The influence of formulation and processing variables on the phytochemical profile of Hypericum perforatum extract

Abstract

Objective. St. John's Wort's (SJW) complex composition-activity relationship presents a major challenge in developing dosage forms (df) that exhibit appropriate quality and performance. To attempt to meet this challenge, this research examined: (1) selected physicochemical properties of commercial SJW extracts; (2) how certain excipients and processing parameters may affect the phytochemical profile (PP); (3) the utility of similarity metrics in summarizing PPs, and; (4) formulated SJW capsule df performance. Methods. An adapted analytical method was developed and used to compare PPs of commercial extracts and assess their stability and compatibility. Modifications to conventional isothermal stress testing paradigms were explored. Formulated SJW capsules and tablets were prepared to study any potential effect of compression force on PPs and the stability of formulations filled into gelatin and HPMC capsules. A gelatin capsule formulation was developed and tested for df performance per compendial methods. Results. The adapted analytical method proved suitable for assessing the phytochemicals of interest. Extracts exhibited similar total hypericins contents (marker compounds), but greatly different overall PPs. The extracts were moderately fluid, highly hygroscopic, and exhibited compression properties unlike those of typical fillers. Storage paradigms were suitable for excipient compatibility testing when controls of neat material are employed. Phytochemicals were not uniformly compatible with excipients. Malic acid did not stabilize the PP. Similarity metrics conveniently summarized changes to overall PP profiles. Some components in neat and formulated SJW were adversely influenced by tableting compressive forces. Phytochemicals had varying stability towards capsule shell composition and sealing: neat SJW typically was more sensitive. A capsule formulation of SJW was developed that easily surpassed compendial df performance specifications. Conclusion. This research provides guidance in formulating SJW dfs, and by analogy, other botanical dfs. Similarity metrics are recommended for summarizing the PP of botanicals when activity cannot be adequately represented by one or two marker compounds.