Poly(pseudo)rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers.

This work aimed to develop water-based formulations for onychomycosis topical treatment using micelles of small pegylated surfactants associated with α-cyclodextrin (αCD) to deliver terbinafine to the nail. Kolliphor® RH40 (RH40) and Gelucire® 48/16 (GEL) single and mixed micelles (RH40:GEL 1:1) were prepared. αCD was added to the surfactants dispersions to form poly(pseudo)rotaxanes (PPR). Formulations were characterized in terms of drug solubilization (3 to 34-fold increase), particle size (9-11 nm) and Z-potential (+0.3 - +1.96 mV), blood compatibility (non-hemolytic), rheological behavior (solid-like viscoelastic properties after 5-10% αCD addition), drug release and interaction with the nail plate. GEL micelles and surfactant-10% αCD PPRs notably hydrated the nail plate. The high viscosity of PPR led to a slower drug release, except for RH40:GEL +10% αCD that surprisingly released terbinafine faster. The RH40:GEL +10% αCD formulation delivered twice more amount of terbinafine to deeper regions of nail plate compared to other formulations. The results evidenced the potential of PPR formed by small pegylated surfactants as a water-based formulation for nail drug delivery.

Tuning the Mechanical and Thermal Properties of Hydroxypropyl Methylcellulose Cryogels with the Aid of Surfactants.

The mechanical and thermal properties of cryogels depend on their microstructure. In this study, the microstructure of hydroxypropyl methylcellulose (HPMC) cryogels was modified by the addition of ionic (bis (2-ethylhexyl) sodium sulfosuccinate, AOT) and non-ionic (Kolliphor® EL) surfactants to the precursor hydrogels (30 g/L). The surfactant concentrations varied from 0.2 mmol/L to 3.0 mmol/L. All of the hydrogels presented viscous behavior (G″ > G'). Hydrogels containing AOT (c > 2.0 mmol/L) led to cryogels with the lowest compressive modulus (13 ± 1 kPa), the highest specific surface area (2.31 m2/g), the lowest thermal conductivity (0.030 W/(m·°C)), and less hygroscopic walls. The addition of Kolliphor® EL to the hydrogels yielded the stiffest cryogels (320 ± 32 kPa) with the lowest specific surface area (1.11 m2/g) and the highest thermal conductivity (0.055 W/(m·°C)). Density functional theory (DFT) calculations indicated an interaction energy of -31.8 kcal/mol due to the interaction between the AOT sulfonate group and the HPMC hydroxyl group and the hydrogen bond between the AOT carbonyl group and the HPMC hydroxyl group. The interaction energy between the HPMC hydroxyl group and the Kolliphor® EL hydroxyl group was calculated as -7.91 kcal/mol. A model was proposed to describe the effects of AOT or Kolliphor® EL on the microstructures and the mechanical/thermal properties of HPMC cryogels.

Liquisolid pellets: A pharmaceutical technology strategy to improve the dissolution rate of ritonavir.

Liquisolid pellets (LPs) prepared by extrusion-spheronization are promising delivery systems to improve the dissolution rate of poorly water-soluble drugs. However, developing LPs for high dose drugs (e.g. antiretroviral ritonavir, RTV) is a major challenge due to technical and quality constraints. In this study, formulations LP1 and LP2 were obtained (RTV 100 mg/unit dose) using microcrystalline cellulose (carrier), Kollidon® CL-SF (coating and disintegrating material) and high load (30%, w/w) of Kolliphor® EL or PEG 400 (non-volatile solvent). LP1 and LP2 had narrow size distribution, good morphological properties, and excellent flowability. The partial conversion of RTV polymorph I to the less soluble form II occurred during the preparation of the liquid medications. LP1 (containing Kolliphor® EL) achieved 82.64 ±â€¯2.17% of drug dissolved in 30 min (Q30min), compared with 53.14 ±â€¯0.6% and 42.42 ±â€¯2.09% for LP2 (containing PEG 400) and Norvir® tablets, respectively. Also, LP1 promoted 1.9-fold/1.7-fold and 8.19-fold/8.29-fold increases in Q30min/DE60min (dissolution efficiency) as compared to neat RTV polymorphs I and II, respectively.

Nanoemulsions Loaded with Amphotericin B: Development, Characterization and Leishmanicidal Activity.

Leishmaniasis is one of the most neglected diseases in the world. Its most severe clinical form, called visceral, if left untreated, can be fatal. Conventional therapy is based on the use of pentavalent antimonials and includes amphotericin B (AmB) as a second-choice drug. The micellar formulation of AmB, although effective, is associated with acute and chronic toxicity. Commercially-available lipid formulations emerged to overcome such drawbacks, but their high cost limits their widespread use. Drug delivery systems such as nanoemulsions (NE) have proven ability to solubilize hydrophobic compounds, improve absorption and bioavailability, increase efficacy and reduce toxicity of encapsulated drugs. NE become even more attractive because they are inexpensive and easy to prepare. The aim of this work was to incorporate AmB in NE prepared by sonicating a mixture of surfactants, Kolliphor® HS15 (KHS15) and Brij® 52, and an oil, isopropyl myristate. NE exhibited neutral pH, conductivity values consistent with oil in water systems, spherical structures with negative Zeta potential value, monomodal size distribution and average diameter of drug-containing droplets ranging from 33 to 132 nm. AmB did not modify the thermal behavior of the system, likely due to its dispersion in the internal phase. Statistically similar antileishmanial activity of AmB-loaded NE to that of AmB micellar formulation suggests further exploring them in terms of toxicity and effectiveness against amastigotes, with the aim of offering an alternative to treat visceral leishmaniasis.

Physical and chemical stability under environmental stress of microemulsions formulated with fish oil.

Enrichment of food and beverages with bioactive lipids is an important initiative to improve consumer's health. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids present in fish oil have been reported as those with the greatest bioactivity. Emulsions are an interesting alternative to incorporate functional oil; however, there are few studies on food microemulsions as a way to include this kind of compounds. The present work is intended to deepen the analysis of the Kolliphor RH40 emulsifier with potential application in food microemulsions, characterizing its micellar size and thermo-rheological properties, as well as analyzing the effect of environmental stress on physical and oxidative stability of a microemulsion containing fish oil. No significant changes in droplets size (<15 nm) or in their distribution was observed in a wide range of pH (3-9), ionic strength (0.1-10% CaCl2), centrifuging and different thermal treatments. During freezing, a slight increase in size (<21 nm) was detected, maintaining its optically transparent appearance. The high surface area of the microemulsion droplets led to the decrease in oxidative stability compared to fish oil in bulk. However, when microemulsions were stored at 4 °C, the EPA and DHA contents did not change during storage for 60 days.