Published Paper Details:

In the present work, mucoadhesive nasal microspheres containing clozapine were formulated and evaluated for increasing its bioavailability in cerebrospinal fluid. Clozapine is an antipsychotic agent that is of BCS class II, hence needs to improve its bioavailability at the central nervous system CNS). To make the drug delivery system safer, natural ingredients were used. Various natural polymers and cross-linkers were screened. Starch is a natural polymer crosslinked with citric acid as natural crosslinker. Clozapine-loaded cross-linked starch microspheres (CSMs) were successfully developed for intranasal delivery for CNS targeting using single emulsion cross-linking method. Ex-vivo mucoadhesion study and In-vivo brain targeted study have been carried out using prepared CSMs. More than 90% mucoadhesive strength was achieved using starch as a natural polymer. Noncompartmental analysis was carried out to calculate the pharmacokinetic parameters. Clozapine concentration was analyzed in both plasma and CSF using HPLC analysis. There was a 1.5-fold increase in the bioavailability of clozapine when administered intranasally. Drug targeting efficiency (DTE %) and Drug targeting potential (DTP %) were calculated. There was a 2.4-fold increase in % DTE and a 2.04-fold increase in % DTP for CSMs as compared to clozapine. In-vivo studies showed increased relative bioavailability with the nasal route as compared to the oral route. The intranasal route has helped to attain significant therapeutic levels of the antipsychotic drug in the Cerebrospinal fluid by surpassing the blood-brain barrier and hepatic first-pass effect.