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Penetration Enhancers (penetration + enhancer)
Selected AbstractsEffects of (,)-carveol and HPMC on the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide formulations in normotensive New Zealand rabbitsDRUG DEVELOPMENT RESEARCH, Issue 3 2009Mohsen I. Afouna Abstract The objective of the current study was to maximize the ocular bioavailability of the carbonic anhydrase inhibitor, dorzolamide hydrochloride (DZD) via (a) enhancement of DZD corneal transport using terpene enhancers, (b) reducing pre-corneal loss of the installed dose via increased formulation viscosity, and (c) assessment of the in vivo intraocular pressure (IOP) lowering effects of test formulations using rabbit. DZD was formulated as a 2% ophthalmic solution containing different concentrations of HPMC as a viscosity improving agent (VIA), and (,)-carveol as a corneal penetration enhancer. The transport of DZD from test formulations was quantitatively determined using in vitro diffusion experiments, the permeability parameters were mathematically calculated, and the in vivo IOP lowering effects were assessed using a Tono-Pen XL® tonometer. The results revealed a good correlation between the in vitro permeability parameters and the in vivo ,IOP. The magnitude of the DZD-IOP lowering effects and durations of actions for DZD formulations were dependent on (a) the concentration of (,)-carveol, and (b) the contact period with ocular tissue which was found to be a single-valued function of the HPMC as VIA. Drug Dev Res 70, 2009. © 2009 Wiley-Liss, Inc. [source] Evaluation of buccal methyl-,-cyclodextrin toxicity on human oral epithelial cell culture modelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2005Laïla Boulmedarat Abstract Cyclodextrins, especially methylated ,-cyclodextrins offer several advantages for drug delivery which include improved drug solubilization, protection against physicochemical and enzymatic degradation, as well as a potential for absorption improvement. However, little or no data are available for their use as drug penetration enhancer via the buccal route. This study focuses on the toxicity of randomly methylated ,-cyclodextrin (RAMEB) on buccal mucosa using a reconstituted human oral epithelium model composed of TR 146 cells. Toxicity of RAMEB on TR 146 cells was evaluated by measuring cell viability (MTT assay) and membrane damages followed by LDH release after single and repeated exposures to RAMEB solutions. Inflammatory effects of RAMEB are also considered by measuring expression of interleukin-1, and are supported by histological examination. The present results indicate that 10% RAMEB results in cytotoxic and inflammatory effects depending on time exposure, whereas 2% and 5% RAMEB do not induce tissue damages even after 5 days of repeated exposures. Therefore, the highly water-soluble RAMEB is thought to be a safe candidate as an excipient for buccal mucosal drug delivery. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1300,1309, 2005 [source] Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunumJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Giuseppina Sandri The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir. [source] Skin disposition of menthol after its application in the presence of drug substancesBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 8 2008Krzysztof Cal Abstract Many drug products that are applied onto the skin contain menthol. Menthol plays a dual role in the analgesic and anti-inflammatory drugs: it causes cooling and local anesthetic effects and, being a penetration enhancer, it increases the skin permeation of the drug substances. However, there are no data concerning the skin penetration of menthol after its application in the most commonly used vehicles and in the presence of drug substances. Therefore, this study evaluated the ex vivo skin disposition of menthol after application of the commercially available drug products containing aluminum acetotartrate, methyl salicylate, ibuprofen and naproxen, using full human-skin mounted in flow-through diffusion cells. After 15, 30 and 60,min of application, the skin was progressively tape-stripped into three fractions of stratum corneum and the remaining epidermis with dermis. The content of menthol in the skin layers was determined by GC method. Varying degrees of penetration of menthol into the skin layers was observed, depending on its amount in the vehicle and the presence of drug substance. In the presence of aluminum acetotartrate, the skin penetration of menthol was limited only to the outer fraction of the stratum corneum. In the case of drug products containing naproxen, the concentration of the drug substance significantly influenced the skin penetration of menthol. Copyright © 2008 John Wiley & Sons, Ltd. [source] Design of improved permeation enhancers for transdermal drug deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2009Srinivas S. Godavarthy Abstract One promising way to breach the skin's natural barrier to drugs is by the application of chemicals called penetration enhancers. However, identifying potential enhancers is difficult and time consuming. We have developed a virtual screening algorithm for generating potential chemical penetration enhancers (CPEs) by integrating nonlinear, theory-based quantitative structure,property relationship models, genetic algorithms, and neural networks. Our newly developed algorithm was used to identify seven potential CPE molecular structures. These chemical enhancers were tested for their toxicity on (a) mouse embryonic fibroblasts (MEFs) with MTT assay, and (b) porcine abdominal skin by histology using H/E staining at the end of a 48-h exposure period to the chemicals. Further, melatonin permeability in the presence of the enhancers was tested using porcine skin and Franz diffusion cells. Careful toxicity tests showed that four of the seven "general" CPEs were nontoxic candidate enhancers (menthone, 1-(1-adamantyl)-2-pyrrolidinone, R(+)-3-amino-1-hydroxy-2-pyrrolidinone, and 1-(4-nitro-phenyl)-pyrrolidine-2,5-dione). Further testing of these four molecules as potential melatonin-specific CPEs revealed that only menthone and 1-dodecyl-2-pyrrolidinone provided sufficient enhancement of the melatonin permeation. The results from our permeability and toxicity measurements provide validation of the efficacy and ability of our virtual screening algorithm for generating potential chemical enhancer structures by virtual screening algorithms, in addition to providing additional experimental data to the body of knowledge. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4085,4099, 2009 [source] Effect of lipid bilayer alteration on transdermal delivery of a high-molecular-weight and lipophilic drug: Studies with paclitaxelJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2004Ramesh Panchagnula Abstract Skin forms an excellent barrier against drug permeation, due to the rigid lamellar structure of the stratum corneum (SC) lipids. Poor permeability of drugs can be enhanced through alteration in partition and diffusion coefficients, or concentration gradient of drug with an appropriate choice of solvent system, along with penetration enhancers. The aim of the current investigation was to assess applicability of lipid bilayer alteration by fatty acids and terpenes toward the permeation enhancement of a high-molecular-weight, lipophilic drug, paclitaxel (PCL) through rat skin. From among the fatty acids studied using ethanol/isopropyl myristate (1:1) vehicle, no significant enhancement in flux of PCL was observed (p,>,0.05). In the case of cis mono and polyunsaturated fatty acids lag time was found to be similar to control (p,>,0.05). This suggests that the permeation of a high-molecular-weight, lipophilic drug may not be enhanced by the alteration of the lipid bilayer, or the main barrier to permeation could lie in lower hydrophilic layers of skin. A significant increase in lag time was observed with trans unsaturated fatty acids unlike the cis isomers, and this was explained on the basis of conformation and preferential partitioning of fatty acids into skin. From among the terpenes, flux of PCL with cineole was significantly different from other studied terpenes and controls, and after treatment with menthol and menthone permeability was found to be reduced. Menthol and menthone cause loosening of the SC lipid bilayer due to breaking of hydrogen bonding between ceramides, resulting in penetration of water into the lipids of the SC lipid bilayer that leads to creation of new aqueous channels and is responsible for increased hydrophilicity of SC. This increased hydrophilicity of the SC bilayer might have resulted in unfavorable conditions for ethanol/isopropyl myristate (1:1) along with PCL to penetrate into skin, therefore permeability was reduced. The findings of this study suggest that the permeation of a high-molecular-weight and lipophilic drug cannot be enhanced through bilayer alteration by penetration enhancers, and alteration in partitioning of drug into skin could be a feasible mode to enhance the permeation of drug. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:2177,2183, 2004 [source] Investigation of nail permeation enhancement by chemical modification using water as a probeJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2002Gouri G. Malhotra Abstract Our objective was to screen molecules that could interact with keratin in the human nail and thereby improve the topical penetration of actives into and through the nail plate. We used specialized Franz-type diffusion cells for our permeation experiments and water as a marker molecule. Aqueous/hydroalcoholic gels containing the enhancers were spiked with tritiated water and compared with a control (without enhancer). We computed the normalized water flux (defined as a product of flux and nail thickness) for each gel. We defined an enhancement factor for water as the ratio of the normalized water flux from a gel containing enhancer to that of the control. Our results indicate that the chemical structure of the modifier is most important in determining its ability to enhance penetration. The best enhancement effect was obtained using N-(2-mercaptopropionyl) glycine, a mercaptan derivative of an amino acid, in combination with urea. The concentration of each chemical modifier was linearly related to normalized water flux and mercaptan levels were more important that urea levels in penetration enhancement. Barrier integrity of nails was compromised after treatment with effective chemical modifiers. Thus, we have developed a suitable technique to screen nail penetration enhancers using water as a probe. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:312,323, 2002 [source] Liposomes in dermatology todayJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2009J De Leeuw Abstract Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT). Conflicts of interest None declared [source] Incorporation of ceramide 3B in dermatocosmetic emulsions: effect on the transepidermal water loss of sodium lauryl sulphate-damaged skinJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2000Kristien De Paepe Abstract Background In previous work we reported on the efficacy of cosmetic body lotions enriched with skin-identical lipids to reduce the transepidermal water loss (TEWL) of ageing and sodium lauryl sulphate (SLS)-damaged skin. The observations made depended on the experimental design and clearly raised the question of the importance of the galenic formulation of skin ceramide-containing products. Objectives The aim of the present work was to study the different galenic forms in which ceramide 3B (0.2% w/v) can be incorporated into common o/w emulsions. In addition, we investigated whether supplementation of skin care products with ceramide 3B enriched with penetration enhancers and coemulsifiers could exert a beneficial effect on barrier function, done by measuring their effects on the TEWL of SLS-induced scaly skin. Results We found that the technique of incorporating ceramide 3B into the o/w emulsions was important for their final stability. However, no additional positive effect on the TEWL values of SLS-damaged skin could be observed when the efficacy of the ceramide-containing emulsions was compared with that of proper controls. Conclusions Although suitable galenic formulas were developed, no positive effect on TEWL could be observed when ceramide 3B was added in a final concentration of 0.2% (w/v) to different o/w emulsions and applied to SLS-damaged skin. [source] Pharmaceutical and therapeutic Potentials of essential oils and their individual volatile constituents: a reviewPHYTOTHERAPY RESEARCH, Issue 4 2007Amr E. Edris Abstract Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible role and mode of action of these natural products is discussed with regard to the prevention and treatment of cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy will also be outlined. Copyright © 2007 John Wiley & Sons, Ltd. [source] Transdermal delivery system for zidovudine: in vitro, ex vivo and in vivo evaluationBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2004Sunil Thomas Kumar Narishetty Abstract The objective of this study was to prepare a transdermal delivery system (TDS) for zidovudine (AZT) with a combination of menthol and oleic acid as penetration enhancers incorporated in hydroxypropyl methylcellulose, and to evaluate ex vivo as well as in vivo permeation across rat skin. It was found that AZT in gel formulation was stable in both refrigerated as well as accelerated stability conditions for 3 months and further, the gel did not significantly retard the permeability of AZT across the skin in comparison with solution formulation. Ex vivo steady state flux of AZT across rat skin from gel was 2.26 mg cm,2 h,1, which is sufficient to achieve therapeutic plasma concentrations. Intravenous pharmacokinetic parameters of AZT in rats were determined and used together with ex vivo flux data to generate theoretical plasma profiles of AZT and compared with plasma concentrations achieved after application of TDS. Further, steady state plasma concentrations of drug following multiple applications of TDS were determined and good correlations between ex vivo and in vivo data were observed. In addition, the combination of penetration enhancers used at 2.5% w/w in this study proved efficient in achieving sufficient enhancement in the transdermal permeability of AZT across rat skin with reduced skin irritation potential when compared with individual penetration enhancers at higher concentrations. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||