title: Application of surface area measurement for identifying the source of batch-to-batch variation in processability.
abstract: The primary goal of this study was to evaluate the use of specific surface area as a measurable physical property of materials for understanding the batch-to-batch variation in the flow behavior. The specific surface area measurements provide information about the nature of the surface making up the solid, which may include defects or void space on the surface. These void spaces are often present in the crystalline material due to varying degrees of disorderness and can be considered as amorphous regions. In the present work, the specific surface area for 10 batches of the same active pharmaceutical ingredient (compound 1) with varying quantity of amorphous content was investigated. Some of these batches showed different flow behavior when processed using roller compaction. The surface area value was found to increase in the presence of low amorphous content, and decrease with high amorphous content as compared to crystalline material. To complement the information obtained from the above study, physical blends of another crystalline active pharmaceutical ingredient (compound 2) and its amorphous form were prepared in known proportions. Similar trend in specific surface area value was found. Tablets prepared from known formulation with varying amorphous content of the active ingredient (compound 3) also exhibited the same trend. A hypothesis to explain the correlation between the amorphous content and specific surface area has been proposed. The results strongly support the use of specific surface area as a measurable tool for investigation of source of batch to batch variation in processability.
authors.affiliation: Pharmaceutical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey 07936, USA. radha.vippagunta@novartis.com
authors.forename: Radha R
authors.initials: RR
authors.lastname: Vippagunta
authors.forename: Changkang
authors.initials: C
authors.lastname: Pan
authors.forename: Ronak
authors.initials: R
authors.lastname: Vakil
authors.forename: Vindhya
authors.initials: V
authors.lastname: Meda
authors.forename: Richard
authors.initials: R
authors.lastname: Vivilecchia
authors.forename: Michael
authors.initials: M
authors.lastname: Motto
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D013499:Surface Properties; D013607:Tablets / Q000032:analysis*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D013607:Tablets; D014867:Water