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The aim of this work was the development and characterization of a biocompatible microemulsion ( ME) containing soybean oil ( O), phosphatidylcholine/sodium oleate/ Eumulgin® HRE40 as the surfactant mixture ( S) and water or buffer solution as the aqueous phase ( W), for oral delivery of the poorly water-soluble drugs sulfamerazine ( SMR) and indomethacin ( INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3535-3543, 2015 [ABSTRACT FROM AUTHOR]

• Clarithromycin solid forms were studied. • Exhaustive characterization in solid state was realized. • The physical stability was evaluated. Some polymorphic drugs may undergo solid-state transformations as a result of storage and manufacturing processes, which could have a significant impact on the performance characteristics of the drug. The present study was conducted as a strategy to provide information on clarithromycin polymorphs. The exhaustive characterization of solid form 0, an ethanol solvate, was performed starting with the development of a new synthesis route. The structural characterization was carried on by comparing the form 0 with the form II, the one currently used on the market. A variety of techniques, such as solid state nuclear magnetic resonance, X-ray powder diffraction, infrared spectroscopy, thermoanalytical methods and confocal microscopy, were used to identify the form 0. These studies revealed important intermolecular interactions, as well as certain spatial and morphological particularities. The biopharmaceutical properties including solubility in water and simulated gastric fluid, and microbiological performance were investigated. The physical stability under normal storage conditions during 15 months was examined, revealing a desolvation process and a subtle polymorphic transformation. The studies performed on the ethanol solvate of clarithromycin could prove to be a useful tool for assays used to ensure that the drug quality remains without changes in the final dosage product. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The main objective of this work was to study an inclusion complex between enalapril (ENA), and β-cyclodextrin (β-CD). From nuclear magnetic resonance (NMR) we determined that the complex showed a 1:1 stoichiometry, with an apparent formation constant (K C) of 439 and 290M−1 for the cis and trans isomers, respectively. The molecular modeling and NMR techniques demonstrated that the aromatic moiety of ENA was inserted into the hydrophobic cavity of β-CD. When studying the chemical stability of ENA complexed to β-CD, a clear stabilizing effect was observed in both the aqueous solution and solid state. [Copyright &y& Elsevier]

Abstract This investigation presents the characterization and evaluation of the physicochemical and microbiological properties of a new multicomponent complex of ketoconazole. Complex formation of the drug, with proline and β-cyclodextrin, was evaluated using nuclear magnetic resonance and phase solubility studies. The complex, in solid state, was prepared through kneading and physical mixture and then characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy. By means of confocal laser scanning microscopy, the effect of proline on the morphology of Candida albicans was evaluated. Microbiological assays were performed to evaluate the antifungal activity of the complex against C. albicans. The results obtained from phase solubility assays showed that the complexation of ketoconazole is an effective strategy to enhance its solubility. Confocal laser scanning microscopy demonstrated that proline severely affected Candida morphology, and microbiological studies established high antifungal activity for the complex, signifying an advantage, and therefore, a potential improvement in its application areas. Graphical abstract Image Highlights • KET complex with β-cyclodextrin and Proline was prepared and characterized. • The water solubility of KET was improved. • The antifungal activity was increase by multicomponent complex formation. • The multicomponent complex results a good candidate to optimize KET formulations. [ABSTRACT FROM AUTHOR]

Abstract: In order to enhance the ocular bioavailability of acetazolamide (ACZ), a multicomponent complex with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and triethanolamine (TEA) was prepared to be applied topically. In vitro corneal permeation across isolated rabbit cornea of proposed ACZ formulations and the marketed AZOPT® formulation (1% w/v brinzolamide) was studied. Formulations were also tested for their effect on the intraocular pressure (IOP) in rabbits. 1H- and 13C-NMR experiments were undertaken to verify the real inclusion of ACZ in the ACZ–HP-ß-CD–TEA multicomponent complex. The binding of ACZ to HP-ß-CD in the presence of TEA is described. The increase of TEA concentration decreases the apparent equilibrium constant for the ACZ–HP-ß-CD complex. The ternary system ACZ–HP-ß-CD–TEA seemed to be able to reduce IOP in about 30%. This effect was sustained for 4 h after instillation. In vitro corneal permeation studies demonstrated that the ACZ permeation was increased. RMN experiments indicated that TEA can weaken the association between ACZ and HP-ß-CD increasing the drug ocular hypotensive effect by increasing the free drug available for absorption. Our formulations were considered practically non-irritant. These results indicate that the ternary system ACZ–HP-ß-CD–TEA might be a useful tool for formulating aqueous ACZ eye drop solutions. [Copyright &y& Elsevier]

