Preparation and In Vitro Characterization of Mucoadhesive Polyvinyl Alcohol Microspheres Containing Amlodipine Besylate for Nasal Administration

Abstract:

Amlodipine Besylate microspheres for intranasal administration were prepared with an aim to avoid first-pass metabolism, to achieve controlled blood level profiles and to improve therapeutic efficacy. Polyvinyl Alcohol, a water soluble synthetic polymer, was used in the preparation of microspheres by employing phase separation emulsification technique. The formulation variables were drug concentration, emulsifier concentration, temperature, agitation speed and polymer concentration. All the formulations were evaluated for particle size, particle shape and surface morphology by Scanning Electron Microscopy, percentage yield, drug entrapment efficiency, in vitro mucoadhesion test, degree of swelling and in vitro drug diffusion through sheep nasal mucosa. The microspheres obtained were free flowing, spherical and had a mean particle size of 10.2 ± 3.08 μm to 37.2 ± 1.52 μm very much suitable for nasal delivery. Increasing the polymer concentration resulted in increased drug entrapment efficiency and increased particle size. Amlodipine Besylate was entrapped into the microspheres with an efficiency of 64.5 ± 2.08 % to 83.6 ± 1.05 %. The prepared microspheres revealed good mucoadhesion properties, swellability and sustained the release of the drug over a period of 8 h. The data obtained were analysed by fitment into various kinetic models; it was observed that the drug release was matrix diffusion controlled and the release mechanism was found to be non-Fickian. Stability studies were carried out on select formulations at 5⁰C ± 3⁰C, 25⁰C ± 2⁰C / 60% RH ± 5% RH and 40⁰C ± 20C / 75% RH ± 5% RH for 90 days. The drug content was observed to be within permissible limits and there were no significant deviations in the in vitro mucoadhesion and in vitro drug diffusion characteristics.

Keywords: Mucoadhesive microspheres, Amlodipine Besylate, Phase separation emulsification technique, Drug entrapment efficiency, Degree of swelling, In vitro mucoadhesion studies, Nasal drug delivery