Study of compression effect on testosterone tablets.

Abstract

Objective: To analyze drug's physicochemical properties and dissolution profiles of testosterone tablets compressed with two different load levels (2 and 15 tons) and to evaluate the influence of process additive on tablet properties.

Significance: Testosterone implants are inserted in the subcutaneous tissue and follow a superficial erosion process that leads to drug absorption during 4 to 5 months. Testosterone is a cholesterol derivative with an anhydrous form as their most stable structure, although another two hydrated polymorphic forms were also identified. Due to the fact that compression processes may induce polymorphic changes in some API, which can lead to different dissolution behavior, a study of physicochemical properties and polymorphic changes are important to tablet manufacturing.

Methods: Tablets were manufactured by compression molding with a hydraulic press and analyzed by DSC, XRD, SEM, FTIR and drug dissolution tests.

Results: It was observed that 15 tons represented an excessive load, resulting in a fragile tablet with lamination and cracks. DSC analysis indicated the presence of structural water, although XRD patterns indicated that the drug was in its anhydrous form. FTIR also revealed water presence, but not an indicative of a monohydrate structure. Dissolution tests suggested the applied load and process additive may have some minor influence on dissolution profile, although they are not the main attributes influencing tablet dissolution.

Conclusions: This study provides insight on how compression load and process additive influences API properties and tablet behavior, showing the importance of these factors while developing a tablet manufacturing process.