The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.

Background: Solubility, intestinal permeability and dissolution are the main factors that govern the rate and extent of drugs absorption and are directly related to bioavailability. Biopharmaceutics Classification System (BCS) is an important tool which uses in vitro results for comparison with bioavailability in vivo (biowaiver). Valsartan is widely used in the treatment of hypertension and shows different BCS classification in the literature (BCS class II or III). Objective: This work proposes the study of valsartan biopharmaceutics properties and its BCS classification. Methods: High Performance Liquid Chromatography (HPLC) method was developed and validated to quantify the drug in buffers pH 1.2, 4.5 and 6.8 respectively. Valsartan solubility was determined in these three different media using shake flask method and intrinsic dissolution rate. Evaluation of dissolution profile from coated tablets was conducted. Results: The low solubility (pH 1.2 and 4.5) and high solubility (pH 6.8) were observed for both solubility methods. Permeability data reported from the literature showed that valsartan is a low permeability drug. Valsartan presented the rapid release profile only in pH 6.8. Conclusion: We defined that valsartan is a class IV drug, in disagreement with what has been published so far. It is important to emphasize that the conditions considered here are indicated to define the biopharmaceutics classification by regulatory agencies.

Objectives: Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. Methods: Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. Key findings: Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10−6 cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10−6 cm/s). Conclusions: The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate.