Transdermal, with enhanced skin

Transdermal Drug Delivery System with Enhanced Skin Permeability... 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

Kushner J, Kim D, So PTS, Blankschtein D, Langer RS. Dual-channel two-photon microscopy study of transdermal transport in skin treated with low-frequency ultrasound and a chemical enhancer. Journal of Investigative Dermatology 2007, 127, 2832-2846. 

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. 

Because of the low permeability of the skin to many drugs, trans-dermal delivery has limited applications. The low permeability is attributed primarily to the stratum comeum, the outermost skin layer which consists of flat, dead cells filled with keratin fibers surrounded by lipid bilayers. One common method of increasing the passive transdermal diffusional drug flux involves pretreating the skin with a skin permeation enhancer. 

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. 

The transdermal permation of glyceryl trinitrate encapsulated in AOT-reversed micelles was compared with that of an aqueous solution, and an enhancement in permeation was found as well as the absence of skin irritation [161]. 

The use of skin permeation enhancers in combination for synergistic effects has been studied in the transdermal literature (70). Such synergistic methods can be grouped in three categories (i) combination of two physical methods, e.g., ultrasound and iontophoresis (71-75) (ii) combination of a physical method with a chemical enhancer, e.g., use of ultrasound with sodium lauryl sulfate or isopropyl myristate (76-80) and (iii) combination of two chemicals, e.g., terpenes and propylene glycol (46,81-88). Numerous studies have been published on using combination of two physical methods or use of a physical method in conjunction with a chemical enhancer. Use of a physical method, by itself or in combination with another physical method, increases application cost for delivery purposes as mentioned before. In addition, there are unexplored safety and membrane recovery issues associated with these methods. A few reports have also been published on the use of a mixture of chemical enhancers for enhancing transdermal delivery. Typically, such studies use... 

In general, increased tissue wetness promotes transdermal delivery of both hydrophilic and lipophilic permeants. However, Bucks and Maibach [3] cautioned against too wide a generalization, stating that occlusion does not necessarily increase percutaneous absorption and may not always enhance transdermal delivery of hydrophilic compounds. Further, they warned that occlusion could irritate skin with clear implications for the design and clinical application of transdermal and topical preparations. 

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