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| REVIEW ARTICLE |
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| Year : 2012 | Volume
: 4
| Issue : 1 | Page : 2-9 |
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Status of surfactants as penetration enhancers in transdermal drug delivery
Iti Som, Kashish Bhatia, Mohd. Yasir
Department of Pharmaceutics, ITS Paramedical (Pharmacy) College, Ghaziabad, Uttar Pradesh, India
| Date of Submission | 15-Mar-2011 |
| Date of Decision | 12-Apr-2011 |
| Date of Acceptance | 20-May-2011 |
| Date of Web Publication | 9-Feb-2012 |
Correspondence Address:
Mohd. Yasir
Department of Pharmaceutics, ITS Paramedical (Pharmacy) College, Ghaziabad, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0975-7406.92724
 Abstract | | |
Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs. Keywords: Penetration enhancer, surfactant, skin, sodium lauryl sulfate, Tween 80
How to cite this article:
Som I, Bhatia K, Mohd. Yasir. Status of surfactants as penetration enhancers in transdermal drug delivery. J Pharm Bioall Sci 2012;4:2-9 |
How to cite this URL:
Som I, Bhatia K, Mohd. Yasir. Status of surfactants as penetration enhancers in transdermal drug delivery. J Pharm Bioall Sci [serial online] 2012 [cited 2020 Nov 29];4:2-9. Available from: https://www.jpbsonline.org/text.asp?2012/4/1/2/92724 |
Nowadays, the transdermal route has become one of the most successful and innovative focus for research in drug delivery, with around 40% of the drug candidate being under clinical evaluation related to transdermal or dermal systems. But the barrier property of skin causes difficulties for transdermal delivery of therapeutic agents. [1] One long-standing approach to increase the range of drugs that can be effectively delivered via this route has been to use penetration enhancers, chemicals that interact with skin constituents to promote drug flux. [2] Skin penetration enhancers are molecules which reversibly remove the barrier resistance of the stratum corneum. They allow drugs to penetrate more readily to the viable tissues and thus enter the systemic circulation. [3] Usually, surfactants are added to formulations in order to solubilize lipophilic active ingredients, so they have potential to solubilize lipids within the stratum corneum. [2] Surfactants induce a concentration-dependent biphasic action with respect to alteration of skin permeability. At low concentrations, surfactants increase the permeability of the skin to many substances probably because they penetrate the skin and disrupt the skin barrier function. [4]
Surfactants are amphipathic molecules that consist of a non-polar hydrophobic portion usually a straight or branched hydrocarbon or fluorocarbon chain containing 8-18 carbon atoms, which is attached to a hydrophilic portion. The hydrophilic portion can be nonionic, ionic or zwitterion. [5] Surfactants are low to moderate molecular weight compounds which contain one hydrophobic part, which is readily soluble in oil but sparingly soluble or insoluble in water, and one hydrophilic (or polar) part, which is sparingly soluble or insoluble in oil but readily soluble in water.
| Classification of Surfactants | |  |
Surfactants are classified according to the nature of their polar head groups [6] i.e.
| Anionic Surfactants | | |
Surfactants in which the hydrophilic part carries a negative charge [Figure 1]. Examples of anionic surfactants include the following:
- Carboxylates: Alkyl carboxylates-fatty acid salts (''soaps''); carboxylate fluoro surfactants.
- Sulfates: Alkyl sulfates (RCOO) (e.g.,sodium lauryl sulfate); alkyl ether sulfates (e.g.,sodium laureth sulfate).
- Sulfonates: Docusates (e.g.,dioctyl sodium sulfosuccinate); alkyl benzene sulfonates.
