Preparation and Evaluation of Valacyclovir Hydrochloride Ocular Inserts by Hot Melt Extrusion Technique

摘要

The objective of the current study was to investigate the processability of Hot Melt Extrusion to formulate Ocular Inserts of Valacyclovir Hydrochloride and Evaluate its drug release in vitro and in vivo. Valacyclovir is the prodrug of Acyclovir, which is used in treatment of ocular keratitis and HSV infections. The bioavailability of the prodrug is better than the acyclovir and it is proved to permeate extensively through the corneal barrier. The polymer of choice was KlucelRTM Pharm MF and JF grades for the study. To optimize the formulation, different physical mixtures of the polymers and plasticizers (PEG 400 and Propylene glycol) were prepared. The physical mixture was extruded through co -- rotating twin-screw Haake MiniLab ThermoFisher RTM Scientific extruder. The obtained ocular inserts were cut into dimensions of 4mmx2mmx1mm to have suitable product instillation in the eye. Ocular inserts were evaluated for drug content, weight variation, uniformity of thickness and in vitro and in vivo drug release. The thermal characterization of ocular inserts was observed using Differential Scanning Calorimetry (DSC). Morphology of the ocular inserts was observed using Scanning Electron Microscopy (SEM). The polymer interactions or incompatibilities was assessed using FTIR. Klucel RTM Pharm MF exhibited desired results than Klucel RTM Pharm JF and was easy to extrude to prepare ocular inserts. The ocular inserts were able to provide sustained drug release compared to eyedrop solution and then dissolve completely in 9 hours.