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The aim of this study was to investigate the influence of the production method and the polymeric carrier on the ability to generate and maintain the supersaturation of a poorly soluble drug in biorelevant medium. The amorphous solid dispersion of sulfamethoxazole, an antibacterial drug, was produced using two different polymers by spray-drying or hot melt extrusion methods. When Eudragit EPO was used, supersaturation was maintained up to 24 h for both techniques at all drug-polymer proportions. However, when Soluplus was employed in hot melt extrusion, a smaller amount of drug was dissolved when compared to the amorphous drug. The proportion of 3:7 drug-Eudragit EPO (w/w) produced by spray-drying presented a higher amount of drug dissolved in supersaturation studies and it was able to maintain the physical stability under different storage conditions throughout the 90-day evaluation. Supersaturation generation and system stability were found to be related to more effective chemical interaction between the polymer and the drug provided by the production method, as revealed by the 1D ROESY NMR experiment. Investigation of drug-polymer interaction is critical in supersaturating drug delivery systems to avoid crystallization of the drug and to predict the effectiveness of the system. Chemical compounds studied in this article: Sulfamethoxazole (PubChem CID: 4539) and Methacrylate copolymer — Eudragit EPO (PubChem CID: 65358) [ABSTRACT FROM AUTHOR]

Background: The drug supersaturation in the intestinal lumen for few hours could result in high bioavailability. The goal of this study was the development of a supersaturating drug delivery system containing sulfamethoxazole and trimethoprim at fixed dose combination (sulfamethoxazole:trimethoprim 5:1 w/w). Methods: The amorphous solid dispersions were formed at three different proportions containing 30, 50 and 70% of Eudragit EPO in the formulation. Results: The supersaturation state is formed by the amorphous drugs produced by spray drying technique, and the maintenance of this state is due to the chemical interactions between the drugs and the polymer selected, which was observed in the fluorescence interaction studies realized between the drugs and the polymer. The Formulation containing 70% of the polymer was able to produce and maintain the supersaturated state of both drugs for 24 h. Solid state characterization demonstrated the amorphization of the drugs in the solid dispersion and indicated the hydrogen bond formation responsible for the improvement in the apparent solubility. This formulation presented an improved antibacterial activity when compared to the combination of the drugs. Conclusion: For the first time, a supersaturating drug delivery system was developed to the complementary antibacterial drugs. This ternary formulation is a powerful alternative to improve oral absorption of recognized safety drugs, reducing the dose and consequently the antibiotic resistance emergence. [ABSTRACT FROM AUTHOR]

Many drugs are abandoned due to poor aqueous solubility, although having a potential therapeutic effect. Numerous methods have been followed to improve the dissolution rate of poorly water soluble drugs. Solid dispersion is successfully applied to improve the solubility and consequently the bioavailability of poorly water soluble drugs. The aim of present study was to prepare solid dispersions of Pioglitazone HCl with PEG 6000, PVP, Poloxamer 407, Eudragit EPO and HPMC and determine the effect of those polymers on dissolution of pioglitazone HCl. solid dispersion of Pioglitazone HCl was prepared by solvent evaporation method. Solid dispersions were evaluated with respect to their yield percentage, percent drug content, FT-IR spectra and in vitro dissolution studies. The histogram response, descriptive statistics of response ensure the fitness of the experiment. The result obtained show that the dissolution profile of Pioglitazone HCl solid dispersion was considerably improved. Solid dispersions of Pioglitazone HCl with PVP K30, HPMC, PEG 6000, Eudragit EPO and Poloxamer 407 shows 75%, 74%, 100%, 50% and 62% release respectively after 30 minutes where as Pioglitazone HCl shows only 12.05%. Based on the result solid dispersion technique can be an acceptable method for improving the dissolution profile of poorly aqueous soluble drug. [ABSTRACT FROM AUTHOR]

Purpose: The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT EPO (EPO) was investigated. Methods: The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. Results: Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration- versus-time curve. Solid-state H spin-lattice relaxation time (T) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and C-T measurements. Solution-state H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. H-T and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. Conclusions: The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO. [ABSTRACT FROM AUTHOR]