- Phosphate esters: Alkyl aryl ether phosphates; alkyl ether phosphates
| Nonionic Surfactants | | |
Surfactants that do not ionize in aqueous solution, because their hydrophilic group is of a non-dissociable type, such as alcohol, phenol, ether, ester, or amide [Figure 1]. A large proportion of these nonionic surfactants are made hydrophilic by the presence of a polyethylene glycol chain, obtained by the polycondensation of ethylene oxide. Non ionic surfactants, i.e., surfactants with an uncharged polar head group, are probably the ones used most frequently in drug delivery applications. The critical micellization concentration for such surfactants is generally much lower than that of the corresponding charged surfactants, and partly due to this, such surfactants are generally less irritant and better tolerated than the anionic and cationic surfactants, e.g., polyoxyethylenes, poloxamer (188,407,338,184), poloxamine (304,904,908), polysorbates.
| Cationic Surfactants | | |
Cationic surfactants are dissociated in water into an amphiphilic cation and an anion, most often of the halogen type [Figure 1]. A very large proportion of this class corresponds to nitrogen compounds such as fatty amine salts and quaternary ammoniums, with one or several long chain of the alkyl type, often coming from natural fatty acids.
| Zwitterionic Surfactants | | |
Zwitterionic surfactants are less common than anionic, cationic and non ionic ones. When a single surfactant molecule exhibits both anionic and cationic dissociations it is called amphoteric or zwitterionic. The polar head group consists of a quaternary amine group and a sulfonic or carboxyl group [Figure 1]. This is the case of synthetic products like betaines or sulfobetaines and natural substances such as aminoacids and phospholipids (phosphatidylcholine, sphosphatidylethanolamine).
| Surfactant-Skin Interaction | | |
Many of the properties of surfactants can be related to their ability to concentrate at phase interfaces, leading to a reduction in interfacial tension. In biological systems the effect of surfactants are complex; particularly their effect on cell and other membranes, and this can lead to alterations in permeability characteristics. [7] The ability of surfactants to adsorb at interfaces and bind through hydrophobic or polar interactions may lead to desirable or undesirable effects on the skin depending on the surfactant concentration, the type of exposure, the duration of contact, and the individual response. The undesirable effects of surfactants on skin have been and are still extensively studied in vivo, by using human volunteers, and with in vitro screening tests, to predict the clinical effects of an individual surfactant as well as formulations. [8] The selection of a surfactant as a penetration enhancer should be based not only on its efficacy in enhancing skin permeation but also on its dermal toxicity (low) and its physicochemical and biological compatibility with the system's other components. [9]
Interaction of surfactants upon contact with skin:
- By binding to the surface proteins of the skin
- By denaturing skin surface proteins
- By solubilizing or disorganizing the intercellular lipids of the skin
- By penetrating through the epidermal lipid barrier
- By interacting with living cell. [10]
Interaction with skin proteins
For the surfactant molecules to interact with the deeper protein - rich regions in a normal corneum, they must diffuse through the lipid region. [11] After binding to the proteins, surfactant causes the protein to denature, leading to the swelling of stratum corneum. [10] Solubilization of fluid lipids and abstraction of calcium or other multivalent ions to reduce corneocyte adhesion enhances the accessibility of the proteins in the lower regions of the stratum corneum. [11] Rhein et.al. investigated swelling of isolated stratum corneum when exposed to various single surfactant solutions and showed that the swelling was concentration and time dependent up to the CMC before leveling off. [12] Ionic interactions between the anionic head groups and the cationic sites of the proteins are a basic requirement to induce strong hydrophobic interactions between surfactant molecule and the protein; interactions will ultimately lead to protein denaturation. [8] Anionic surfactants have ability to solubilize the less soluble proteins such as zein, or can themselves remain on the skin due to formation of chemical compounds with skin keratin. Anionic promote the dissolution of the proteins out of the skin, cause release of sulfhydryl groups from the sclera proteins, react upon various enzymes of skin and finally denaturize. Nonionic surfactant binds to proteins via weak hydrophobic interaction. [13]
