David Quintanar-Guerrero

Preparation and characterization of nanocapsules from preformed polymers by a new process based on emulsification-diffusion technique.

AbstractPurpose. The aim of this study was to investigate whether biodegradable nanocapsules could be obtained by the emulsification-diffusion technique. Methods. This technique consists of emulsifying an organic solution containing an oil, a polymer, and a drug in an aqueous solution of a stabilizing agent. The subsequent addition of water to the system induces solvent diffusion into the external phase, resulting in the formation of colloidal particles. Nanoparticles obtained in this way were characterized by their particle size, zeta potential, isopycnic density and drug entrapment. The shape, surface and structure of the nanocapsules were evaluated by freeze fracture scanning electron microscopy (SEM) and by atomic force microscopy (AFM). Results. Density gradient centrifugation confirmed the formation of nanocapsules. The density was found to be intermediate between those of nanoemulsions and nanospheres. The existence of a unique density band indicated high yields. Nanocapsule density was a function of the original oil/polymer ratio, revealing that the polymer content and, consequently, the wall thickness, can be controlled by this method. SEM and AFM showed the presence of capsular structures with smooth homogeneous walls. The versatility and effectiveness of the method were demonstrated using different lipophilic drug/oil core/wall polymer/partially water-miscible solvent systems. The mechanism of nanocapsule formation was explained as a chemical instability (diffusion stranding) generated during diffusion. Conclusions. This study demonstrated that the emulsification-diffusion technique enables the preparation of nanocapsules in a simple, efficient, reproducible and versatile manner.

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

Applications of the Ion-Pair Concept to Hydrophilic Substances with Special Emphasis on Peptides

Previous investigations have shown that ionic drugs with high aqueous solubilities can be lipophilized by ion-pair formation, with appropriate counter-ions. This type of association may prove promising for several biopharmaceutical, analytical and technological applications. This review examines the ion-pair concept with special emphasis on its application to peptides. The conditions for ion-pair formation of different molecules, as well as their transfer to organic solvents, are described. The use of ion-pairs to increase the permeation of various therapeutic agents, including peptidic drugs, is also discussed. Recent uses of ion-pairs in micro- and nanoencapsulation of peptides are also commented upon.

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 vitro evaluation of the bioadhesive properties of hydrophobic polybasic gels containing N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate.

The bioadhesive properties of the hydrophobic, basic polyelectrolyte hydrogel disks containing crosslinked N,N-dimethylaminoethyl methacrylate-co-methyl methacrylate 30/70mol% were evaluated in vitro using gastric (pH 1.2), sublingual (pH 6.5), vaginal (pH 4.0) and intestinal (pH 7.5) pigs mucosas. Adhesive strength was measured using a modified Du Noüy tensiometer by measuring the force of detachment between a gel disk and the respective mucosa. The effect of crosslinker content in the gel was evaluated. It was found an increase in the adhesive strength with the increase of crosslinker content in the pH range of 4.0-7.5. For the evaluation at pH 1.2 (gastric mucosa) the opposite behavior was observed. The results indicate that initial bioadhesive contact may be the result of surface energy effects and/or electrostatic interactions of oppositely charged groups between mucin and the gel. In some cases, mucus dehydration may also be involved. When the gel is swollen, chain interpenetration also plays a roll in the bioadhesive interaction. The gels presented bioadhesive forces in gastric and vaginal mucosas (acidic medium), similar to the adhesive forces of well-known bioadhesives such as hydroxymethylcellulose and sodium alginate to the intestinal mucosa. The results indicate that hydrophobic polybasic gels present bioadhesive properties that make them suitable for site specific, pH controlled drug delivery.