The complex microstructure of pharmaceutical creams

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Creams intended for topical application are multi-component oil-in-water emulsions widely studied and widely used in the pharmaceutical, veterinary, cosmetic, food, and personal care product industries. Many of these products incorporate as many as 20 excipients. Whilst it is known that some of the excipients contribute to the formation and stability of the creams, it is not clear what changes in the microstructure of the systems might be caused by additives like preservatives, active pharmaceutical ingredients, antioxidants, etc., and it is not known how such changes might affect the creams’ stability and functional properties. There is no real structure-based rationale employed in the formulation of creams, therefore, and new products are developed following only a semi-empirical formulation strategy.
The current lamellar network model of cream structure was proposed on the basis of the findings from experiments involving microscopy, rheology, differential scanning calorimetry, X-ray scattering, and thermogravimetric analysis. According to this model, the dispersed oil droplets are surrounded and stabilized by a monolayer of surfactant/co-surfactant (emulsifier) that keep the droplets dispersed through repulsive/steric forces, with the emulsifier in excess of that required to form these monomolecular films going to form a para-crystalline network of bilayers that trap water and thereby enhance the viscosity and give “body” to the cream. These structural details have generally been inferred, however, and not determined directly.
In this research, the molecular structure of creams was probed directly, making extensive use of small angle neutron scattering and exploiting hydrogen/deuterium contrast-variation. Additional studies were also performed using microscopy, rheology, small-angle and wide-angle X-ray scattering, and molecular dynamics simulations. The structural loci and arrangement of the excipients in different cream formulations were determined and these were then related to the macroscopic properties of the creams. The studies were first performed on different versions of an Aqueous Cream B.P. formulation containing liquid paraffin as oil, water, sodium dodecyl sulfate as surfactant, and a blend of hexadecanol and octadecanol as co-surfactants. The studies were then extended to cover a more complex, commercial, oil-free system, Physiogel® ‒ a formulation based on natural phospholipids combined with long chain fatty acids and alcohols. A comprehensive analysis of the microstructure of this system was made using neutron and X-ray scattering experiments as well as molecular dynamic simulations, alongside a series of microbiology experiments to understand the influence of preservatives on both the microstructure and functional properties of the systems.
As a consequence of these studies, it has been shown how different compositions of creams give rise to quite different internal architectures, and how changes in their formulation can alter their long-term stability and in-use properties.
Date of Award1 Feb 2021
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorDavid Barlow (Supervisor) & Margaret Lawrence (Supervisor)

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