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Context: Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly., Objective: The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient., Methods and Materials: The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®., Results and Discussion: Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug., Conclusion: The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

The effect of deprotenizing agents on recovery of donepezil hydrochloride in the development of a simple, rapid, selective and sensitive high performance liquid chromatography method for quantification of donepezil hydrochloride in human plasma was described. The deprotenizing agents were comprised of, perchloric acid, methanol, acetonitrile, chloroform and their mixtures. The chromatographic separation was carried out using reversed phase C18 column (Agilent Eclipse Plus C18) with UV detection at 268 nm. The mobile phase was comprised of 0.01 M potassium dihydrogen phosphate buffer, methanol and acetronitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%). A combination of perchloric acid and methanol gave a cleaner sample with a good recovery of donepezil hydrochloride of above 96%. The method showed intraday precision and accuracy in the range of 6.82% to 1.5% and 3.13% to 1.12% respectively, while interday precision and accuracy ranged between 1.06% to 4.71% and 13.01% to 6.43% respectively. The standard calibration curve was linear from 30ng/mL to 4000ng/mL, with a correlation coefficient of 0.9965±0.0034. The retention time of donepezil was 5.9 min with a run time of 7.0 min. The method can be applied to analyze large batch plasma samples in pharmacokinetic studies.

Context: Difficulty in swallowing tablets or capsules has been identified as one of the contributing factors to non-compliance of geriatric patients. Although orally disintegrating tablet was designed for fast disintegration in mouth, the fear of taking solid tablets and the risk of choking for certain patient populations still exist., Objective: The objective of this study was to develop and characterize orally disintegrating film (ODF), which was prepared using different combinations of polymers, plasticizers and fillers., Materials and Methods: Effects of hydroxypropyl methylcellulose (HPMC), polyethylene glycol 400 (PEG 400), glycerin, polyvinyl pyrrolidone (PVP), mannitol and microcrystalline cellulose (MCC) on physical property of ODF formed were studied. The ODF was prepared using the solvent casting method., Results: Increase in HPMC concentration formed ODF with greater tensile strength. Incorporation of plasticizer (PEG 400 and glycerin) reduced tensile strength but increased elasticity of the ODF formed. PVP increased both tensile strength and elasticity of the ODF. Increase in MCC:mannitol ratio reduced the tensile strength and elasticity of the ODF. Disintegration time of film decreased corresponding to decrease in tensile strength of the film. Formulation R with the optimum tensile strength (13.10 N/mm(2)), bending flexibility (40 times) and disintegration time (41.50 s) was chosen as final formulation. A total of 80% of the drug was released within five minutes and the ODF was stable at least for one year actual condition., Conclusion: An ODF containing donepezil HCl was developed and characterized. The donepezil HCl ODF has the potential to improve the compliance of Alzheimer disease patients.

An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.

The aim of this study was to develop a taste-masked oral disintegrating film (ODF) containing donepezil, with fast disintegration time and suitable mechanical strength, for the treatment of Alzheimer's disease. Hydroxypropyl methylcellulose, corn starch, polyethylene glycol, lactose monohydrate and crosspovidone served as the hydrophilic polymeric bases of the ODF. The uniformity, in vitro disintegration time, drug release and the folding endurance of the ODF were examined. The in vitro results showed that 80% of donepezil hydrochloride was released within 5 minutes with mean disintegration time of 44 seconds. The result of the film flexibility test showed that the number of folding time to crack the film was 40 times, an indication of sufficient mechanical property for patient use. A single-dose, fasting, four-period, eight-treatment, double-blind study involving 16 healthy adult volunteers was performed to evaluate the in situ disintegration time and palatability of ODF. Five parameters, namely taste, aftertaste, mouthfeel, ease of handling and acceptance were evaluated. The mean in situ disintegration time of ODF was 49 seconds. ODF containing 7 mg of sucralose were more superior than saccharin and aspartame in terms of taste, aftertaste, mouthfeel and acceptance. Furthermore, the ODF was stable for at least 6 months when stored at 40°C and 75% relative humidity.