Formulation and Optimization of Chitosan Microspheres for Nasal Delivery of Novel Calium Channel Blockers

Abstract

Nasal drug delivery is one of the promising routes for effective absorption of administered drugs. This route allows us to attain high bioavailability of the drug in question which otherwise would not have been possible through the conventional oral route. This is beneficial for drugs belonging the BCS class II such as Cilnidipine which have an inherently low aqueous solubility but have a high permeability. Utilizing the high permeability offered by nasal cavity for lipophilic drugs we aim to develop nasal mucoadhesive microspheres. Chitosan being a natural polymer is suitable for the safe and non-toxic administration of Cilnidipine. Crosslinking of the polymers allows us to obtain a sustained drug release, ideal for the gradual absorption of the drug. A major benefit of chitosan is its mucoadhesive property. This allows the retention of the administered microspheres onto the surface of the nasal mucosa providing retention of the drug delivery vehicle at the site of absorption. The formulation has been optimized by design of experiment and has allowed the elucidation of various input variables on the output variables. The effect of polymer concentration, inlet temperature and volume of crosslinking agent was studied on the output variables such as percentage yield, percentage drug entrapment efficiency and percentage drug release by 8th hour. The design of experiment using the Box-Behnken design allowed the study of the interacting factors to for the optimization of the formulation to develop a batch with high yield, high drug entrapment and lower drug release. To obtain the goals various methods were used for the synthesis of microspheres such as water-in-oil emulsion method. This method had a drawback of drug partitioning into the oil phase, to overcome this multiple emulsion method was utilized, however this increase the drug loading but not to desirable levels. Then using spray drying method delivered the best results.This method was studied in-depth and optimization with DoE was built upon it.