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. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:2029-2036, 2007