Interaction with the intercellular skin lipids
The protective lipid barrier of skin is composed of highly organized lipid layers located between the cells of stratum corneum. Surfactants have to integrate into lipid bilayers to disorganize them and alter skin barrier function. Monomers of surfactant can easily reach the intercellular lipids making the effect dependent on the relative proportion of monomer in solution. [8] Fulmer et.al. studied significant changes in stratum corneum lipid composition caused by sodium dodecyl sulfate [Figure 2]. The free cholesterol to cholesterol ratio was found to be increased while the quantity of total sterols remained constant. The distribution of certain ceramide species was also found to be altered. [14] Low concentrations of surfactant may emulsify stratum corneum lipids and improve permeability; however higher concentrations promote the formation of micelles in the vehicle that trap the permeant and decrease permeability. [15] It was found that SLS [Figure 2] enhances penetration into the skin by increasing the fluidity of epidermal lipids. The increase in lipid fluidity below the applied site may allow sodium lauryl sulfate to diffuse in all directions including the radial path. [16]
Interaction with living cells
Once the lipid barrier of skin has been disrupted/ weakened, monomers of surfactant can reach the living part of the epidermis and interact with keratinocytes and langerhans cells. [8] It was found that short-term treatment of skin with sodium lauryl sulfate (0.5% v/v) disorganized the stratum corneum, induced maturation of langerhans cells, and did not result in epidermis thickening. [17]
Factors governing the activity of surfactant as a penetration enhancer
The effect of surfactant in altering the skin barrier depends on the surfactant structure; both the hydrophobic alkyl chain and the hydrophilic ethylene oxide chain demonstrate some structure-activity behavior. [18] In a study Walters et al. reported that surfactants having a linear alkyl chain greater than C8 and an ethylene oxide chain length of less than E14 caused significant increase in the flux of methyl nicotinate while those having branched or aromatic moieties in the hydrophobic portion were ineffective. [19] In another study it was found that dimethyldialkylammoniums (double chained) with relatively shorter alkyl chains, which form either vesicles with looser molecular packing or micelles and appear to be present as surfactant monomer in higher ratios than those with longer alkyl chains, favor the interaction with skin. [20] In many biological systems, including skin, surfactants with a similar hydrophilic group will show maximum membrane activity if they possess a decyl or dodecyl alkyl chain. Park et.al. reported that the enhancers containing the ethylene oxide chain length of 2-5, HLB value of 7-9 and an alkyl chain length of C16 -C18 were effective promoters of ibuprofen flux. [21] In a study the parabolic relation between the piroxicam absorption and the polyoxyethylene length of non ionic surfactant was observed.Polyoxyethylene length from 5 to 15 was found to enhance percutaneous absorption to a greater extent. [22] Dalvi and Zatz examined the influence of polyoxyethylene chain (POE) length of polyoxyethylenenonphenyl ether on penetration of benzocaine through hairless mouse skin from the aqueous solution system and found that the maximum flux was obtained by POE(9) followed by POE(12), POE(30), POE(50). [12]
Sorbitan monooleate (HLB 4.3) and polyoxyethylene n-lauryl ether (HLB 12.8) were found to interact with the human epidermis in degrees which were dependent on the polarity of the surfactant. [23] Kushla et.al. studied penetration of lidocaine through human epidermis by incorporating cationic surfactants of varying alkyl chain length from three classes:alkyl dimethylbenzyl ammonium halides, alkyl trimethyl ammonium halides, and alkyl pyridinium halides. Peak surfactant enhancement effects were seen at alkyl chain lengths of 12 or 14 carbons. [24] The nature of the enhancer head group also greatly influences cutaneous barrier impairment. Tween 20 (log Poct=3.72) which is more hydrophilic than Span20 (log Poct = 4.26) was found to be less effective in enhancing 5-fluorouracil skin penetration. Lipophilic molecules diffuse through the stratum corneum by solubilizing in the continuous intercellular lipid phase of the stratum corneum (lipophilic pathway). Span20 was found to affect the intercellular lipids by making them more fluid and enhancing the diffusivity. [25] SLS was found to remove detectable levels of lipids only above its critical micelle concentration (CMC). At high concentrations the surfactants removed only very small amounts of cholesterol, free fatty acid, the esters of those materials, and possibly squalene. Below the CMC, sodium lauryl sulfate bound and irritates the stratum corneum. [26]
