Donepezil Base: Physicochemical Characterization, HPLC Method Development, Validation and its Application for the Determination of Shelf Life in Developed Solid Lipid Nanoparticles

Abstract

Background/Objectives: Donepezil (DPL) is available as the hydrochloride salt (DPL-HCL) which is highly water-soluble, prompting leakage of the drug into water phase during solid lipid nanoparticles (SLNs) preparation which leads to reduce the entrapment efficiency as well as drug content. So, the drug was converted into its base form i.e. donepezil base (DPL base). The main objective of the work was to study the physicochemical characterization and identification of DPL base and to compare it with parent DPL-HCL, to develop a High-Performance Liquid Chromatography (HPLC) method for the detection of DPL base in SLNs. The develop method was used for the determination of shelf life of drug in SLNs. Methods: DPL-HCL was converted into DPL base simply by alkalization of DPL- HCL with NaOH and then extracted into dichloromethane (DCM) followed by drying to obtain DPL base. The HPLC method was developed and validated to quantify the DPL base for the determination of its shelf life in SLNs. The drug content in the developed SLNs was determined by extracting the DPL base using methanol as a solvent. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Results: DPL-HCL was successfully converted into DPL base with a yield value of 88.61%. The optimized mobile phase was comprised of 0.02 M phosphate buffer (pH 7.4), methanol and Acetonitrile (ACN) (40:50:10 v/v/v). The pH of mobile phase was adjusted with o-phosphoric acid. The linearity range of the developed method was found to be 0.5-80 µg/mL with LOD and LOQ value 0.086 and 0.263 µg/ml respectively. The shelf life of the DPL base in SLNs was found to be 2.29 years. Conclusion: The HPLC method for donepezil base was successfully developed and validated. RSD values for validated parameters were < 2, indicating the authenticity of the developed method. The method was successfully used for the determination of shelf life of the drug in SLNs.