Method for predicting the solubility of a molecule in a polymer at a given temperature

摘要

The invention provides an improved method to predict the solubility of a drug or other molecule in a solid polymer or other matrix at any temperature. The instant invention provides a method to determine the difference in specific enthalpy, specific entropy and specific Gibbs energy between a solid solution and the unmixed components, as well as a method to use those data to predict the solubility of a drug or other molecule in a solid polymer or other matrix. The method uses known thermodynamics equations and thermal analysis data, such as obtained from DSC (differential scanning calorimetry) at temperatures that are lower than the temperature at which the solubility is predicted. The method allows prediction of the drug-in-polymer solubilities without the use of elevated temperatures, but still avoids impractically long experiments. The instant invention can predict the solubility at many temperatures, but is particularly useful in the pharmaceutical sciences to predict the solubility of a drug in a polymer at typical storage temperatures, which are typically near room temperature or below.

主权项

1. A method for determining the difference in specific enthalpies at a given temperature T and pressure due to heat content differences between a solid solution and unmixed components of the same composition, comprising
a) providing unmixed components of a substance and a polymer in a known weight ratio and at a given temperature; b) providing a solid solution mixture of said substance in said polymer in the same weight ratio at said temperature; c) obtaining the specific heats of said unmixed components using DSC or other appropriate method, from the lowest temperature for which data is used Tmin to said temperature T or higher; d) obtaining the specific heat of said solid solution using DSC or other appropriate method, from the lowest temperature for which data is used Tmin to said temperature T or higher; e) taking the difference between the specific heats of said solid solution and said unmixed components over the experimental range from Tmin to said temperature T or higher to construct a function ΔCP; f) providing an approximating function Δc that fits said experimental ΔCP data; g) calculating values of Δc for temperatures ranging from absolute zero to Tmin; h) determining the difference in specific enthalpy due to the heat content difference ΔHheat between said solid solution and said unmixed components from Eq. (31).