| Mechanism of Action | | |
Ionic surfactant
Ionic surfactant molecules in particular tend to interact well with keratin in the corneocytes, open up the dense keratin structure and make it more permeable. [27] They are also thought to enhance transdermal absorption by disordering the lipid layer of stratum corneum. [28]
Anionic surfactants
Anionic surfactants interact strongly with both keratin and lipids. [29] It has been reported that anionic surfactants like sodium lauryl sulfate can penetrate and interact with the skin, producing large alterations in the barrier properties. [30] An additional mechanism for the penetration enhancement by SLS involves the hydrophobic interaction of the SLS alkyl chain with the skin structure which leaves the end sulfate group of the surfactant exposed, creating additional sites in the membrane. This results in the development of repulsive forces that separate the protein matrix, uncoil the filaments, and expose more water binding sites, hence increasing the hydration level of skin. [12]
Anionic materials tend to permeate relatively poorly through stratum corneum upon short-time exposure but permeation increases with application time. [2] The alkyl sulfates can penetrate and destroy the integrity of the stratum corneum within hours of application. [18] Anionic surfactants cause greater enhancement and damage than non ionic surfactants. Anionic has been found to increase deuterated water permeability of human epidermis in vitro. The surfactants such as sodium lauryl sulfate, after extended treatment, irreversibly caused protein denaturation, membrane expansion, hole formation, and the loss of water -binding capacity. [31] [Table 1] depicts the use of various anionic surfactants as enhancers in transdermal drug delivery. | Table 1: Application of anionic surfactants as penetration enhancer in transdermal drug delivery
Click here to view |
Cationic surfactants
Molecules show main action on keratin fibrils of the cornified cells and result in a disrupted cell/ lipid matrix. Cationic surfactants interact with skin proteins via polar interactions and hydrophobic binding. Hydrophobic interaction between surfactant chains and the protein result in pendant ionic head groups and subsequently swelling of the stratum corneum. [23] Cationic molecules are more destructive to skin tissues causing a greater increase in flux than anionic surfactants. [32] [Table 2] illustrates the role of cationic surfactants as penetration enhancers. | Table 2: Application of cationic surfactants as penetration enhancer in transdermal drug delivery
Click here to view |
Non-ionic surfactants
Nonionic surfactants, which are a safe class of enhancers, also offer a means of enhancing drug permeation through the skin. Nokhodchi et.al.[33] reported two -possible mechanisms by which the rate of transport is enhanced using nonionic surfactants.
- Firstly the surfactant may penetrate into the intercellular regions of stratum corneum, increase fluidity and eventually solubilize and extract lipid components.
- Secondly penetration of surfactant into the intercellular matrix followed by interaction and binding with keratin filaments may result in a disruption within the corneocyte. [33]
In addition non ionic surfactants are able to emulsify sebum, thereby enhancing the thermodynamic coefficient of drugs and allowing it to penetrate into the cells more effectively. [7]
Polysorbates which are a prominently safe class of surfactants offer a means of enhancing drug permeation through the skin. Polysorbate surfactants [Figure 2] demonstrated a significant increase of drug permeation up to 13 -fold when applied to hairless mouse skin. [34] Polysorbate 80 contains the ethylene oxide and a long hydrocarbon chain and this feature imparts both lipophilic and hydrophilic characteristics to this enhancer, allowing it to partition between lipophilic mortar substance and the hydrophilic domain. [35] Sorbitan monopalmitate, sorbitan trioleate, polyoxyl 8 stearate, polyoxyethylene 20 cetyl ether, or polyoxyethylene 2 oleyl ether 10% (w/w) significantly enhanced the percutaneous absorption of flufenamic acid and sodium salicylate when incorporated into white petrolatum USP ointment base. [36],[ 37]
