The influence of surfactants in drug release media: Towards bio-relevant media to mimic peritoneal fluid

Abstract

Introduction: Peritoneal fluid (PF) is produced by the peritoneum in the peritoneal cavity and functions as a physical barrier against infection and acts as a lubricant on the surface tissue lining the abdominal wall and pelvic cavity. The peritoneal cavity is an administration site for both conventional and controlled release formulations for the treatment of intestinal cancer, and in the management of post-operative pain and inflammation. Phosphate buffer saline (PBS) is a commonly used medium to simulate PF in drug dissolution studies. However, a recent study has shown significant differences between PF and PBS, where the rate of drug release in PF was faster than in PBS. The difference in surface tension between these two media is believed to be one of the causes of the difference in drug release rate. In this project we hypothesized that the addition of the surfactant sodium lauryl sulphate (SLS) to PBS will lower surface tension and increase the rate of drug release from a polymeric matrix. Lidocaine (Lido) and dexamethasone (Dex) were loaded into a polymer carrier in this project; these drugs are administered via the intra-peritoneal route as a local anaesthetic and anti-inflammatory, respectively. Aims: The main aim of this thesis was to reduce the surface tension of PBS to the levels seen in ex vivo human peritoneal fluid and to investigate the influence of this on drug release. The specific objectives of this research were to i) prepare poly ethylene-co vinyl acetate (EVA) films loaded with Lido and Dex, ii) determine how the addition of surfactant influences the surface tension of PBS and the contact angle between the EVA and PBS, and iii) determine drug release rates into PBS containing different amounts of surfactant. Conclusion: Lowering the surface tension through the addition of the surfactant SLS into PBS increased the rate of drug release in Dex at levels above 0.001% w/v SLS/PBS and in Lido at 0.005% w/v SLS/PBS which is above the CMC. The data generated in this study could be used in the future to develop bio relevant simulated peritoneal fluid for the in vitro testing of medicines designed for use in the peritoneal cavity. In order to achieve a bio relevant media properties in addition to surface tension also need to be considered such as pH and buffer capacity, osmolality, and viscosity.