The role of hydrophilic/hydrophobic group ratio of polyvinyl alcohol on the miscibility of amlodipine in orodispersible films: From molecular mechanism study to product attributes.

The miscibility of the therapeutic drug in the polymer matrix is the key to the successful design and development of orodispersible films (ODFs). In the present study, four hydrolyzed polyvinyl alcohols (PVAs) with identical polymerization degree were investigated as carriers for Amlodipine (AML) ODFs systematically. The drug-polymer miscibility and the intermolecular interaction were investigated by Flory-Huggins theory, Gordon-Taylor theory, molecular simulation, FTIR, Raman and H NMR. The product attributes of ODFs were also studied. A pharmacokinetic study in rats was then conducted using the film product of PVA5-72, the best performer tested. The results revealed that the drug-polymer miscibility decreased linearly with the increase of hydrolyzed degree of PVA. Hydrogen bonds formed between the drug and the hydrophilic and hydrophobic groups of PVAs were the main intermolecular interaction that caused the differences in drug-polymer miscibility. Furthermore, drug-polymer interaction influenced the product attributes of ODFs, including dissolution profile, mechanical properties and physical stability. The pharmacokinetic study showed the ODFs disintegrated rapidly, and the amorphous AML dissolved and absorbed in the gastrointestinal tract, which was comparable to the commercial product. The research offered a foundation for development scientists in designing and formulating PVA films.