The effect of nonionic surfactant on the rate of the permeation of drug compound through membranes from a formulation is highly dependent on the physical state of surfactant and its concentration in the locality of the membrane. [38] [Table 3] presents the mostly used nonionic surfactants in TDDS as penetration enhancers. | Table 3: Application of nonionic surfactants as penetration enhancer in transdermal drug delivery
Click here to view |
Zwitterionic surfactants
Ridout et.al. studied the action of five zwitterionic surfactants on the barrier function of hairless mouse skin and suggested that solubilization of stratum corneum lipids may be an important mechanism of penetration enhancement. The surfactants considered for study were dodecylbetaine, hexadecylbetaine, hexadecylsulfobetaine, N, N-dimethyl -N-dodecyl amine oxide, dodecyltrimethylammonium bromide. [39]
| Regulatory Aspects of Surfactants | | |
Safety has always been the most important requirement and the most studied when dealing with pharmaceutical drugs. In the United States, the food and drug administration (FDA) has published listings in the code of federal regulations (CFR) for GRAS substances that are generally recognized as safe. [59]
In general, nonclinical and clinical studies are required to demonstrate the safety of a new surfactant before use. The US FDA has published a guidance document for industry on the conduct of nonclinical studies for the safety evaluation of new pharmaceutical excipients. [60] This guidance not only provides the types of toxicity data to be used in determining whether a potential new excipient is safe, but also describes the safety evaluations for excipients proposed. The document also depicts testing strategies for pharmaceuticals proposed for short -term, intermediate, and long -term use. [60] More importantly, this guidance highlights the importance of performing risk -benefit assessments on proposed new excipients in the drug products while establishing permissible and safe limits for the excipients.It is often possible to assess the toxicology of an excipient in a relatively efficient manner. Existing human data for some excipients can substitute for certain nonclinical safety data. In addition, an excipient with documented prior human exposure under circumstances relevant to the proposed use may not require evaluation with a full battery of toxicology studies. [60]
| Conclusion | | |
The effect of surfactants on the enhancement of drug permeation through skin has been well reviewed. Research in this area has proved the usefulness of surfactants as chemical penetration enhancer in the transdermal drug delivery. In many instances they have been found to be more effective than other enhancers. Focus should be on skin irritation and toxicity with a view to select from a wide range of surfactants.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]
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Seeking better topical delivery technologies of moisturizing agents for enhanced skin moisturization |
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| Hyeongmin Kim,Jeong Tae Kim,Sonia Barua,Seung-Yup Yoo,Seong-Chul Hong,Kyung Bin Lee,Jaehwi Lee | | Expert Opinion on Drug Delivery. 2017; : 1 | | [Pubmed] | [DOI] | | | 3 |
Surfactants from itaconic acid: Toxicity to HaCaT keratinocytes in vitro, micellar solubilization, and skin permeation enhancement of hydrocortisone |
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| Angela Abruzzo,Nicola Armenise,Federica Bigucci,Teresa Cerchiara,Mireia Broch Gösser,Chiara Samorě,Paola Galletti,Emilio Tagliavini,David M. Brown,Helinor J. Johnston,Teresa F. Fernandes,Barbara Luppi | | International Journal of Pharmaceutics. 2017; 524(1-2): 9 | | [Pubmed] | [DOI] | | | 4 |
Development of medicated foams that combine incompatible hydrophilic and lipophilic drugs for psoriasis treatment |
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| Janja Mirtic,Foteini Papathanasiou,Žane Temova Rakuša,Mirjam GosencaMatjaž,Robert Roškar,Julijana Kristl | | International Journal of Pharmaceutics. 2017; 524(1-2): 65 | | [Pubmed] | [DOI] | | | 5 |
Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin Penetration Enhancers |
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| Pajaree Sakdiset,Hiroaki Todo,Kenji Sugibayashi | | CHEMICAL & PHARMACEUTICAL BULLETIN. 2017; 65(8): 776 | | [Pubmed] | [DOI] | | | 6 |