• Novel binary systems of albendazole desmotropes were studied. • Different molecular interactions between each desmotrope and aminoacids were established. • The interactions were analyzed by NMR and molecular modeling studies. • Solid samples were characterized. • Aminoacids can be used as green strategies in the pharmaceutical industry. In this work, new binary systems of albendazole desmotropes with amino-acids were developed and investigated. In particular, solubility studies evidenced that aspartic acid and glutamic acid were the most important enhancer ligands. The molecular interactions were examined by nuclear magnetic resonance and molecular modeling techniques, which revealed that the binary systems are stabilized by several intermolecular H-bonds. Solid samples were prepared by kneading method and physical mixture. It was characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, thermal analysis and solubility studies. The results obtained showed that the binary systems significantly incremented the saturation solubility in water and simulated gastric fluid compared to free desmotrope. In conclusion, the enhancement of biopharmaceutical properties evidenced that these novel systems are promising candidates for the development of oral formulations for delivery of the drug. [ABSTRACT FROM AUTHOR]

• Four solid forms of oxytetracycline hydrochloride were obtained. • Exhaustive characterization in solution and solid state was realized. • The polymorphism does not affect the antimicrobial activity of the drug. Oxytetracycline hydrochloride, an antibiotic of the tetracycline family, is a polymorphic drug that evidences erratic absorption in oral administration. Additionally, poor solid state characterization of the polymorphs and diversity in the existing nomenclature impede the correct identification of the raw materials. In this work, oxytetracycline hydrochloride solid forms were prepared from isopropyl alcohol, ethanol and methanol through different crystallization techniques, and then their physicochemical and microbiological properties were evaluated. A combination of advanced techniques such as solid state nuclear magnetic resonance, powder X-ray diffraction, infrared spectroscopy, thermal analysis, scanning electron microscopy and energy-dispersive X-ray spectroscopy were used in the characterization of solid samples giving clear evidence of the existence of three stable and one metastable solid forms of the oxytetracycline hydrochloride. Solubility was determined in aqueous solution, simulated gastric fluid, and simulated intestinal fluid. In addition, microbiological studies were performed. The polymorphs showed similar antimicrobial activity against Escherichia coli and Staphylococcus aureus. Therefore, these solid forms of oxytetracycline hydrochloride constitute promising candidates to encourage studies for repositioning old and known antibiotic drugs in the developing strategies for new therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Novel ternary systems with β-cyclodextrin or maltodextrin and triethanolamine as the third component were developed with the aim of improving the oral bioavailability of furosemide. These new solids were characterized by solid-state nuclear magnetic resonance, Fourier transform infrared and Raman spectroscopy, X-ray powder diffractometry, scanning electron microscopy, thermogravimetric analysis, and differential scanning calorimetry. The solubility, dissolution and stability (chemical and physical) were studied. Among the most important results, it was observed that both ternary systems showed an important enhancement in the solubility of the drug. In particular, the system obtained by combination of β-cyclodextrin and TEA exhibited improvement in the dissolution profiles and photo-stability of furosemide compared with the binary system previously reported. Moreover, this system constitutes an interesting therapeutic alternative as it did not produce cellular toxicity compared with free furosemide. In conclusion, the results obtained revealed that this ternary system establishes a promising approach for oral delivery of the drug. • Ternary systems enhanced the biopharmaceutical properties of furosemide. • Furosemide, one oligosaccharide and triethanolamine were combined. • The best oligosaccharide as candidate for the systems was β-cyclodextrin. • The system obtained using β-cyclodextrin and TEA did not produce cellular toxicity. [ABSTRACT FROM AUTHOR]