Polymorphism in Commercial Sources of Fusidic Acid: A Comparative Study of the In Vitro Release Characteristics of Forms I and III from a Marketed Pharmaceutical Cream.

Jonathan Byrne,Robert Reinhardt,Trinidad Velasco-Torrijos

doi:10.1155/2017/3493096

Jonathan Byrne, Robert Reinhardt + Show 1 more

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https://doi.org/10.1155/2017/3493096

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Abstract

A comparison of the polymorphic forms of 3 commercial sources of fusidic acid using FTIR and XRPD techniques has been performed in this study. It has been demonstrated that polymorphic Forms I and III are currently available on the commercial market. The influence of the observed polymorphism on the stability of the drug substance in bulk form has been investigated through stability and stress testing according to current ICH guidelines. Significant differences were detected between commercial sources with regard to the stability of the bulk substance under photolytic and humidity stress conditions. When properly packaged in an inert atmosphere, fusidic acid from all 3 manufacturers showed a comparable stability. The effects of the observed polymorphic differences on the intrinsic dissolution rate of the drug substance and its in vitro release from the marketed drug product Fusicutan® plus Betamethasone cream have been investigated. Results indicated that the release rate of the drug substance is similar for polymorphic Forms I and III, allowing both forms to be used during manufacture without affecting the safety or efficacy of the drug product.

Highlights

Fusidic acid (FA, Figure 1(a)) is one of 18 naturally occurring triterpene compounds of fungal origin [1] which collectively make up the Fusidane group of antibiotic substances [2]
FA is mainly used in the treatment of Gram-positive bacterial infections (e.g., infected atopic dermatitis, Figure 1(b)), those caused by Staphylococcus species [2, 5, 6], and functions by binding to prokaryotic elongation factor G (EF-G), effectively stalling the elongation step of bacterial protein synthesis [7,8,9]
The results of the present study indicate that there are at least 2 polymorphic forms of fusidic acid (I and III) currently available on the commercial market

Summary

Introduction

Fusidic acid (FA, Figure 1(a)) is one of 18 naturally occurring triterpene compounds of fungal origin [1] which collectively make up the Fusidane group of antibiotic substances [2]. It is the most potent member of this group and is, to date, the only representative to have been used clinically [2]. FA is mainly used in the treatment of Gram-positive bacterial infections (e.g., infected atopic dermatitis, Figure 1(b)), those caused by Staphylococcus species [2, 5, 6], and functions by binding to prokaryotic elongation factor G (EF-G), effectively stalling the elongation step of bacterial protein synthesis [7,8,9]. The past decade has seen renewed interest in this drug as a treatment for methicillinresistant Staphylococcus aureus (MRSA, Figure 1(c)) [11,12,13,14,15,16] which can in part be attributed to its low toxicity and to the low incidence of resistance to FA in relevant bacterial populations [14, 15]

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