Research On Preparation Technology Of Fluoxetine Hydrochloride Orally Disintegrating Tablets

Fluoxetine hydrochloride(Flu) is a selective serotonin reuptake inhibitor which is clinically effective for the treatment of depression. It was developed by Eli Lilly, approved by FDA and marketed in the USA in 1987.At present, the main dosage forms for Flu are oral preparations, of which Prozac is the most widely used. Due to its very bitter and unpleasant taste, there is still no approved and marketed product of Flu orally disintegrating tablets (Flu ODTs). This study aimed to develop an efficient taste masking technology for Flu, to screen the formulation and preparation process of Flu ODTs, and to establish the quality standard of Flu ODTs The main results are as follows:(l)Taste masking of Flu:Several methods were employed to mask the taste of Flu, such as use of sweeteners and flavoring agents, inclusion of drug with p-cyclo dextrin, complexation of drug with ion-exchange resins, solid dispersion and precipitation. The results of taste-masking effect and drug dissolution showed that the method of precipitation with the use of acrylate copolymer was feasible and efficient. The composition was optimized using single factor experimental design:the weight ratio of Flu: acrylate copolymer was 1:1 and the amount of precipitation-aid agent was set at 2%.The taste-masked power was characterized by SEM> XRD and FTIR, The spectra showed that the crystallinity of Flu was decreased after taste-masking treatment, there might be interaction between Flu and acrylate copolymer.(2) Formulation and preparation of Flu ODTs:Flu ODTs was prepared by the method of wet granulation and tableting. The formulation of Flu ODTs was screened and optimized as follows:tablet weight of 400mg, binder of 1% PVPk-30 aqueous solution including 3% SDS, disintegrant of 5% L-HPC and 10% PVPP. The dissolution result showed that the self-made Flu ODTs was able to disintegrate in the buccal cavity in less than 60s, the dissolution was fast and complete in 0.1mol/L HCl(90% in 15min)(3) Stability of Flu ODTs:The results of stress test and accelerated test showed that the appearance of the product, content, dissolution and related substances did not change significantly during the whole testing period, indicating that the self-made Flu ODTs were of good stability.(4) Analysis method and Quality control of Flu ODTs:The HPLC analysis method for determination of the content and related substances and UV spectrophotometry for dissolution testing of Flu ODTs were established, the results showed that the analysis methods were specific, accurate and sensitive. Quality standards of Flu ODTs was also established in this paper.