Lumefantrine solid dispersions with piperine for the enhancement of solubility, bioavailability and anti-parasite activity.

Crystallinity and P-glycoprotein (P-gp) mediated efflux of drugs with low aqueous solubility collaboratively contributes to erratic absorption resulting in low/variable bioavailability. Herein, the amorphous solid dispersions (SD) of lumefantrine (LUMF) containing piperine (PIP), a P-gp and CYP3A4 inhibitor, were formulated with Soluplus (Sol), Klucel (Klu) and Lutrol F68 (Lut), polymeric carriers, to improve solubility and bioavailability of LUMF following oral administration. The LUMF-PIP-SD prepared with Sol exhibited higher aqueous solubility of LUMF in concentration dependent manner and LUMF-PIP-Sol demonstrating maximum aqueous LUMF solubility were characterized by DSC, FTIR and XRD. The DSC thermogram and XRD diffractogram of LUMF-PIP-SD confirmed the loss of crystallinity of LUMF ensuing improved dissolution while possible interaction of LUMF with PIP and /or Sol was evident in FTIR spectrum. DSC and dissolution studies confirmed the stability for LUMF-PIP-Sol SD stored for 90 days under stressed conditions of humidity and temperature. An in situ single-pass intestinal perfusion study in rats indicated 2.2-fold increase in intestinal permeation of LUMF co-administered with PIP. Improved bioavailability of LUMF was evidenced by increased AUC0-∞ and Cmax for LUMF in SD compared to alone LUMF or LUMF with PIP. Peter's four-day suppressive test indicated improved antimalarial activity for LUMF-PIP-Sol SD. Overall, the data suggest that the SD of LUMF incorporated with P-gp inhibitor PIP, improves the bioavailability as well as antimalarial efficacy of LUMF.

Trimethyl chitosan and its applications in drug delivery.

Chitosan, a polymer obtained by deacetylation of chitin is widely studied for its pharmaceutical and nonpharmaceutical applications. Recommendations about uses of this polymer although could not be always realized due to limited solubility. Chitosan, for example, has been extensively evaluated for its mucoadhesive and absorption enhancement properties. The positive charge on the chitosan molecule gained by acidic environment in which it is soluble seems to be important for absorption enhancement. However chitosan is not soluble in medium except below pH 5.6. This limits its use as permeation enhancer in body compartments where pH is high. In this regard there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values. Trimethylation of chitosan is an effort in this direction. Despite the abundance of the research related to trimethyl chitosan (TMC), the overview of the topic is not available. Hence an attempt is made in this review to cover the recent findings pertaining to synthesis, characterization and applications of TMC especially in pharmaceutical field. TMC has been synthesized by different ways and characterized by FTIR, NMR, DSC etc. This quaternized derivative of chitosan possesses a positive charge and is soluble over a wide range of pH. TMC, being a derivative of cationic polymer enriched with positive charge shows better mucoadhesive, permeation enhancement, drug delivery and DNA delivery properties. TMC can be further derivitized or grafted for modulating properties as solubility, cytotoxicity or cell recognition ability. Apart from these applications, TMC itself and its derivatives exhibit antimicrobial properties also. Quaternization of chitosan not only with methyl group but higher group as ethyl or along with spacer or quaternization of modified chitosan can be of interest too.