Prediction of drug solubility in an acrylate adhesive based on the drug-polymer interaction parameter and drug solubility in acetonitrile.

This paper describes the correlation of drug solubility in isooctyl acrylate/acrylamide/vinyl acetate (IOA/ACM/VOAc, 75:5:20) adhesive with a relative drug-polymer interaction parameter. This parameter, defined previously as the amount of molecules (Ln) sorbed onto the adhesive when swollen by acetonitrile (ACN) [J. Controlled Release 82 (2002) 1], represents the differential interaction of drug with the adhesive relative to ACN. When the drug solubility in the adhesive (Ln) and ACN (Ln) are used to describe drug-polymer and drug-ACN interactions, the following linear relationship is expected: Ln=Ln(0)+pLn+qLn (p and q are coefficients). This model is evaluated by the drug solubility in the adhesive measured by differential scanning calorimetry (DSC), and drug solubility in ACN. It is concluded that there is an excellent linear relationship for the parameters involved. As a result, the model can be used to compute the solubility in the polymer for new drug candidates. Moreover, the amount of sorbed molecules and solubility in ACN can be either easily measured or computed based on their molecular properties.

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