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 approximately 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 degrees 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.
Yamada
Hiroyuki
H
Department of Pharmaceutics, University of Minnesota, 308 Harvard Street SE, Minneapolis, Minnesota 55455, USA.
Suryanarayanan
Raj
R
D000998:Antiviral Agents / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D005079:Excipients / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D011786:Quality Control; D013608:Tablets, Enteric-Coated / Q000032:analysis* / Q000737:chemistry; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods*
C461207:2-amino-6-(4-methoxyphenylthio)-9-(2-(phosphonomethoxy)ethyl)purine bis(2,2,2-trifluoroethyl) ester; D000998:Antiviral Agents; D005079:Excipients; D004364:Pharmaceutical Preparations; D011687:Purines; D013608:Tablets, Enteric-Coated; D014867:Water; D008353:Mannitol