(W1130-07-38) Sustainable Alternatives to Petroleum-Derived Excipients in Topical Creams

Purpose: Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) topical cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Though both mineral oil and petrolatum derive from mineral sources, with a well-known petrochemical origin, they are considered problematic ingredients from a sustainable point of view. Natural or synthetic excipients derived from vegetable sources could be explored as alternatives to petroleum-based excipients in prototype topical creams. This research aimed to investigate replacement or reduction in wax-type petroleum-based excipients, used as stiffening, emulsifying and/or stabilizing agents in pharmaceutical O/W creams, with sustainable or environmentally friendly ingredients. The physicochemical features and performance (drug release and skin permeation) of the emulsion-based creams were evaluated to determine if the sustainable excipients can provide similar properties as petrolatum-based creams.

Methods: In this study, different prototype O/W topical cream formulations, comprised of 1% w/w lidocaine and sustainable excipients were prepared and compared to a conventional cream comprised of petroleum-derived excipients in terms of key quality and performance attributes and physicochemical properties, such as globule size, rheology, Lumisizer phase separation index, and formulation performance using IVRT and IVPT.Refer to Figure 1 for a map of sustainable alternatives to conventional excipients.

Results: The physicochemical as well as performance attributes of both conventional and sustainable formulations are shown in Table 1. The petrolatum-based control formulation had the highest viscosity of 248.0 Pa·s, a melting point of 42.7°C, a low separation index at 25°C of 0.031, and an release rate of 52.9 µg/cm²/h. Formulation SUS-4 was the least viscous formulation at 86.9 Pa·s, had the lowest melting point of 33.6°C, the highest separation index of 0.120, and the highest release rate of 139.4 µg/cm²/h. Alternatively, SUS-5 had a higher viscosity of 131.3 Pa·s, a melting point of 43.6°C, a low separation index of 0.046, and the lowest release rate of 25.2 µg/cm²/h. The cumulative drug permeation after 12 h from SUS-4 and SUS-5 were found to be 126.2 µg/cm² and 113.8 µg/cm², respectively which were statistically similar to the control (108.1 µg/cm²). This result suggests that skin is indeed rate limiting for drug delivery, and permeation is independent of formulation compositions, microstructure and release profiles.

Conclusion: The physicochemical properties such as rheology and drug release rates of topical O/W creams were found to be greatly influenced by the differences in formulation composition; however, drug delivery through skin permeation was not impacted. Overall, sustainable natural or synthetic excipients in topical cream formulations were found to be suitable alternatives to petroleum-based excipients with comparable key quality attributes and performance attributes and should be considered during formulation development.

Acknowledgements: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this poster.

Figure 1. Replacement of conventional ingredients with more sustainable alternatives and approximate target % (w/w).

Table 1. Summary of formulation physicochemical and performance attributes.