Preparation and In Vitro/Ex Vivo Evaluation of Buccoadhesive Discs of an Anti-Parkinson Drug: Relationship between Mucoadhesivity, Drug Release and Permeability

Abstract

IntroductionSelegiline hydrochloride (Sel) is a drug utilized for the therapy of early-stage Parkinson's disease, depression, and dementia. In usual clinical doses, it is an elective invariable MAO-B inhibitor. Nasal and subcutaneous routes exert some limitations such as lower retention time for nasal solution and difficulty in self-administration for injectable ones. These forms have certain disadvantages. Film and disc of buccomucoadhesive drugs are of delivery profit, as the film solves and the oral drug is administered through absorption in the mouth (buccally or sublingually) and/or in small gut (intestinally). 1Hence the aims of present project were; to extend a novel drug delivery system for Sel which might be carried via the buccal route (discs created with microspheres), to exclusively target the mucous area in order to attain a quick relief by rapid beginning of operation; to enhance bioavailability; and to elude the secondary dose administration. The buccal discs can be better alternates that may decrease the side effects related to oral and parenteral remedies. In treating the Parkinson's, constant levels of the drug are required in the blood for an extended period. This can be settled by designing a buccal drug delivery system that could deliver the drug via oral buccal mucosa. The hydrophilic Sel may show low bioavailability when administered through the buccal route. And once in the systemic circulation, hydrophilicity is required for effective distribution. Therefore, the use of buccoadhesive Sel was proposed. However, in order to achieve the result, the modification of its absorption was A B S T R A C TBackground: Selegiline hydrochloride (Sel) is a drug applied for the therapy of early-step Parkinson's disease. In usual clinical doses, it is an elective irreversible MAO-B inhibitor. This study intended to formulate mucoadhesive microspheres of selegiline with the objective of improving the therapeutic efficacy, patient compliance and bioavailability. Methods: The microspheres were prepared by emulsion solvent evaporation method (O1/ O2) using hydroxypropyl methylcellulose (HPMC). In the current study, bucco-adhesive microspheres were prepared with different drug to polymer ratios and characterized by encapsulation efficiency, particle size, Differential Scanning Calorimetry (DSC), FTIR Fourier Transform Infrared Spectroscopy (FTIR), flowability, the degree of swelling and surface pH, mucoadhesive character, retentive time, and drug release studies. Results:The best drug to polymer ratio in microspheres was 1:2 (as F1). The production yield microspheres F1 showed production yield of 84.79%, mean particle size of 744.73 μm and loading efficiency of 53.33%. The DSC exhibited the property of selegiline loaded microspheres changed to amorphous form. The FTIR spectrum proposed that the drug kept its chemical stability during the emulsification process. The results showed that the microspheres of F1 had faster release than the microspheres of F2 (1:4), F3 (1:6), and commercial tablet (p<0.05). The mic...