Synergistic Effect of Isopropyl Myristate and Glyceryl Monocaprylate on the Skin Permeation of Pentazocine

Abstract

While most drugs are administered orally, there are numerous advantages to the percutaneous route. These advantages include the potential for sustained release, controlled input kinetics, improved patient compliance, and avoidance of first-pass metabolism in the gastrointestinal tract. However, the stratum corneum (SC), the outermost layer of the epidermis, is the principal rate limitation to percutaneous absorption. The SC layer is composed of keratin-enriched corneocytes embedded in a multilamellar lipid matrix, which mainly comprises ceramides, cholesterol and free fatty acids.1,2) Both physical methods (SC stripping, iontophoresis, phonophoresis and microneedle) and chemical methods (synthesis of lipophilic analogues and skin permeation enhancers) are used to promote the delivery of drugs across the skin. Of these methods, the most widely implemented approach to increase percutaneous absorption is the use of skin permeation enhancers, which ideally cause a temporary, reversible reduction in the barrier function of the SC in order to facilitate safe and effective drug delivery through the skin.3) In theory, there are two potential pathways through the SC: the transcellular pathway, which involves permeation across the corneocytes and multilamellar lipid matrix, and the intercellular pathway, which involves permeation via the lipid domains between the corneocytes. Within the corneocytes, the major site of action would be the keratin fibrils and their associated water molecules.4) Within the intercellular route, it is proposed that enhancers may interact with the polar head groups and between the hydrophobic tails of the lipid bilayers. The lipid matrix of the SC, therefore, is a target of action for permeation enhancers.5) Considering the structure of the SC and the continuity of the lipid barrier, interaction with SC intercellular lipids is of crucial importance for the effectiveness of permeation enhancers. 5)Pentazocine (PTZ, M w : 285.42, log P: 3.08 (pH 7.0)), a benzomorphan derivative, is an opioid analgesic that has mixed opioid agonist-antagonist function. It is considered to be a partial agonist or weak antagonist at the m-receptor and an agonist at the k-receptor. PTZ is used for the relief of moderate to severe pain. Oral administration of PTZ has the disadvantage of low bioavailability (approximately 20%) due to extensive first-pass metabolism. In addition, PTZ has a short half-life of 2-3 h and requires frequent dosing in order to maintain an optimal therapeutic concentration. There is a clinical need for PTZ to be made available as a long-acting formulation for chronic pain management. 6)We have already reported the effects of glyceryl monocaprylate (GEFA-C 8 ) as an enhancer of the permeation of PTZ in isopropyl myristate (IPM) solution across excised hairless mouse skin. We found that the flux of PTZ combined with both GEFA-C 8 and IPM was approximately 4 times higher than that with IPM alone. 7) Moreover, we demonstrated that a novel transdermal drug delivery system patch composed of Duro-Tak ...

Effect of Terpenes on the Skin Permeation of Lomerizine Dihydrochloride

“…Carbocyanine dyes with short alkyl chains partition between the aqueous and membrane phases in a membrane-potential-dependent manner, while the hydrophobic nature of long-chain carbocyanine dyes leads to their insertion into cells with their alkyl chains embedded in the lipid bilayer (51). Both fluorescent probes are used for visualization of the intercellular spaces in the SC (52,53).…”

Vehicle effects on human stratum corneum absorption and skin penetration

“…IPM, utilized as a substitute for skin lipid in SC model membranes (Ottaviani et al, 2006), can integrate into SC lipid chain packing and result in higher lipid fluidity (Brinkmann and Muller-Goymann, 2005; Furuishi et al, 2010). Since IPM is a non-volatile vehicle with high viscosity, the slow release of solute into SC induced lower SC absorption.…”

A Systematic Quantitative Evaluation of Permeation Enhancement Window: Transdermal Permeation Enhancing Dynamics Establishment and Molecular Mechanisms Characterization of Permeation Enhancer

“…The test conditions were based on previous literature. 22,23,24 The wavelength (λ) of the X-ray beam was 0.15406 nm. The sample SC (approximately 10 mg) was held in an aluminum sample holder, which was sealed with Kapton films on both sides.…”

“…There were two coexisting repeating units in the SC, characterized by repeat distances at 6.4 and 13.0 nm called short periodicity phase (SPP) and long periodicity phase (LPP). 31,32,33 The peak at S = 0.157 nm À1 can be assigned to the 2nd peak of LPP and S = 0.169 nm À1 can be assigned to the 1st peak of SPP, 22,24 and the profiles of SAXS were displayed in Fig. S7.…”