ABSTRACT
A solvate cocrystal of the antimicrobial norfloxacin (NFX) was formed by using isonicotinamide (INA) as a coformer with the solvent evaporation technique. The cocrystal formation was confirmed by performing solid-state characterization techniques. We evaluated the dissolution under supersaturated conditions and also the solubility at the vertex of triphasic domain of cocrystal and NFX in both water and Fasted-State Simulated Intestinal Fluid (FaSSIF). The antimicrobial activity was evaluated using the microdilution technique. The cocrystal showed 1.8 times higher dissolution than NFX in water at 60 min and 1.3 times higher in FaSSIF at 180 min in the kinetic study. The cocrystal also had an increase in solubility of 8.38 times in water and 6.41 times in FaSSIF. The biopharmaceutical properties of NFX with cocrystallization improved antimicrobial action, as shown in the results of minimum inhibitory concentration (MIC) and inhibitory concentrations of 50% (IC50%) and 90% (IC90%). This paper presents, for the first time, a more in-depth analysis of the cocrystal of NFX-INA concerning its dissolution, solubility, and antimicrobial activity. In all these criteria, the cocrystal obtained better results compared to the pure drug.
ABSTRACT
Cocrystals have gained attention in the pharmaceutical industry due to their ability to improve solubility, stability, in vitro dissolution rate, and bioavailability of poorly soluble drugs. Conceptually, cocrystals are multicomponent solids that contain two or more neutral molecules in stoichiometric amounts within the same crystal lattice. There are several techniques for obtaining cocrystals described in the literature; however, the focus of this article is the Reaction Crystallization Method (RCM). This method is based on the generation of a supersaturated solution with respect to the cocrystal, while this same solution is saturated or unsaturated with respect to the components of the cocrystal individually. The advantages of the RCM compared with other cocrystallization techniques include the ability to form cocrystals without crystallization of individual components, applicability to the development of in situ techniques for the screening of high quality cocrystals, possibility of large-scale production, and lower cost in both time and materials. An increasing number of scientific studies have demonstrated the use of RCM to synthesize cocrystals, mainly for drugs belonging to class II of the Biopharmaceutics Classification System. The promising results obtained by RCM have demonstrated the applicability of the method for obtaining pharmaceutical cocrystals that improve the biopharmaceutical characteristics of drugs.
ABSTRACT
The impact of thyroid hormone (TH) disorders on male reproductive biology has been a controversial issue for many years. Recently, we reported that hypothyroid male rats have a disruption of the seminiferous epithelium, which may compromise spermatogenesis. To improve the understanding of the reproductive pathogenesis of hypothyroidism and hyperthyroidism, male Wistar rats that developed these dysfunctions in adulthood were used as an experimental model. We evaluated the sperm production, reserves, transit time, morphology, and functionality (acrosome integrity, plasma membrane integrity, and mitochondrial activity), and the testicular expression of the TH receptors (Thra1 and Thra2, Thrb1, and Thrb2), deiodinases (Dio2 and Dio3), and the Mct8 transporter (Slc16a2) were assessed by reverse transcription followed by real-time quantitative PCR (RT-qPCR). The results were evaluated statistically by ANOVA and Tukey HSD test (P < 0.05). Hypothyroidism decreased the total and daily sperm productions and increased the sperm transit time through the epididymis, while the sperm functionality was reduced in both thyroid dysfunctions. Regarding the modulation of gene expression in the testis, hypothyroidism increased the expression of Thra1 and decreased the expression of Dio3, and hyperthyroidism increased the expression of Slc16a2. The observed alterations in spermatic production and function and in the expression of the TH receptor, deiodinase, and the TH transporter are suggestive of TH participation in spermatogenesis in adulthood.
