Optimization of donepezil hydrochloride-loaded microparticles produced by double emulsion technique

Abstract

Donepezil hydrochloride (DPH) is a bitter indanone and piperidine derivative that acts as a reversible cholinesterase inhibitor and has been approved for use in all stages of Alzheimer’s disease. Patients with Alzheimer’s disease may experience swallowing difficulties as the disease progresses. Orally disintegrating tablets (ODTs) with DPH have been created to make drug administration easier. As ODTs are designed to disintegrate quickly in the mouth, they may come into contact with taste receptors, resulting in a bitter taste. As a result, the objectives of this study were to mask the bitter taste of DPH and create ODTs with taste-masked microparticles. Microencapsulation by double emulsion solvent evaporation technique using aminoalkyl methacrylate copolymer (AMC) as an encapsulation polymer was used to prepare taste-masked DPH-loaded microparticles. A Box-Behnken design was employed to investigate the effect of AMC amount, stirring time, and volume of outer water phase on particle size, in vitro drug dissolution at 5 min (Q5) in simulated saliva fluid, and mean dissolution time (MDT) in simulated gastric fluid. The results demonstrated that AMC amount and stirring time had a significant influence on particle size. While Q5 and MDT was influenced by AMC amount and volume of external water phase. After validation of the developed model, the optimization was carried out. AMC amount of 5.7 g, stirring time of 148 s, and volume of external phase of 350 mL were the optimum condition to prepare microparticles with desired properties. The optimized product was further characterized and incorporated in ODTs, which prepared by the direct compression method. The effect of super-disintegrants, i.e., sodium starch glycolate, croscarmellose sodium, and crospovidone, on wetting time and in vitro disintegration time were studied. The ODT containing 4% crospovidone was chosen for in vivo evaluation as it provided short wetting time and rapid in vitro disintegration. The in vivo results showed that the taste-masked microparticles-loaded ODTs with acceptable palatability were successfully prepared. From the results, it can be concluded that the taste-masked microparticles were successfully prepared by double emulsion solvent evaporation technique. The effect of independent factors and optimization can be determined by implementing Box-Behnken design. Lastly, the ODTs containing taste-masked microparticles with acceptable properties were successfully prepared.

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