Adriana Ganem-Quintanar

Monoolein: a review of the pharmaceutical applications

Although monoolein is a well-known molecule commonly used as an emulsifying agent and as a food additive since the 1950s, its potential applicability in the pharmaceutical industry has not been considered in great detail. Recently, there has been a flurry of activity concerned with the possibility of using monoolein as a material for different pharmaceutical applications. The explosion of interest in this field is evidenced by an increase in the number of publications in the area (1). Figure 1 shows the percentage of consulted references of monoolein versus publication year. It is important to point out that only articles falling in the pharmaceutical area were considered when creating this graphic. Between 1978 and 1987, monoolein was used mainly as an absorption enhancer in combination with bile salts and as an emulsifier. It was in 1984 that monoolein was first

The Tape-Stripping Technique as a Method for Drug Quantification in Skin

Quantification of drugs within the skin is essential for topical and transdermal delivery research. Over the last two decades, horizontal sectioning, consisting of tape stripping throughout the stratum corneum, has become one of the traditional investigative techniques. Tape stripping of human stratum corneum is widely used as a method for studying the kinetics and penetration depth of drugs. This paper shows the applications of the tape stripping technique to quantify drug penetration through the skin, underlining its versatile application in the area of topical and transdermal drugs.

Effects of sucrose oleate and sucrose laureate on in vivo human stratum corneum permeability

AbstractPurpose. The purpose of this work was to 1) investigate the effect of sucrose esters (sucrose oleate and sucrose laureate in water or in Transcutol®, TC) on the stratum corneum (SC) barrier properties in vivo and 2) examine the impact of these surfactant-like molecules on the in vivo percutaneous penetration of a model penetrant 4-hydroxybenzonitrile (4-HB). Methods. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and transepidermal water loss measurements were used to evaluate the sucrose oleate- and sucrose laureate-induced biophysical changes in SC barrier function in vivo. In addition, the effect of the enhancers on 4-HB penetration was monitored in vivo using ATR-FTIR spectroscopy in conjunction with tape-stripping of the treated site. Results. Treatment of the skin with 2% sucrose laureate or sucrose oleate in TC significantly increased the extent of 4-HB penetration relative to the control. Furthermore, when skin treated with these formulations was examined spectroscopically, the C-H asymmetric and symmetric stretching bands of the lipid methylene groups were characterized by 1) decreased absorbances and 2) frequency shifts to higher wavenumbers. These effects on the SC lipids and 4-HB penetration were more pronounced for sucrose laureate when combined with TC. Conclusions. A combination of sucrose esters (oleate or laureate) and TC is able to temporally alter the stratum corneum barrier properties, thereby promoting 4-HB penetration. These molecules are worthy of further investigation as potential candidates for inclusion in transdermal formulations as penetration enhancers.

Silica xerogels as pharmaceutical drug carriers

This review focuses on silica xerogels obtained by the sol-gel method and their application as drug delivery systems. SiO2 xerogels are potential biomaterials to be used as matrix materials for the extended and controlled release of different kinds of biologically active agents administered by various routes. The article includes some representative examples that describe the encapsulation of bioactive molecules and model compounds inside a silica matrix produced by the conventional sol-gel method or by ultrasound hydrolysis. The drug release rate from xerogels could be modified by adjusting several parameters, such as the type of precursor, the concentration of the catalyst and drying temperature. In vitro and in vivo studies have shown the efficacy and biodegradability of these composites. The potential application of silica xerogels as drug carrier systems is critically analyzed and discussed.

Ex vivo oral mucosal permeation of lidocaine hydrochloride with sucrose fatty acid esters as absorption enhancers

The ex vivo permeation of lidocaine hydrochloride, a model drug, was studied in two different regions of the oral mucosa: pig palate (keratinized) and cheek (non-keratinized). The enhancing effect of a series of sucrose fatty acid esters (nonionic surfactants), which have the advantage of reduced irritation potential relative to other enhancers, was investigated. Among the sucrose esters tested, an increase in the passage of lidocaine through buccal and palatal mucosae was observed only for sucrose laurate (L-1695) (enhancement ratio (ER) ∼22 for buccal and ∼14 for palatal mucosa). The other sucrose esters (S-1670, O-1570 and P-1670), did not show any promoting effect. The type of fatty acid sucrose ester, was found to be a key factor for promoting the absorption of lidocaine. The contribution of sucrose esters was compared with that of other enhancers, such as ethanol, oleic acid and Transcutol®. A significant enhancing effect was observed with oleic acid/hydroalcoholic solution, for both buccal and palatal mucosa (ER ∼13 and ∼61, respectively). However, there was no promotion when the hydroalcoholic solution was applied in the absence of oleic acid. A synergic effect between oleic acid and ethanol is very probable. A slight promoting effect was obtained when Transcutol/water (50:50) was used as the vehicle.

The Effect of Keratolytic Agents on the Permeability of Three Imidazole Antimycotic Drugs Through the Human Nail

The permeability of three imidazole antimycotics (miconazole nitrate, ketoconazole, and itraconazole) through the free edge of healthy human nail was evaluated in vitro using side-by-side diffusion cells. The influence of keratolytic substances (papain, urea, and salicylic acid) on the permeability of the antimycotics was also studied. The results suggested that the nail constituted an impermeable barrier for these antimycotics; it could be considered that the nail behaved as a hydrophilic gel membrane, through which drugs of low solubility could not permeate. The use of ethanol did not promote the passage of any of the antimycotic drugs. Although scanning electron microscopy indicated that the keratolytic substances had a significant effect on the nail surface (papain > salicylic acid > urea), the passage of the three antimycotics was not improved by pretreatment with salicylic acid alone (20% for 10 days), or by the application of the drug in a 40% urea solution. It was found that only the combined effects of papain (15% for 1 day) and salicylic acid (20% for 10 days) were capable of enhancing the permeability of the antimycotic.

Influence of sucrose esters on the in vivo percutaneous penetration of octyl methoxycinnamate formulated in nanocapsules, nanoemulsion, and emulsion

ABSTRACT The influence of sucrose laureate and sucrose oleate on the in vivo percutaneous penetration of octyl methoxycinnamate (OMC) formulated in i) colloidal suspensions (nano-emulsions and nanocapsules), and ii) conventional o/w emulsions was evaluated. The results showed that nano-emulsions formulated with sucrose laureate exhibited the highest penetration in the stratum corneum compared to the other formulations. A two-fold increase in OMC skin deposition was observed with the nano-emulsion containing sucrose laureate when compared to the control. The data obtained suggest that the total amount of OMC detected in the stratum corneum and the penetration depth are strongly dependent upon the formulations nature, the particle size, and the type of enhancer.

In Vivo Skin Permeation of Sodium Naproxen Formulated in Pluronic F-127 Gels: Effect of Azone® and Transcutol®

The objective of this study was to determine the penetration of sodium naproxen, formulated in Pluronic F-127 (PF-127) gels containing Azone® and Transcutol® as penetration enhancers, through human skin in vivo. It was found that the combination of Azone® and Transcutol® in PF-127 gels enhanced sodium naproxen penetration, with enhancement ratios of up to two fold compared with the formulation containing only Transcutol®. These results were confirmed by TEWL and ATR-FTIR spectroscopy, suggesting a synergic action for Azone® and Transcutol®. Because of the thermo-reversible behavior of Pluronic gels, the influence of the components added to the gel formulations on viscosity, as a function of temperature, was also studied.

Evaluation of the transepidermal permeation of diethylene glycol monoethyl ether and skin water loss

The rate of Transcutol® (TC)-water interchange, was studied using whole and stripped hairless rat skin in a modified vertical Franz diffusion cell. The presence of stratum corneum limited the passage of the two solvents, but after stripping of the skin, the rate of TC transfer increased and the water flow rose until the vapour pressure at the skin surface and in the ambient air was similar. The results suggest that TC increased the donor hydration by increasing the outflow of water, with a change in the donor composition. These two opposite fluxes and the alteration of the bulk constitution of the skin and of the donor compartment throughout the experiment, are important factors to be considered for the permeation studies with this solvent.

Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles

Objective: The essential aim of this article is to prepare solid lipid nanoparticles (SLNs) by emulsification and solvent displacement method and to determine the best process conditions to obtain submicron particles. Methods: The emulsification and solvent displacement method is a modification of the well-known emulsification–diffusion method, but without dilution of the system. The extraction of the partially water-miscible solvent from the emulsion globules is carried out under reduced pressure, which causes the diffusion of the solvent toward the external phase, with subsequent lipid aggregation in particles whose size will depend on the process conditions. The critical variables affecting the process, such as stirring rate, the proportion of phases in the emulsion, and the amount of stabilizer and lipid, were evaluated and optimized. Results: By this method, it was possible to obtain a high yield of solids in the dispersion for the lipids evaluated (Compritol® ATO 888, Geleol®, Gelucire® 44/14, and stearic acid). SLNs of up to ∼20 mg/mL were obtained for all lipids evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a transition from micro- to nanometric size was observed. The smaller particle sizes obtained were 113 nm for Compritol® ATO 888, 70 nm for Gelucire® 44/14, 210 nm for Geleol®, and 527 nm for stearic acid, using a rotor–stator homogenizer (Ultra-Turrax®) at 16,000 rpm. The best phase ratio (organic/aqueous) was 1 : 2. Conclusions: The process proposed in this study is a new alternative to prepare SLNs with technological potential.