Dissolution test for oral suspension: an overview about use and importance

Abstract This work aims to ascertain the comprehensiveness of dissolution tests for oral suspensions registered in Brazil and the USA. After consulting literature since 1994, a paucity of information about dissolution methods for suspensions was detected. It makes it difficult to establish the most appropriate test parameters. In January, 2019, there were 46 drugs registered in Anvisa (Brazil) as oral suspension, being 47 reference, 173 generic and 114 interchangeable similar (IS) medicines; while in the USA, 90 drugs were registered as oral suspension by FDA, 235 Abreviatted New Drug Application and 111 New Drug Application medicines. Out of 46 and 90, only six and 15 drugs as oral suspension had a pharmacopeial dissolution test, corresponding to 70 (20.9%) and 82 (23.7%) products in Brazil and the USA, respectively. Dissolution studies were found for 17 drugs as oral suspension in the non-compendial literature. Dissolution test conditions were established to few marketable oral suspension drugs, most of which are BCS class II or IV. Thus, investing in dissolution studies could subsidize the registration of these products by regulators, especially for generic and IS drugs, by comparing dissolution profiles, and predicting their in vivo behavior to avoid exposure of healthy individuals to clinical research.

Cost-Effectiveness of Point-of-Care A1C Tests in a Primary Care Setting.

Objective: We evaluated the cost-effectiveness of the point-of-care A1c (POC-A1c) test device vs. the traditional laboratory dosage in a primary care setting for people living with type 2 diabetes. Materials and Methods: The Markov model with a 10-year time horizon was based on data from the HealthRise project, in which a group of interventions was implemented to improve diabetes and hypertension control in the primary care network of the urban area of a Brazilian municipality. A POC-A1c device was provided to be used directly in a primary care unit, and for a period of 18 months, 288 patients were included in the point-of-care group, and 1,102 were included in the comparison group. Sensitivity analysis was performed via Monte Carlo simulation and tornado diagram. Results: The results indicated that the POC-A1c device used in the primary care unit was a cost-effective alternative, which improved access to A1c tests and resulted in an increased rate of early control of blood glucose. In the 10-year period, POC-A1c group presented a mean cost of US$10,503.48 per patient and an effectiveness of 0.35 vs. US$9,992.35 and 0.09 for the traditional laboratory test, respectively. The incremental cost was US$511.13 and the incremental effectiveness was 0.26, resulting in an incremental cost-effectiveness ratio of 1,947.10. In Monte Carlo simulation, costs and effectiveness ranged between $9,663.20-$10,683.53 and 0.33-0.37 for POC-A1c test group, and $9,288.28-$10,413.99 and 0.08-0.10 for traditional laboratory test group, at 2.5 and 97.5 percentiles. The costs for nephropathy, retinopathy, and cardiovascular disease and the probability of being hospitalized due to diabetes presented the greatest impact on the model's result. Conclusion: This study showed that using POC-A1c devices in primary care settings is a cost-effective alternative for monitoring glycated hemoglobin A1c as a marker of blood glucose control in people living with type 2 diabetes. According to our model, the use of POC-A1c device in a healthcare unit increased the early control of type 2 diabetes and, consequently, reduced the costs of diabetes-related outcomes, in comparison with a centralized laboratory test.

Equilibrium solubility study to determine fexofenadine hydrochloride BCS class and challenges in establishing conditions for dissolution profiles applied to suspension

The aim of this work was to perform solubility studies for fexofenadine hydrochloride and establish dissolution conditions for this drug in oral suspension dosage form. The solubility study was executed through the shake-flask method, below 37 ºC±1 ºC, at 100 rpm stirring for 12 h in three buffer solutions: hydrochloric acid pH 2.0, acetate pH 4.5 and phosphate pH 6.8. The dissolution test was developed in vessels containing 900 mL of the same buffer, employing the paddle apparatus in speed of 25 and 50 rpm, below 37 ºC±0.5 ºC. The drug was classified as low solubility according to the Biopharmaceutics Classification System, since the dose/solubility ratio was higher than 250 mL in all media tested (326.55 mL in buffer pH 2.0; 2,456.33 mL in buffer pH 4.5 and 1,021.16 mL in buffer pH 6.8). The dissolution test showed that a release of 85% in 30 min could be established. The rotation speed of 25 rpm, media volume of 900 mL and insertion of the samples through weighted syringes are adequate. The buffered media pH 2.0 could be chosen as dissolution media.