Formulation and characterization of acetate based ionic liquid in oil microemulsion as a carrier for acyclovir and methotrexate |
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| Shalini Kandasamy,Muhammad Moniruzzaman,Magaret Sivapragasam,Muhammad Rashid Shamsuddin,Mohamed Ibrahim Abdul Mutalib | | Separation and Purification Technology. 2017; | | [Pubmed] | [DOI] | | | 7 |
Galactosyl Pentadecene Reversibly Enhances Transdermal and Topical Drug Delivery |
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| Monika Kopecná,Miloslav Machácek,Eva Prchalová,Petr Štepánek,Pavel Drašar,Martin Kotora,Katerina Vávrová | | Pharmaceutical Research. 2017; | | [Pubmed] | [DOI] | | | 8 |
Voriconazole-loaded nanostructured lipid carriers (NLC) for drug delivery in deeper regions of the nail plate |
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| Kamilla Amaral David Rocha,Anna Paula Krawczyk-Santos,Lígia Marquez Andrade,Luana Clara de Souza,Ricardo Neves Marreto,Tais Gratieri,Stephânia Fleury Taveira | | International Journal of Pharmaceutics. 2017; 531(1): 292 | | [Pubmed] | [DOI] | | | 9 |
Combination Treatment of Citral Potentiates the Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with Pirarubicin for Colorectal Cancer |
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| Zhiyuan Fang,Yu Wang,Hao Li,Shuaishuai Yu,Ziying Liu,Zhichao Fan,Xiaomin Chen,Yuying Wu,Xuebo Pan,Xiaokun Li,Cong Wang | | Molecular Pharmaceutics. 2017; 14(10): 3588 | | [Pubmed] | [DOI] | | | 10 |
Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines |
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| Sunali Bhatnagar,James J. Kwan,Apurva R. Shah,Constantin-C Coussios,Robert C. Carlisle | | Journal of Controlled Release. 2016; | | [Pubmed] | [DOI] | | | 11 |
Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats |
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| Hend Mohamed Abdel-Bar,Rihab Osman,Amal Youssef Abdel-Reheem,Nahed Mortada,Gehanne A.S. Awad | | Biomacromolecules. 2016; 17(2): 407 | | [Pubmed] | [DOI] | | | 12 |
Pickering emulsions for skin decontamination |
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| Alicia Salerno,Marie-Alexandrine Bolzinger,Pauline Rolland,Yves Chevalier,Denis Josse,Stéphanie Briançon | | Toxicology in Vitro. 2016; | | [Pubmed] | [DOI] | | | 13 |
Efficient Percutaneous Delivery of the Antimelanogenic Agent Glabridin Using Cationic Amphiphilic Chitosan Micelles |
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| Haruyoshi Seino,Yukari Arai,Norio Nagao,Noriyasu Ozawa,Kazuhiko Hamada,Andrzej T Slominski | | PLOS ONE. 2016; 11(10): e0164061 | | [Pubmed] | [DOI] | | | 14 |
A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin |
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| Mahendra Shukla,Swati Jaiswal,Abhisheak Sharma,Pradeep Kumar Srivastava,Abhishek Arya,Anil Kumar Dwivedi,Jawahar Lal | | Drug Development and Industrial Pharmacy. 2016; : 1 | | [Pubmed] | [DOI] | | | 15 |
Safety Assessment of Dialkyl Sulfosuccinate Salts as Used in Cosmetics |
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| Monice M. Fiume,Bart Heldreth,Wilma F. Bergfeld,Donald V. Belsito,Ronald A. Hill,Curtis D. Klaassen,Daniel C. Liebler,James G. Marks,Ronald C. Shank,Thomas J. Slaga,Paul W. Snyder,F. Alan Andersen | | International Journal of Toxicology. 2016; 35(3_suppl): 34S | | [Pubmed] | [DOI] | | | 16 |
Safety data on 19 vehicles for use in 1?month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity |
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| Guy Healing,Tabassum Sulemann,Peter Cotton,Jayne Harris,Adam Hargreaves,Rowena Finney,Sarah Kirk,Carolin Schramm,Clare Garner,Perrine Pivette,Lisa Burdett | | Journal of Applied Toxicology. 2016; 36(1): 140 | | [Pubmed] | [DOI] | | | 17 |
Current and emerging formulation strategies for the effective transdermal delivery of HIV inhibitors |
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| Anthony S Ham,Robert W Buckheit | | Therapeutic Delivery. 2015; 6(2): 217 | | [Pubmed] | [DOI] | | | 18 |
Transdermal delivery of tadalafil using a novel formulation |
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| Jong-Suep Baek,Cheong-Weon Cho | | Drug Delivery. 2015; : 1 | | [Pubmed] | [DOI] | | | 19 |
Skin transport of PEGylated poly(e-caprolactone) nanoparticles assisted by (2-hydroxypropyl)-ß-cyclodextrin |
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| Claudia Conte,Gabriella Costabile,Ivana d’Angelo,Marianna Pannico,Pellegrino Musto,Gianluca Grassia,Armando Ialenti,Pasquale Tirino,Agnese Miro,Francesca Ungaro,Fabiana Quaglia | | Journal of Colloid and Interface Science. 2015; 454: 112 | | [Pubmed] | [DOI] | | | 20 |
