The solubility of flurbiprofen in Witepsol H15, a semi-solid wax matrix, was determined using microscopy, Higuchi release rates and HyperDSC (high speed differential scanning calorimetry); solubility values of 20-30% w/w, 9.56% w/w and 20.13% w/w resulted from the three techniques, respectively. Microscopy was useful in additionally examining crystal size, shape and distribution. Release rate experiments showed that release from these formulations followed Higuchi kinetics with an inflection in release rate constant at the drug loading corresponding to drug solubility. HyperDSC not only measured solubility but also determined the melting point of the formulation. The results from microscopy and HyperDSC correlated well with release kinetics providing a much lower solubility value. Higuchi release kinetics are based on release from liquids and ointments whereas melting waxes provide a more complex system which may account for the variation in solubility estimation using this technique. This study further demonstrated the use of HyperDSC as a robust, high throughput technique to measure the solubility of a drug in a semi-solid.
- Higuchi kinetics