Studies On The Compressibility And Stability Of Aspirin And Ranitidine Hydrochloride Coating Particles

Combination preparation plays an important role in clinical treatment because of its better and wider curative synergism and weaker side effects. However, the existence of incompatibility between active ingredients or between active ingredients and excipients presents a serious obstacle in the preparation of such combination solid dosage forms. Aspirin is often used as a combination constituent in combination preparations. Because of its hydrolysis property and the existence of the acetyl group with high reactivity in its structure, aspirin is easy to produce incompatibility with other drugs. Furthermore, the content of aspirin in combination preparation is usually high and the drug content uniformity is also a considerable problem. Ranitidine hydrochloride, a water-soluble drug, is easy absorb moisture and produce discoloration. Moreover, there exists incompatibility between aspirin and ranitidine hydrochloride. In this study, aspirin and ranitidine hydrochloride were selected as the model drugs. With a new reformed bottom spray fluidized bed, the model drugs were coated respectively and the different coating methods were studied. A matrix tablet was prepared basing on the difference of compressibility between the coating particles of the two drugs, which would be a new way to overcome the incompatibility in combination tablets.The basic properties and stabilities of the two model drugs were investigated. It was clarified that the two drugs were of bad flowability judged from the Carr's index evaluation results. Aspirin was sensitive to the humidity and pH whereas ranitidine hydrochloride was instable to the humidity and the light. Therefore, the effects of some excipients on the stability of the model drugs were also investigated. The excipients selected could not affect the stability of aspirin in pH while except lactose, starch and microcrystalline cellulose were disadvantageous to ranitidine hydrochloride stability because of their moisture-absorption characteristics. Furthermore, the interactionbetween aspirin and ranitidine hydrochloride was determined using the DSC method.Aspirin was granulated and coated without adding any diluents with the HPMC water solution as a binder. With other operation conditions fixed, the effects of fluidizing air flow volume and atomizing air flow volume on the product particles properties were investigated. It was found that the fluidizing air flow volume mainly affected the yield and particle size whereas it had no significant effects on the appearances, strength and compressibilities of product particles in comparison with the atomizing air flow volume. Basing on these analysis, the powder supplied(F), binder concentration(C), binder supplied(Ws) and spray rate(v) were selected as the controlling factors and the yield(Y), average particle diameter(d5o), the angle of repose( 0 ) and the degradation of aspirin(D) were the response variables. The further optimization of the detailed operation conditions was carried out using Artificial Neural Network(ANN). The relationships between controlling factors and response variables were analyzed through plotting three-dimensional diagrams and contour figures and the optimum area was determined using the superimposed two-dimensional diagrams. From this optimum area, one of the optimum operation conditions was selected and with this condition, aspirin granules had high yield, suitable particle diameter, good flowability and low degradation. Furthermore, from the tensile strength of the tablets compressed with the optimum granules, it could be concluded that the optimized aspirin granules had a good compressibility.Due to the extreme solubility in the water, the original ranitidine hydrochloride powder was coated using Eudragit El 00 organic solvent system (EtOH:water=97:3). There existed a great number of fine particles in original powder, only if the coating weight gained got to 20%, there was an obvious decrease of fine powder in the particle distribution. Therefore, the coating was carried out after preliminary gra...