Transdermal deferoxamine prevents pressure-induced diabetic ulcers |
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| Dominik Duscher,Evgenios Neofytou,Victor W. Wong,Zeshaan N. Maan,Robert C. Rennert,Mohammed Inayathullah,Michael Januszyk,Melanie Rodrigues,Andrey V. Malkovskiy,Arnetha J. Whitmore,Graham G. Walmsley,Michael G. Galvez,Alexander J. Whittam,Michael Brownlee,Jayakumar Rajadas,Geoffrey C. Gurtner | | Proceedings of the National Academy of Sciences. 2015; 112(1): 94 | | [Pubmed] | [DOI] | | | 21 |
Formulation of cellulose film containing permeation enhancers for prolonged delivery of propranolol hydrocloride |
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| Federica Bigucci,Angela Abruzzo,Teresa Cerchiara,Maria Caterina Gallucci,Barbara Luppi | | Drug Development and Industrial Pharmacy. 2015; 41(6): 1017 | | [Pubmed] | [DOI] | | | 22 |
Validation of the combined ATR-FTIR/tape stripping technique for monitoring the distribution of surfactants in the stratum corneum |
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| Magdalena Hoppel,Dieter Baurecht,Evelyn Holper,Denise Mahrhauser,Claudia Valenta | | International Journal of Pharmaceutics. 2014; 472(1-2): 88 | | [Pubmed] | [DOI] | | | 23 |
Novel delivery system of curcumin through transdermal route using sub-micronized particles composed of mesoporous silica and oleic acid |
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| Fayez Hamam,Mayyas Al-Remawi | | Journal of Functional Foods. 2014; 8: 87 | | [Pubmed] | [DOI] | | | 24 |
Synergistic effect of chemical penetration enhancer and iontophoresis on transappendageal transport of oligodeoxynucleotides |
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| Keng-Chih Liu,Colin R. Green,Raid G. Alany,Ilva D. Rupenthal | | International Journal of Pharmaceutics. 2013; 441(1-2): 687 | | [Pubmed] | [DOI] | | | 25 |
Colloidochemical aspects of transdermal drug delivery (review) |
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| N. M. Zadymova | | Colloid Journal. 2013; 75(5): 491 | | [Pubmed] | [DOI] | | | 26 |
Quality by design approach to prepare oleoyl alginate derivative and its use in transdermal delivery |
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| Mayyas Al-Remawi,Fayez Hamam,Mohammed Hamaidi | | Pharmaceutical Development and Technology. 2013; : 1 | | [Pubmed] | [DOI] | | | 27 |
Surfactant and temperature effects on paraben transport through silicone membranes |
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| Waters, L.J. and Dennis, L. and Bibi, A. and Mitchell, J.C. | | Colloids and Surfaces B: Biointerfaces. 2013; 108: 23-28 | | [Pubmed] | | | 28 |
Formulation, Characterization and evaluation of an optimized microemulsion formulation of griseofulvin for topical application |
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| Aggarwal, N. and Goindi, S. and Khurana, R. | | Colloids and Surfaces B: Biointerfaces. 2013; 105: 158-166 | | [Pubmed] | | | 29 |
Synergistic effect of chemical penetration enhancer and iontophoresis on transappendageal transport of oligodeoxynucleotides |
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| Liu, K.-C. and Green, C.R. and Alany, R.G. and Rupenthal, I.D. | | International Journal of Pharmaceutics. 2013; 441(1-2): 687-692 | | [Pubmed] | | | 30 |
Surfactant and temperature effects on paraben transport through silicone membranes |
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| Laura J. Waters,Laura Dennis,Aisha Bibi,John C. Mitchell | | Colloids and Surfaces B: Biointerfaces. 2013; 108: 23 | | [Pubmed] | [DOI] | | | 31 |
Formulation, characterization and evaluation of an optimized microemulsion formulation of griseofulvin for topical application |
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| Nidhi Aggarwal,Shishu Goindi,Ranjit Khurana | | Colloids and Surfaces B: Biointerfaces. 2013; 105: 158 | | [Pubmed] | [DOI] | | | 32 |
Methods to Assess the Protective Efficacy of Emollients against Climatic and Chemical Aggressors |
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| Romain Roure,Marion Lanctin,Virginie Nollent,Christiane Bertin | | Dermatology Research and Practice. 2012; 2012: 1 | | [Pubmed] | [DOI] | | | 33 |
Methods to assess the protective efficacy of emollients against climatic and chemical aggressors |
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| Roure, R. and Lanctin, M. and Nollent, V. and Bertin, C. | | Dermatology Research and Practice. 2012; 2012(864734) | | [Pubmed] | |
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