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Purpose: To evaluate the in vivo and in vitro behavior of amlodipine immediate release products. Methods: Three Mexican amlodipine products and the innovator (Norvasc®) were evaluated. Three bioequivalence studies were performed in 24 healthy male and female volunteers each. Plasma concentrations were determined using a liquid chromatographic method coupled with tandem mass spectrometry (LC/MS/MS). Dissolution profiles were evaluated using USP type apparatus 2 at 75 rpm and 500 mL of HCl 0.1N, pH 4.5 and pH 6.8. Also, the dissolution behavior of different lots of the innovator product was evaluated using apparatus 1 or 2 and 900 mL of buffer pH 6.8. Results: All the generic products under study were bioequivalent to the innovator. In vitro data showed that although at pH 1.2 and 4.5, the products met the specifications for very rapidly dissolving products but at pH 6.8, neither the innovator nor the test products complied with the criteria for rapidly dissolving products. When the study was performed at pH 6.8 in 900 mL of medium, the innovator showed a rapid dissolution behavior. Conclusion: The results show that the use of WHO conditions (900 mL of media, apparatus 2 at 75 rpm) are more adequate to predict the in vivo behavior of the amlodipine products.

The main objective of the present study was to develop a dissolution method for melatonin sublingual tablets. A factorial design type 2 was performed using agitation rate, dissolution media and sampling times as critical test parameters. For the experimental design, one commercial batch of the Mexican reference sublingual tablet product (5 mg) was used. The quantification of the drug released was performed using an UV assay at 220 nm. The best results were obtained using USP Apparatus 2 (paddles) at 50 rpm and 500 mL of water as dissolution medium. For the method evaluation, the dissolution profiles of two batches of a reference product and two batches of two commercially available melatonin generic products (5 mg) were evaluated and compared using a model-independent analysis. Results showed the capacity of the method to discern between different products of melatonin sublingual tablets. RezumatObiectivul principal al prezentului studiu a fost dezvoltarea unei metode de dizolvare pentru comprimatele sublinguale cu melatonină. A fost realizat un design factorial de tip 2 folosind viteza de agitare, mediul de dizolvare și timpii de reumplere ca parametri critici de testare. Pentru studiul experimental, a fost utilizat un lot comercial al produsului de referință din Mexic (5 mg). Cuantificarea substanței eliberate a fost efectuată utilizând o metodă UV la 220 nm. Cele mai bune rezultate s-au obținut folosind aparatul cu palete la 50 rpm și 500 mL apă ca mediu de dizolvare. Pentru evaluarea metodei, profilurile de dizolvare a două loturi de produs de referință și două loturi de două produse generice cu melatonină disponibile comercial (5 mg) au fost evaluate și comparate, utilizând o analiză independentă de model. Rezultatele au arătat capacitatea metodei de a discerne între diferite produsele ce conțin comprimate sublinguale cu melatonină.

Albendazole is a broad-spectrum anthelmintic drug used for parasitic infections. In addition, due to its mechanism of action, it has been studied as an anticancer agent. However, poor and highly variable bioavailability are limiting factors for its use in systemic illnesses. The present study aimed to develop two parenteral formulations of albendazole and to compare its pharmacokinetic profile with the conventional oral administration. Parenteral formulations were developed using two different approaches: a phosphonooxymethylated prodrug and cosolvents. For the albendazole prodrug, once synthetized, its solubility and hydrolysis with alkaline phosphatase were evaluated. A factorial design of experiments was used for the cosolvent formulation. Stability and hemolytic activity were assessed. A pharmacokinetic study was performed on New Zealand rabbits. Both formulations were administered intravenously, and the prodrug was also administered intramuscularly. Results were compared with those obtained after the oral administration of albendazole. A 20,000-fold and 6000-fold increase in albendazole solubility was found with the prodrug and cosolvent formulations, respectively. Both parenteral formulations displayed higher albendazole plasma concentrations for the first 2 h compared with oral administration, even when the oral dose was doubled. The absolute bioavailability of oral albendazole was 15.5% while for the intramuscular administration of the prodrug was 102.6%. Both parenteral formulations showed a significant decrease in the formation of albendazole sulfoxide (ANOVA p<0.05) and allowed greater exposure to albendazole. Albendazole cosolvent parenteral formulation could be a promising option in systemic illnesses considering its ease of preparation and superb pharmacokinetic performance. Graphical abstract