Transdermal penetrants penetration enhancers

Cyclic sulfoxides, lactones, lactams, and other heterocycles as transdermal penetration enhancers 99CLY107. 

Transdermal delivery of certain APIs is now common for the treatment of some medical conditions, and there are several excipients that are promoted as transdermal penetration enhancers. One of the earlier materials developed was laurocapram (Azone ). There is a detrimental interaction between laurocapram and mineral oil (liquid paraffin) whereby when both are included in the same formulation, the skin penetration-enhancing properties of laurocapram are lost. Such interactions have implications for extemporaneous mixing of different cream and ointment formulations in the pharmacy. 

Karande P, Jain A, Mitragotri S. Discovery of transdermal penetration enhancers by high throughput screening. Nature Biotechnol 2004 22 192-197. 

Finnin B, Morgan T. Transdermal penetration enhancers applications, limitations, and potential. J Pharm Sci 1999 88 955-958. 

Sasaki H, Kojima M, Nakamura J, Shibasaki J. Acute toxicity and skin irritation of pyr-rolidone derivatives as transdermal penetration enhancers. Chem Pharm Bull 1990 38 2308-2310. 

Wong, O., et al. 1989. Unsaturated cyclic ureas as new non-toxic biodegradable transdermal penetration enhancers. II. Evaluation study. Int J Pharm 52 191. 

The hydrosilylation of acetyl-protected allylglucoside with a Si-H-ended telechelic polysiloxane, followed by deprotection has also been described by Nagase et al. for the preparation of glyco-oligodimethylsiloxanes as transdermal penetration enhancers (Fig. 10) [16-18]. The status of the siloxane chain after deprotection has been checked by size exclusion chromatography (SEC). When they used MeOH/K COj for deprotection, they observed by SEC the formation of two peaks... 

T. Akimoto, K. Kawahara, Y. Nagase, T. Aoyagi, Macromol. Chem. Phys., 2000, 201(18), 2729-2734. Preparation of oligodimethylsiloxanes with sugar moiety at a terminal group as a transdermal penetration enhancer . 

Wong, O. Huntington, A. Nishihata, T. Rytting, J.H. New alkyl V V-Dialkyl-substituted amino acetates as transdermal penetration enhancers. Pharm. Res. 1989, 6, 286-295. 

Stearyl alcohol is used in cosmetics and topical pharmaceutical creams and ointments as a stiffening agent. By increasing the viscosity of an emulsion, stearyl alcohol increases its stability. Stearyl alcohol also has some emollient and weak emulsifying properties and is used to increase the water-holding capacity of ointments, e.g. petrolatum. In addition, stearyl alcohol has been used in controlled-release tablets, " suppositories, and microspheres. It has also been investigated for use as a transdermal penetration enhancer. ... 

Bodde, H. E., M. Ponec, A. P. IJzerman, A. J. Hoogstraate, M. A. I. Salomons, and J. A. Bouwstra. 1993. In vitro analysis of QSAR in wanted and unwanted effects of azacycloheptanones as transdermal penetration enhancers. In Pharmaceutical skin penetration enhancement, edited by K. A. Walters, and J. Hadgraft. New York Marcel Dekker, pp. 199-214. 

Michniak, B.B. Player, M.R. Sowell, J.W. S3mthesis and in vitro transdermal penetration enhancing activity of lactam N-acetic acid esters, J.Pharm.Sci., 1996, 85, 150-154... 

Godwin, D.A. and Michniak, B.B. (1999). Influence of drug lipophilicity on terpenes as transdermal penetration enhancers. Drug Dev. Ind. Pharm., 25 905-915. 

Sasaki, H., Kojima, M., Nakamura, J., and Shibasaki, J. (1990a). Acute toxicity and skin irritation of pyrrolidone derivatives as transdermal penetration enhancer, Chem. Pharm. Bull, 38 2308-2310. 

Perfusion of skin with transdermal-penetration-enhancing agents such as ethanol, DMSO-ds and propylene glycol was studied by in vitro P NMR [39]. Epidermal strips from abdominal pig skin were placed in a 10 mm O.D. NMR tube modified for continuous perfusion with buffered salt solution and a serial spectra were recorded on a Broker AMX500 spectrometer. Signal intensities for phosphomono- and di-esters PME and PDE, phosphocreatine PCr, inorganic phosphate Pi and nucleotide triphosphorate, >3-NTP were followed in time. Additional spectra were recorded when the perfusion medium contained dexamethasone. The dexamethasone perfusion resulted in a dose-dependent decrease in PCr and NTP levels and had an effect on PME metabolism. 

Wen, H., Xianxi, G., Lihai, X., Feng, M. (2009). Study on the mechanisms of chitosan and its derivatives used as transdermal penetration enhancers, 382,234-243. 

Different approaches have been used for the hydrosilylation of allylglycosides with various H-functional polysiloxanes [71, 78, 85-87], Glucopyranosyl- and cellobiosyl-terminated oligodimethylsiloxanes with thioether or ether linkages have been prepared and tested as transdermal penetration enhancers [87], The monosaccharide-modified compounds exhibited a pronounced permeation acceleration for antipyrine, while the disaccharide ether siloxane had no enhancing activity. 

An interesting feature of this polymer is its ability to act as a transdermal penetration enhancer. For example, the penetration profiles of indomethacin, a model... 

Mrozek et al. synthesized fourteen acyloxy derivatives of 5(S-cholic acid as novel potential transdermal penetration enhancers and intestinal drug absorption modifiers (Figure 49.6). Nontoxic bile acid/salt derivatives (as amphiphilic compounds) are used widely in drug formulations as excipients and can influence gastrointestinal solubility, absorption, and chemical/enzymatic stability of drugs. Transdermal penetration enhancers are special pharmaceutical excipients that interact with skin components to increase the penetration of drugs into blood circulation after topical application. Structure confirmation of all generated compounds was accomplished by H NMR, NMR, IR, and mass spectrometer (MS) spectroscopy. 

Walters, K.A. (1989). Penetration enhancers and their use in transdermal therapeutic systems. In Transdermal Drug Delivery — Development Issues and Research Initiatives, J. Hadgraft and R.H. Guy, eds. Marcel Dekker, New York, 197-246. 

The lack of significant impact of CPEs on transdermal delivery vehicles is related to the inherent nonspecific activity of CPEs in the different strata of the skin, as discussed earlier. This limitation may be overcome by utilization of mixtures of CPEs. Research has already shown that binary mixtures of CPEs provide increased permeation enhancement as well as increased safety compared to single enhancers. Such unique chemical combinations, called synergistic combinations of penetration enhancers or SCOPE formulations, offer new opportunities in transdermal drug delivery (46). 

Purdon C, Azzi C, Zhang J, Smith E, Maibach H. Penetration enhancement of transdermal delivery—current permutations and limitations. Crit Rev Ther Drug Carrier Systems 2004 21 97-132. 

Weichers J. Use of chemical penetration enhancers in transdermal drug delivery—possibilities and difficulties. Acta Pharmeceutica Nordica 1992 4 123-123. 

Jain A, Panchagnula R. Combination of penetration enhancers for transdermal drug delivery—studies with imipramine hydrochloride. Pharmazeutische Industrie 2004 66 478-482. 

Gwak H, Oh I, Chun I. Transdermal delivery of ondansetron hydrochloride effects of vehicles and penetration enhancers. Drug Dev Ind Pharm 2004 30 187-194. 

Kanikkannan N, Kandimalla K, Lamba S, Singh M. Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 2000 7 593-608. 

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