An industrial procedure for the intestinal permeability enhancement of acyclovir: in-vitro and histological evidence.

Acyclovir, an antiviral drug, has low bioavailability due to its low permeability. Consequently, high drug doses and frequent administration are required. This study investigates the use of span 60, at different concentrations, as a granulating agent to enhance drug permeability using an industrial procedure on a pilot scale. The micromeritics, drug content, drug crystallinity, drug partition coefficient, and drug release of the produced formulations were examined. The findings revealed an enhanced drug partition coefficient, suggesting drug entrapment in the polar portion of span 60. The drug release profiles exhibited rapid and complete drug release. The improvement of the drug permeability was evaluated using a modified non-everted sac technique. Notably, drug permeability through the rabbit intestine significantly improved, as evidenced by various calculated permeation parameters, providing insights into the drug absorption mechanism. The widening of the paracellular pathway was observed through histological examination of the rabbit intestinal segment, which aligns with the drug absorption mechanism. The utilization of a paracellular pathway enhancer as a granulating agent holds promise as a strategy to enhance the oral bioavailability of class III drugs. Overall, this study presents a novel drug delivery approach to enhance drug permeation and bioavailability, with potential implications for other medications.

Formulation of acyclovir-loaded solid lipid nanoparticles: design, optimization, and in-vitro characterization.

The goal of this study was to design, optimize, and characterize Acyclovir-loaded solid lipid nanoparticles (ACV-SLNs) concerning particle size, zeta potential, entrapment efficiency, and release profile. Full factorial design (23) was applied and the independent variables were surfactant type (Tween 80 and Pluronic F68), lipid type (Stearic acid and Compritol 888 ATO), and co-surfactant type (Lecithin and Sodium deoxycholate). The microemulsion technique was used followed by ultrasonication. The ACV-SLNs had a particle size range of about 172-542 nm. The polydispersity index (PDI) was found to be between 0.193 and 0.526. Zeta potential was in the range of -25.7 to -41.6 mV indicating good physical stability. Entrapment efficiency values were in the range of 56.3-80.7%. The drug release kinetics of the prepared formulations was best fitted to Higuchi diffusion model. After storing ACV-SLNs at refrigerated condition (5 ± 3 °C) and room temperature (25 ± 2 °C) for 4 weeks; we studied the change in the particle size, PDI, and zeta potential. The selected optimized formulation (F4) was containing Compritol, Pluronic F68, and Lecithin. These results indicated the successful application of this design to optimize the ACV-SLNs as a promising delivery system.

Formulation of acyclovir-loaded solid lipid nanoparticles: 2. Brain targeting and pharmacokinetic study.

Acyclovir (ACV) is widely used in the treatment of herpes encephalitis. The present study was conducted to prepare chitosan-tween 80 coated solid lipid nanoparticles (SLNs) as a delivery system for brain targeting of ACV in rabbits. The SLNs were prepared and coated in one step by microemulsion method using a coating solution containing chitosan (0.1% w/v) and tween 80 (2% w/v) for loading sustained release ACV. In vitro characterization was performed for coated ACV-SLNs. Concerning in vivo experiments; a single intravenous bolus dose of coated ACV-SLNs was given versus free ACV solution to rabbits (62 mg/kg). Plasma pharmacokinetic parameters were calculated from the ACV concentration-time profiles in plasma using the two compartmental analysis. The values of AUC0-∞ and MRT of coated ACV-SLNs were higher than free drug by about twofold, 233.36 ± 41.56 µg.h/mL and 1.81 ± 0.36 h, respectively. The noncompartmental analysis was conducted to estimate the brain pharmacokinetic parameters. The AUC0-∞ brain/AUC0-∞ plasma ratio for coated ACV-SLNs and free ACV was 0.22 and 0.12, respectively. These results indicated the effectiveness of using coated ACV-SLNs for brain targeting.