Evaluation of the losartan solubility in the biowaiver context by shake-flask method and intrinsic dissolution.

This study aimed at evaluating the shake-flask use as a universal method to evaluate drug solubility in a biowaiver context as proposed by FDA, EMA and ANVISA. The solubility of losartan was determined in three buffers using the shake-flask method, intrinsic dissolution (ID) and Quantum Chemistry. Moreover, the evaluation of a losartan dissolution profile from coated tablets was conducted. The losartan low solubility in pH 1.2 and high solubility in pH 6.8 were observed using the shake-flask method. However, the solubility results using ID demonstrated its high solubility in pH 1.2 and 6.8. It was not possible to find conclusive results regarding the solubility of the drug in pH 4.5. The studies conducted by Quantum Chemistry provide molecular and electronic data that helped understand the losartan solvation in different pH values. Our experimental results defined that losartan can be classified as a low-solubility drug. In addition, this work shows that shake-flask cannot be a universal method of solubility studies in biowaiver context. Individual analysis will be necessary. The intrinsic dissolution should be considered as a complementary method.

Folic acid: a biopharmaceutical evaluation.

The aqueous solubility and drug product dissolution are important factors that determine the rate and extent of drug absorption from immediate release solid oral dosage forms. The aim of this article was to perform a folic acid biopharmaceutical study to evaluate the biowaiver of new products containing folic acid. We studied the solubility of its raw material and the dissolution profile of two commercially available products. Three different buffers (pH 1.2, 4.5 and 6.8) were used as the media of the solubility and dissolution tests (apparatus II, at 50 rpm and 900 mL of medium volume). We found that folic acid solubility and its release from tablets are pH dependent. The dissolution profiles of both tablets were compared by dissolution efficiency (%), using t-test or variance analysis (ANOVA). The dissolution profiles obtained for the two products at pH 1.2 medium were similar (p > 0.05), but they were dissimilar at pH 4.5 and 6.8 (p < 0.05). Furthermore, we could observe differences between all the dissolution profiles of folic acid for each product at three different dissolution media used. The results showed that physicochemical characteristics of folic acid affect its dissolution and absorption making it difficult to take a decision on their biowaiver based on BCS.