Abstract. 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.

This study examined the mechanical (hardness, compressibility, adhesiveness, and cohesiveness) and rheological (zero-rate viscosity and thixotropy) properties of polyethylene glycol (PEG) gels that contain different ratios of Carbopol 934P (CP) and polyvinylpyrrolidone K90 (PVP). Mechanical properties were examined using a texture analyzer (TA-XT2), and rheological properties were examined using a rheometer (Rheomat 115A). In addition, lidocaine release from gels was evaluated using a release apparatus simulating the buccal condition. The results indicated that an increase in CP concentration significantly increased gel compressibility, hardness, and adhesiveness, factors that affect ease of gel removal from container, ease of gel application onto mucosal membrane, and gel bioadhesion. However, CP concentration was negatively correlated with gel cohesiveness, a factor representing structural reformation. In contrast, PVP concentration was negatively correlated with gel hardness and compressibility, but positively correlated with gel cohesiveness. All PEG gels exhibited pseudoplastic flow with thixotropy, indicating a general loss of consistency with increased shearing stress. Drug release T50% was affected by the flow rate of the simulated saliva solution. A reduction in the flow rate caused a slower drug release and hence a higher T50% value. In addition, drug release was significantly reduced as the concentrations of CP and PVP increased because of the increase in zero-rate viscosity of the gels. Response surfaces and contour plots of the dependent variables further substantiated that various combinations of CP and PVP in the PEG gels offered a wide range of mechanical, rheological, and drug-release characteristics. A combination of CP and PVP with complementary physical properties resulted in a prolonged buccal drug delivery.

An ODF containing donepezil HCl was developed and characterized. The donepezil HCl ODF has the potential to improve the compliance of Alzheimer disease patients.

The purpose of this study is to evaluate amphiphilic block copolymers, a new class of additives, for the habit modification of pharmaceuticals. The additive chosen is poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA). The model compound chosen is tolazamide, an oral hypoglycemic pharmaceutical agent. Crystallization was carried out in aqueous media by pH adjustment, with or without additives. PEG-b-PLA was found to be very effective in modifying the crystal habit of tolazamide. The habit changed from a needle shape to a plate shape at a concentration of 12.5 μg/mL. This change in habit required both blocks and could not be achieved in the presence of either block alone. A small amount of copolymer (0.55% weight) was found on/in tolazamide particles crystallized in the presence of 30 μg/mL of copolymer. Washing the crystals with toluene effectively removed the copolymer. It is thus concluded that the block copolymer is mainly adsorbed on the crystal surface(s) rather than being incorporated into the lattice of tolazamide crystals. The recrystallized tolazamide is of the same crystal form as that of the original solid, regardless of the concentration of the copolymer used.