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The aim of this work was to develop self-microemulsifying lipid-based formulations of trans-resveratrol in cod liver oil, a long chain lipid, to increase its solubility, dissolution rate and oral bioavailability. Ternary phase diagrams of cod liver oil with surfactant and water as well as pseudo-ternary phase diagrams of the same by mixing cod liver oil (triglyceride) with glycerol monooleate (monoglyeride) were constructed to identify regions where microemulsions were formed. Kolliphor RH 40, Tween 80 and their 1:1-mixtures were evaluated as surfactants. No organic cosolvents were added. It was observed that cod liver oil alone did not form microemulsion with any of the surfactants used, and a 1:1 mixture of cod liver oil and glycerol monooleate was necessary to enable the formation of microemulsion. Among the surfactants, Kolliphor RH 40 provided the maximum microemulsification effect. Several formulations containing 6:4, 1:1, and 4:6 w/w ratios of lipid to surfactant using the 1:1 mixture of cod liver oil and glycerol monooleate as lipid components and Kolliphor RH 40 or its mixture with Tween 80 as surfactants were identified, and trans-resveratrol solubility in these formulations were determined. Drug concentrations used in the formulations were 80% of saturation solubility, and no organic cosolvents were used in any formulations to increase drug solubility or enable emulsification. In vitro dispersion testing in 250 mL of 0.01 N HCl (pH 2) according to the USP method 2 at 50 RPM showed that the formulations rapidly dispersed in aqueous media forming microemulsions and there was no drug precipitation. [ABSTRACT FROM AUTHOR]

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 oilebased 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 β-cyclodextrin (βCD), methyl-βCD, 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 drugcomponent 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% βCD 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. [ABSTRACT FROM AUTHOR]

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]

The Imiquimod (IMQ) formulation for cutaneous administration is challenging due to its very low solubility and its poor penetration properties. The purpose of this study was to develop medium or high fluidity microemulsions (ME) to increase the solubility and modulate the release for the topical administration of Imiquimod (IMQ), thus increasing the therapeutic efficacy of the drug. Ginger oil was selected as the oil phase, Polysorbate 80/Triton X-100 1:1 as the surfactant system, and water as the aqueous phase. From the construction of a pseudo-ternary phase diagram, it was possible to obtain ME in a wide range of combinations with medium to high density. Five ME were subjected to conductivity, drug incorporation, and in vitro release assays. From conductivity determinations, it was established that ME exhibited a characteristic profile of percolative conductivity, suggesting a phase inversion of W/O to direct micelles O/W. The release assay demonstrated the ability of the ME to deliver IMQ, where the ME 1–3 had a high rate of release as a function of time, and the ME 4–5 , released the drug in a sustained manner. These results indicate that the ME studied may be a promising vehicle for increasing the effectiveness of IMQ in topical dosage forms. [Display omitted] • Fluid and semisolid transparent formulations were found by PTPD. • The maximum apparent solubilities (Sapp) for IMQ observed was 59 × 101 mg/g. • The average droplet size was lower than 20 nm. • An important increase in the released IMQ was observed from F1 and F2 after 4 h. [ABSTRACT FROM AUTHOR]

• Transparent and fluid systems were obtained from 1:9 and 2:8O:S mixtures. • The size of the ACV-load formulations were in the range 108.8–344.3 nm. • The ACV apparent solubilities in ME 1-5 were 42; 51; 57.9; 78.3 and 82 mg/ml. • Polar groups play an important role in the microstructure of ME. • ACV in ME 2-5 presented Fa% higher than 90%. The purpose of this study was to improve the permeability of acyclovir (ACV) by developing a water-in-oil microemulsion, since it is an important factor that influences the oral absorption and, consequently, the oral bioavailability of drugs. Pseudoternary phase diagrams (PTPD) were constructed to identify the regions for obtaining microemulsions (ME). From the region of fluid transparent systems, five ME were chosen to evaluate the effect on ACV permeability by using two-compartment horizontal Franz diffusion cells, using a bio-mimetic artificial membrane, which simulates the typical lipophilic characteristics of the biological membranes. The characterization of ME was carried out by PTPD, conductivity determination and Nuclear Magnetic Resonance studies. The formulation that showed the higher incorporation of ACV (81.57 mg/ml) consisted of 13.3% Polysorbate 80, 13.3% ethanol, 6.6% ginger oil and 66% water. An increase in ACV permeability was observed, reaching an apparent permeability coefficient of 1.99.10−6 cm/s, corresponding to a fraction of human absorbed dose of 99.97%, according to the correlation previously established by our research group. These results indicated the ability of ME to improve the permeability of ACV, representing a system with the potential to improve the efficacy of ACV in oral administrated pharmaceutical formulation. [ABSTRACT FROM AUTHOR]