Preparation and Evaluation of Taste-Masked Donepezil Hydrochloride Orally Disintegrating Tablets

다국어 초록 (Multilingual Abstract)

<P>The purpose of this research was to prepare and evaluate a non-bitter donepezil hydrochloride (DH) orally disintegrating tablet (ODT) for enhanced patient compliance. Taste masking was done by preparing microspheres with different ratios of drug and Eudragit<SUP>®</SUP> EPO using spray drying method. The entrapment of the drug into microspheres was confirmed by scanning electron microscope (SEM) and X-ray powder diffraction. It was found that microspheres with a drug–polymer ratio of 1 : 2 could mask the taste obviously by inhibiting the release of DH in simulated salivary fluid. Microspheres-loaded tablets containing Polyplasdone NF and Low substituted Hydroxypropyl Cellulose (L-HPC) both at a 10% level showed rapid disintegration, <I>in vitro</I> (15.5 s) and <I>in vivo</I> (19.8 s), which were faster than that of marketed tablets (36.7, 41.3 s, respectively). Results from taste evaluation in human volunteers revealed that the ODTs with taste-masked microspheres had significantly enhanced palatability. Dissolution <I>in vitro</I> and pharmacokinetics in rats were evaluated for the tested ODTs compared to the donepezil hydrochloride commercial product (ARICEPT<SUP>®</SUP>). Both tablets showed comparable dissolution patterns <I>in vitro</I> and similar area under curve from 0 to 24 h (<I>AUC</I><SUB>0—24</SUB>), <I>C</I><SUB>max</SUB> and <I>T</I><SUB>max</SUB> of DH <I>in vivo</I> to each other, suggesting that the tested ODTs might give the similar drug efficacy in rats compared to that of ARICEPT<SUP>®</SUP>. Thus, it was concluded that DH ODTs with masked taste were obtained by Eudragit<SUP>®</SUP> EPO-based microspheres, drug loaded microspheres neither decreased the bioavailability nor delayed the release of DH.</P>