized using Plackett-Burman design and Box-Behnken design. Physical characterization studies were conducted for the optimized SLNs. Comparative oral pharmacokinetic studies and tissue distribution studies of optimized SLNs and LPV/RTV coformulation were done in Wistar rats. In-vitro metabolic stability and intestinal permeability studies for LPV SLNs were undertaken to elucidate the mechanism involved in the pharmacokinetic improvement of LPV.. Optimized SLNs exhibited nanometeric size (223 nm) with high entrapment efficiency (83%). In-vitro drug release study of SLNs showed biphasic sustained release behaviour. Significant increase in oral bioavailability of LPV from LPV SLNs (5 folds) and LPV/RTV coformulation (3.7 folds) was observed as compared with free LPV. LPV SLNs showed better tissue distribution of LPV in HIV reservoirs than LPV/RTV coformulation. In-vitro studies demonstrated that SLNs provided metabolic protection of LPV and were endocytosized during absorption.. SLNs enhanced oral bioavailability and improved distribution profile of LPV to HIV reservoirs and hence could be better alternative to LPV/RTV coformulation.

Topics: Animals; Delayed-Action Preparations; Drug Combinations; Drug Delivery Systems; Drug Stability; Endocytosis; HIV; HIV Protease Inhibitors; Humans; Intestinal Absorption; Lipids; Lopinavir; Male; Nanoparticles; Rats, Wistar; Ritonavir; Stearic Acids; Tissue Distribution