Development of Poly(2-oxazoline)s and poly(2-oxazine)s based formulation library and estimation of polymer/drug compatibility.

The main objective of this study is to formulate a library of difficult to solubilize drugs with four slightly different poly(2-oxazoline)s (POx) and poly(2-oxazine)s (POzi) based amphiphilic triblock copolymers and to elucidate whether the drug-polymer compatibility, as estimated by solubility parameters (SPs) might be used as tool to guide formulation development. The theoretical and experimental SPs of different homo-/triblock copolymers and 21 different hydrophobic drugs were calculated by two group contribution methods (i.e. Hoftyzer Van-Krevelen and Yamamoto molecular break method) and determined experimentally by solubility testing in list of selective solvents (for polymers only). The obtained SPs were further utilized to calculate the distance between polymers and drugs (Ra) in 3 dimensional Hansen space. Out of 21 structurally diverse drugs, the loading capacity (LC) was found to be higher than 40, 30, 20 and 10 wt.% for 4, 4, 3 and 5 drugs, respectively. In the remaining of 5 drugs the maximum achievable LC was found below 10 wt.%. The experimental results obtained by formulation development were not in accordance with the results predicted by Ra calculation. In contrast to several reports found in the literature, the determination of SPs and concurrent compatibility estimation appeared not to be a suitable tool to predict polymer-drug compatibility in the present system. As the predictive power of SPs is based on simple mathematical calculations, limiting the precise prediction of overall polarity, hydrogen bonding ability of molecules and interplay between the hydrophilic and hydrophobic domains resulting in differing deviations than predicted interactions thus might compromise the predictive power of HSPs.