Byrne, Jonathan (2018) Analytical Studies Concerning the Stability of Betamethasone Valerate and Fusidic acid Hemihydrate in Topical Pharmaceutical Preparations. PhD thesis, National University of Ireland Maynooth.

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Abstract

The research work presented in this thesis describes studies concerning the stability of the drug substances betamethasone 17-valerate and fusidic acid hemihydrate in topical pharmaceutical formulations. In particular, the work concentrates on formulation factors affecting the intra-molecular isomerisation of betamethasone 17-valerate to 21-valerate in a developmental topical cream for treatment of atopic dermatitis and psoriasis. Appropriate analytical tools for the simultaneous analysis of both drug substances have been developed and their suitability for use in the study demonstrated by validation experiments. The results of the isomerisation study indicate that the concentration of the emulsifier macrogolstearylether-21 significantly influences the isomerisation rate of the glucocorticoid. 5 % (w/w) of this substance in the formulation resulted in complete isomerisation within a number of months, whereas 1.5 % (w/w) gave rise to less than 3 % isomerisation after 3 years storage. The study data was used to develop a new topical drug formulation containing both betamethasone 17-valerate and fusidic acid which went to market in early 2017. Additionally, the influence of the polymorphic form of fusidic acid on its stability was investigated. Fusidic acid is known to exist in 4 polymorphic modifications and this study has shown that polymorphic forms I and III are currently available on the commercial market. Intrinsic dissolution – and in-vitro permeation studies demonstrate that both polymorphs have similar intrinsic dissolution rates, as well as comparable in-vitro release rates from the developmental cream. This indicates that both forms may be used interchangeably without affecting the safety and efficacy of concerned drug products. Finally, the plausibility of incorporating both drug substances into electrospun poly(caprolactone) (PCL) microfibers for potential use as an occlusive medicated dressing was examined. The effect of addition of the novel low molecular weight gelator, Fmoc-OH-C18, on the manufacture of the microfibers as well as on their in-vitro drug release rates was studied. The gelator was found to have a profound effect on the morphology of the resulting fibers but had little effect on the release rate of the active drug substances. The results suggest that the use of a medicated electrospun dressing containing betamethasone valerate and fusidic acid might be a viable treatment alternative to the current topical dosage forms. However, significant further work is needed in this regard.

Item Type:	Thesis (PhD)
Keywords:	Analytical Studies; Stability; Betamethasone Valerate; Fusidic acid Hemihydrate; Topical Pharmaceutical Preparations;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	10761
Depositing User:	IR eTheses
Date Deposited:	29 Apr 2019 16:42
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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