X-ray powder diffractometry of intact film coated tablets - An approach to monitor the physical form of the active pharmaceutical ingredient during processing and storage

The antiviral compound, 2-amino-6-(4-methoxyphenylthio)-9-[2- (phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl)ester (MCC-478), can exist in several anhydrous polymorphic forms and also as a hemihydrate. The XRD patterns of the tablets, containing each form of the active pharmaceutical ingredient (API), revealed at least one peak unique to each form. A semiquantitative microdiffractometric method was developed to nondestructively characterize the physical form of the API in intact film-coated tablets. This was accomplished even though the weight fraction of the API was <0.2 and that of mannitol, a highly crystalline excipient, was ∼0.6. The method was used to determine the effect of aqueous film-coating process on the physical form of the API. The final dosage form was also monitored following storage at 40°C/75% RH for 6 months. There was no phase transformation of the API either due to the film-coating process or following accelerated storage. This technique has potential utility not only for process control during manufacture, but also for the quality control of the final product.