Cyclodextrin and Meglumine-Based Microemulsions as a Poorly Water-Soluble Drug Delivery System.

Cyclodextrins (CDs) and meglumine (MEG) are pharmaceutical excipients widely used to improve solubility of poorly water-soluble drugs. The purpose of this work was to study the effect of CDs or MEG on the internal microstructure of soya oil-based O/W microemulsions (MEs) and on the modulation of the solubility and release rate of Class II model hydrophobic drugs, sulfamerazine and indomethacin. The pseudoternary phase diagrams revealed that higher proportions of oil phase, as well as the presence of ß-cyclodextrin (ßCD), methyl-ßCD, and MEG, favored the incorporation of the drugs. The conductivity studies, particle size, and zeta potential analysis showed that the O/W ME structure remained unaffected and that the ME presented reduced droplet sizes after the incorporation of the ligands. The drug-component interactions were assessed by proton nuclear magnetic resonance studies. The highest incorporations of sulfamerazine (35.6 mg/mL) and indomethacin (73.1 mg/mL) were obtained with the ME with W = 5%, MEG and W = 1.8% ßCD in a phosphate buffer solution of pH 8, respectively. In addition, the ligands in ME significantly enhanced the released amount of the drugs, probably due to a solubilizing effect that facilitates the drug to penetrate the unstirred water layer adjacent to membranes.

Development and Characterization of a Biocompatible Soybean Oil-Based Microemulsion for the Delivery of Poorly Water-Soluble Drugs.

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.

Chitosan membranes modified by contact with poly(acrylic acid).

In this work chitosan membranes modified by contact with poly(acrylic acid) (PAA) aqueous solution at two different temperatures (25 degrees C and 60 degrees C) were obtained. The pure chitosan (CS) membranes, as well as those treated with PAA (CSPAA_25 and CSPAA_60) were characterized by FTIR-ATR, water sorption capacity, thermal analysis (TG/DTG), and scanning electron microscopy (SEM). In addition, in vitro permeation experiments were carried out using metronidazol and sodium sulfamerazine aqueous solutions at 0.1% and 0.2% as model drugs. FTIR-ATR results showed the presence of absorption bands of NH3+ and COO(-) indicating the formation of a polyelectrolyte complex between chitosan and poly(acrylic acid). The results also indicated that PAA penetrates deeper into the membrane at higher temperature (60 degrees C), forming a thicker complex layer. Polyelectrolyte complex formation as well as the influence of treatment temperature was confirmed by lower hydrophilicity, higher thermal stability, and lower permeability of the treated membranes. The results show that the methodology used is a simple and very efficient way to drastically change some membrane properties, especially their permeability.