Application of reverse engineering in the development of caffeine tablets / 国际药学研究杂志

ABSTRACT

Objective: The reverse engineering technology was used to analyze the prescription and process of Good Sense Stay Awake®, the reference listed drug of caffeine tablets, in order to provide guidance for the development of generic caffeine tablets. Methods: Firstly, the prescription information of the reference listed drug was obtained by literature research. Then, quantitative analysis of the composition of the prescription was achieved by the high-performance liquid chromatography with a crystal refractive index detection and the gravimetric analysis method;the particle size of raw and auxiliary materials was analyzed by Raman imaging technology;the crystal habit and crystal form of active pharmaceutical ingredient(API)were characterized by the optical microscope and X-ray powder diffraction technology, respectively;the preparation process of reference listed drug was determined by disintegration method;and finally, the package material was identified by the morpholine reagent. Moreover, three batches of samples were pre-pared according to the determined prescription and process, and the quality was compared with the reference listed drug. Results: By the reverse engineering analysis of the reference listed drug, the prescription composition of the reference listed drug was determined to be composed of glucose, microcrystalline cellulose, pregelatinized starch, maltodextrin, magnesium stearate, colloidal silica and yellow lake, in which the glucose content was 32% and the microcrystalline cellulose content was <23%. The API crystal form of the reference listed drug was consistent with that of the self-made preparation. The average particle size of caffeine, microcrystalline cellulose, glucose, maltodextrin and pregelatinized starch was approximately 206, 112, 172 and 61 μm, respectively. The tablet preparation process was the direct compression method, and the packaging material was polyvinyl chloride aluminum foil. The quality of the three batches of home-made preparations was the same as that of the reference listed drug. Conclusion: Caffeine tablets with the same quality as Good Sense Stay Awake® were successfully prepared by reverse engineering of the reference listed drug, which provides a reference for the application of reverse engineering in the generic drug development and consistency evaluation.