Alteration of gel point of poloxamer 338 induced by pharmaceutical actives and excipients.

Abstract

Poloxamer 338 is used as versatile thermo-responsive gelling agent in topical and sub-cutaneous applications. Due to application specific needs a gel point below body or even below room temperature is required. The influence of inorganic salts and active pharmaceutical ingredients (APIs) on the gel point was investigated using oscillatory rheology to identify the driving forces and predictors for gel point alteration. While most inorganic salts decreased the gel point, API salts exhibited an increase. Consistent with previous findings, the extent of gel point alteration caused by inorganic salts could be empirically described by the Hofmeister series, primarily influenced by the anion. Notably, this study revealed a concentration-dependent increase in the gel point in the presence of API salts. Moreover, this increase could be accurately predicted in a linear manner by considering the respective logP value. By utilizing the proposed prediction model, the effect of API addition on the gel point can be estimated, facilitating formulation development to achieve the desired gelling behavior for specific applications.