Menthol augmented niosomes for enhanced intestinal absorption of lopinavir.

Lopinavir is effective in treatment of HIV infection but experiences low oral bioavailability due to poor solubility, pre-systemic metabolism, and P-gp intestinal efflux. Co-processing with menthol enhanced its dissolution and intestinal permeability. Niosomes comprising Span 60, cholesterol, and poloxamer 407 were formulated in absence and presence of menthol. These were evaluated for size, morphology, entrapment efficiency (EE%), lopinavir release, and intestinal absorption. The later employed in situ rabbit intestinal absorption model. Niosomes were spherical with vesicle size of 140.2 ± 23 and 148.2 ± 27 nm for standard and menthol containing niosomes, respectively. The EE% values were 94.4% and 96.3% for both formulations, respectively. Niosomes underwent slow release during the time course of absorption with menthol hastening lopinavir release, but the release did not exceed 9%. Niosmoal encapsulation enhanced lopinavir intestinal absorption compared with drug solution. This was reflected from the fraction absorbed from duodenum, which was 24.15%, 73.09%, and 83.23% for solution, standard niosomes and menthol containing vesicles, respectively. These values were 34.32%, 80.8%, and 86.56% for the same formulations in case of jejuno-ileum. Lopinavir absorption from niosomes did not depend on release supporting intact vesicle absorption. The study introduced menthol containing niosomes as carriers for enhanced lopinavir intestinal absorption.

Lopinavir-menthol co-crystals for enhanced dissolution rate and intestinal absorption.

Lopinavir is an antiretroviral, antiparasitic agent and recently utilized in treatment of COVID-19. Unfortunately, lopinavir exhibited poor oral bioavailability due to poor dissolution, extensive pre-systemic metabolism, and significant P-glycoprotein intestinal efflux. Accordingly, the aim was to enhance dissolution rate and intestinal absorption of lopinavir. This employed co-processing with menthol which is believed to modify crystalline structures and inhibit intestinal efflux. Lopinavir was mixed with menthol at different molar ratios before ethanol assisted kneading. Formulations were evaluated using FTIR spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and dissolution studies. Optimum ratio was utilized to assess lopinavir intestinal permeability. This employed in situ rabbit intestinal perfusion technique. FTIR, DSC and XRD indicated formation of lopinavir-menthol co-crystals at optimum molar ratio of 1:2. Additional menthol underwent phase separation due to possible self-association. Co-crystallization significantly enhanced lopinavir dissolution rate compared with pure drug to increase the dissolution efficiency from 24.96% in case of unprocessed lopinavir to 91.43% in optimum formulation. Lopinavir showed incomplete absorption from duodenum and jejuno-iliac segments with lower absorptive clearance from jejuno-ileum reflecting P-gp efflux. Co-perfusion with menthol increased lopinavir intestinal permeability. The study introduced menthol as co-crystal co-former for enhanced dissolution and augmented intestinal absorption of lopinavir.