Spray-Dried Buccal Mucoadhesive Microparticles of Venlafaxine Based on Cress Seed Mucilage: In Vitro, in Vivo Evaluation in Rabbits

摘要

Lepidium sativum Linn. (Cruciferea) is known as garden cress or cress. Venlafaxine is prescribed in schizophrenia and anxiety. It shows a tendency of hepatic first-pass metabolism, which affects its bioavailability. The objective of this study is the extraction of cress seed mucilage and development of buccal mucoadhesive microparticles of venlafaxine based on the mucilage using a spray-drying technique. The optimized formulation was evaluated in vitro and the bioavailability of the same formulation in rabbits was assessed. Cress seed mucilage was extracted and used to prepare microparticles with varying concentrations in formulations F1-F5 (1-5% w/w) using a spray-drying technique. The microparticles were evaluated for yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, and in vitro drug release. Microparticles were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction studies. In vivo evaluation was carried out in rabbits. Formulation FS showed maximum mucoadhesion (88.38 ±1.46%), greater incorporation efficiency (89.42 ± 2.52%), and the highest swelling index (0.93 ±0.01) compared to the other formulations. F5 showed a marked increase in bioavailability after buccal administration (52.55%) compared to an oral route (39.40%). Time to reach C_(max) of 23.49 ± 0.33 ng/mL was 120 min for buccal microparticles in comparison to oral solution, which took 180 min to reach C_(max) of 17.98 ±1.14 ng/mL. Cress seed mucilage is suitable for production of the mucoadhesive microparticles using a spray-drying method because significant improvement in bioavailability by buccal mucoadhesive microparticles was observed.