Optimized Taste-Masked Microparticles for Orally Disintegrating Tablets as a Promising Dosage Form for Alzheimer's Disease Patients.

Lalinthip Sutthapitaksakul,Crispin R Dass,Kasitpong Thanawuth,Pornsak Sriamornsak

doi:10.3390/pharmaceutics13071046

Abstract

The objective of this research was to optimize the tasted-masked microparticles for orally disintegrating tablets containing donepezil hydrochloride using quality risk assessment and design of experiment approaches. The double emulsion solvent evaporation technique using aminoalkyl methacrylate copolymer (AMC) was used to prepare taste-masked microparticles. Factors affecting the quality of the taste-masked microparticles were analyzed using an Ishikawa diagram. A risk-ranking approach was used to rank the formulation and process risks. Furthermore, the effect of AMC quantity, stirring time, and volume of outer water phase on various responses, such as particle size, the amount of drug dissolved at 5 min (Q5) in simulated saliva fluid, and mean dissolution time (MDT) in simulated gastric fluid, was investigated using the Box-Behnken design. The optimized microparticles were then used to prepare orally disintegrating tablets (ODTs) and evaluated by in vitro and in vivo testing. The results demonstrated that particle size was influenced by the AMC amount and stirring time. Q5 was significantly affected by the amount of AMC and the volume of the outer water phase. On the other hand, these two factors had a positive effect on MDT. The optimized microparticles had a particle size of 174.45 ± 18.19 µm, Q5 of 5.04%, and MDT of 5.97 min. The ODTs with taste-masked microparticles showed acceptable in vitro dissolution with an MDT of 5 min. According to the results of a panel of six human volunteers, they greatly improved palatability.

Highlights

In recent years, the global demographic structure has shifted from younger to older populations, with the proportion of people aged above 65 expected to rise from 703 million to 1.5 billion by 2050 [1]
Throughout the theexperiment, experiment, the thematerial materialused, used,ultrasonicator ultrasonicatoremployed employedin inthe thefirst first emulsification, emulsification, stirrer stirrer used used in inthe thesecond secondemulsification, emulsification,solvent solventevaporation evaporation condition, condition, and were all all kept constant, while temperature and relative humidity were andproduction productionscale scale were kept constant, while temperature and relative humidity monitored
The results demonstrated root mean square error (RMSE) of particle size, Q5, and mean dissolution time (MDT) of 11.63, 0.50, and 1.06, respectively, 3.2.4

Summary

Introduction

The global demographic structure has shifted from younger to older populations, with the proportion of people aged above 65 expected to rise from 703 million to 1.5 billion by 2050 [1]. Among several age-associated health issues, the prevalence of neurodegenerative diseases, such as Alzheimer’s and other types of dementia, is exceptionally high in this population. Alzheimer’s disease affects about 10% of people aged above 65 and 50% of people aged above 85 years, with the number expected to reach 131 million by 2050 [2]. The commercial DPH products for oral administration, such as conventional tablets and capsules, may not be suitable for these individuals [6]. The development of DPH orally disintegrating tablets (ODTs) may be a good option because they are designed to rapidly disintegrate into small

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Conclusion