Novel pimozide-β-cyclodextrin-polyvinylpyrrolidone inclusion complexes for Tourette syndrome treatment

Abstract

Pimozide (PMZ), a first-line antipsychotic drug for the treatment of Tourette syndrome, suffers from reduced oral bioavailability problems due to its poor solubility. This study aimed at achieving higher solubility and consequently greater dissolution profile of the drug. Novel PMZ-β-cyclodextrin (β-CD) inclusion complexes in the absence and presence of polyvinylpyrrolidone (PVP-K30) were accomplished by kneading method. PMZ formed 1:1M stoichiometric binary and ternary inclusion complexes as indicated by the AL-type of phase solubility curves. An improvement in stability constant value (KS) of PMZ-β-CD complex in the presence of PVP-K30 conferred greater complexation efficiency. The results of FTIR and DSC studies revealed that the indoline ring of PMZ might be accommodated by the β-CD cavity upon complexation. PVP-K30 could establish superior electrostatic interactions and hydrogen bonding contacts in the molecular assembly of the ternary complexes. The incorporation of PVP-K30 also resulted in complete amorphization of the drug in complexes as referred by XRD and SEM studies. As a result, a greater solubility and significantly improved dissolution profiles were achieved when polymer and β-CD were present together in the system. Moreover, immediate release tablets containing ternary complexes [PMZ:β-CD (1:2M) with PVP-K30 (20%)] exhibited comparable physical properties and improved in vitro release profile relative to matrices incorporating pure PMZ. Thus, the ternary inclusion complexes and their formulations could represent promising therapeutic strategy for Tourette syndrome treatment.