Chitosan based pentazocine microspheres for intranasal systemic delivery: development and biopharmaceutical evaluation

Bioadhesive chitosan microspheres (Ms) of pentazocine (Pz) for intranasal s ystemic delivery were prepared with the aim of avoiding the first pass effe ct, and thus improving the bioavailability and achieving sustained and cont rolled blood level profiles, as an alternative therapy to injection and to obtain improved therapeutic efficacy in the treatment of chronic pain such as cancer, trauma and post-operative pain, etc. The formulation variables w ere drug loading, polymer concentration, stirring rate during crosslinking and oils. The microspheres (Ms) were subjected to evaluation for. physical characteristics, such as particle size, incorporation efficiency, swelling ability, in vitro bioadhesion, in vitro drug release characteristics and in vivo performance in rabbits. Application of in vitro data to various kinet ic equations indicated matrix diffusion controlled drug delivery from chito san Ms. Drug loading, polymer concentration and stirring speed influenced t he drug release profiles significantly while oils had negligible effect. II I vivo studies indicated significantly improved bioavailability of Pz from Ms with sustained and controlled blood level profiles as compared to i.v., oral and nasal administration of drug solution. Good correlation was observ ed between in vitro and in vivo data.