The impact of fumed silica on theophylline anhydrous under various humidities
Abstract
The impact of excipients with high water affinity on the physical and chemical stability of a moisture sensitive active ingredient was evaluated. The active drug, theophylline anhydrous, was mixed with one or more excipients and subjected controlled humidity conditions for 30 to 120 days. X-ray diffraction was performed on the blends following storage in order to determine the conversion of theophylline anhydrous to theophylline monohydrate. Conversion of theophylline anhydrous to theophylline monohydrate was evaluated based on excipients present in the formulations. Two diluents, hydrous lactose and dicalcium phosphate dihydrate, were utilized, either alone or in combination. Polyvinylpyrrolidone, a binder in wet granulation processes, and fumed silica, a glidant and moisture scavenger, were also included in several blends. Both polyvinylpyrrolidone and fumed silica have high moisture affinity and are able to bring moisture into a formulation. The ability of these excipients to preferentially adsorb moisture in a formulation and protect theophylline anhydrous from hydration was addressed in this study. The formulations were found to have predictable results based on the excipients used. The type of diluent used in formulations containing fumed silica was found to be of particular importance. The role of the excipients may also have a great effect on properties affecting tablet production. In order to determine if the blends studied would have properties allowing them to be easily tableted, functional parameters affecting powder flow were evaluated. The Carr Flowability Indices were utilized for this evaluation.
Degree
Ph.D.
Advisors
Peck, Purdue University.
Subject Area
Pharmaceuticals
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