Chitosan/pectin polyelectrolyte complexes for nasal delivery of antipsychotic drugs.

Novel formulations and new routes of administration for psychotropic drugs can offer advantages over older formulations in terms of effcacy, tolerability and compliance. Short-acting and long-acting preparations are useful alternatives to the traditional formulations, which can provide more acceptable forms of medication for patients [1]. Recently nasal mucoadhesive systems have been investigated with the aim of altering the pharmacokinetics of orally and par- enterally administered drugs in a fashion that can enhance their pharmacologic profiles [2]. Infact, the large surface area, porous endothelial basement mem- brane, high total blood ow of the nasal mucosa ensure a rapid absorption of compounds under circumvention of the hepatic first-pass metabolism. Moreover, the accessibility of the nasal route provides a quick and easy self-medication when compared to other routes, thus improving patient compliance. A major problem of nasal drug delivery is the mucociliary clearance mechanism that rapidly removes non-mucoadhesive applied dosage forms from the absorption site. Mucoadhesive polymers can be used to prevent the rapid clearance of the drug formulation increasing the nasal residence time and thereby allowing longer absorption times. The purpose of this study was the preparation and character- ization of mucoadhesive nasal inserts based on chitosan/pectin polyelectrolyte complexes [3, 4] for antipsychotic drug delivery. A suspension of chitosan/pectin complexes with or without the model drug (chlorpromazine hydrochloride) was lyophilized into small inserts. Complexation yield, FT-IR spectra and TGA thermograms were analysed to study the degree of interactive strength between polyions. Morphological characteristics, in-vitro swelling, mucoadhe- sion, release and permeation tests were performed in order to investigate insert ability to deliver antipsychotic agents in the nasal cavity. The results showed that higher amount of pectin in the complexes provides greater water uptake particularly at alkaline pH due to the very low degree of interaction between the two polymers and the great amount of free negative charges. Moreover, poly- electrolyte complexes containing high percentages of pectin showed the best in vitro mucoadhesion capacity due to their great swelling ability. Finally, the presence of increasing amounts of pectin allowed the interaction with chlorpro- mazine inducing the formation of less rehydratable inserts thus limiting drug release. This investigation verified the formation of polyelectrolyte complexes between chitosan and pectin at pH values in the vicinity of the pKa interval of the two polymers and confirmed the potential of these complexes, capable of achieving antipsychotic drug delivery in the nasal cavity. [1] S. Keith, 2006. Prog. Neuropsychopharmacol. Biol. Psychiatry 30, 996- 1008. [2] L. Illum, 2003. J. Control. Release 87, 187-198. [3] F. Bigucci et al., 2008. Eur. J. Pharm. Sci. 35(5), 435-441. [4] B. Luppi et al., 2009. J. Pharm. Pharmacol. 61(2), 151-157