Design and Optimization of Sustained-Release Trihexyphenidyl Hydrochloride Nanoparticles: Design of the Experiment Approach

Background: Trihexyphenidyl chloride (THP) is an antidyskinetic medication used in single and combination therapy to symptomatically treat Parkinson's disease. Due to its fast metabolism and short elimination of half-life, it causes changes in plasma concentrations and requires frequent dosage. Objective: The aim of this study was to prepare a sustained release formulation of Trihexyphenidyl chloride (THP). Materials and Methods: Using chitosan as the natural polymer, the polymeric nanoparticles were prepared by using the ionic gelation method. A 3² response surface methodology was used to optimize the effects of independent variables, such as the amount of polymer (X1mg) and the amount of copolymer (X2mg), on dependent variables, such as entrapment efficiency (% EE) (Y1) and drug release (% DR) (Y2). Results: The prepared formulations were evaluated for Fourier transform-infrared (FTIR), X-ray Diffraction, Field scanning micrographs (FESEM), and In vitro drug release. Higher drug entrapment efficiency was observed for batch T11. FTIR confirmed the loading of trihexyphenidyl drug into the chitosan matrix. X-ray diffraction pattern indicated that the degree of crystallinity of pure drug was reduced in the formulated NPs. Conclusion: The drug release from the formulated batches (T1-T13) showed sustained-release action for around 9-14 hrs. The technique reduced the dosing frequencies and possible side effects of trihexyphenidyl chloride.