Percutaneous Penetration Modifiers and Formulation Effects: Thermal and Spectral Analyses

Abstract

Abstract. The study investigated the formulation effects of laurocapram and iminosulfurane derived penetration modifiers on human stratum corneum using thermal and spectral analyses. Firstly, formulations of penetration modifiers were assessed as enhancers/retardants using the model permeant, diethyl-m-toluamide followed by investigation of their mechanisms of action using differential scanning calorimetry (DSC) and attenuated total reflectance Fourier-transform infra-red spectroscopy. The penetration modifiers investigated were laurocapram, 3-dodecanoyloxazolidin-2-one (N-0915), S,Sdimethyl-N-(4-bromobenzoyl) iminosulfurane (DMBIS), S,S-dimethyl-N-(2-methoxycarbonylbenzenesulfonyl) iminosulfurane (DMMCBI) and tert-butyl 1-dodecyl-2-oxoazepan-3-yl-carbamate (TBDOC) that were formulated in either water, propylene glycol (PG), ethanol or polyethylene glycol 400 (PEG 400). The results explain the mechanism for the first time why an enhancer can become a retardant or vice versa depending upon the vehicle in which it is applied to the skin. DSC indicated that penetration modifier formulations enhanced permeation of active mainly by disruption and fluidization of the stratum corneum lipid bilayers while IR data indicated characteristic blue shifts with decreases in peak intensity. On the other hand, DSC of penetration modifier formulations showing retardation depicted elevated T m2 with a strengthening of lipid-protein complex while IR results indicated formation of multiple peaks around 1,738 cm −1 transition in stratum corneum spectra suggesting retardation may be caused by organization of SC lipids by increased H-bonding.

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

“…[29] A decrease in the peaks of CH 2 symmetric stretching at 2850 cm −1 or asymmetric stretching at 2920 cm −1 are indicative of lipid extraction. [30,31] This suggests that CAGE acts as a lipid extractor to improve permeability of drugs across the skin. All spectra were deconvoluted into individual peaks ( Figure 5) to facilitate comparison of the pre-and post-incubation spectrum.…”

Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal Contagiousness

“…Citric acid, ascorbic acid, and acetone could not increase penetration as good as PG, while penetration of voriconazole in formulation is directly proportional to concentration of PG, moreover penetration ability of neem oil was dependent over solvent in which it was solubilized 26 and PG solubilized both hydrophilic and hydrophobic penetration enhancers too and it inhibits partition of penetration enhancer in SC, so PG was used as penetration enhancer in concentration of 1-10% w/w or solvent for penetration enhancer for prospective study.…”

Effect of the Various Solvents on the <i>In Vitro</i> Permeability of Vitamin B₁₂ through Excised Rat Skin

“…Increase in enthalpy and transition T m1 by Labrafil and Capryol may due to bilayer cohesion [20], which is in contrast to lipid extraction and fluidization. The shift in Tm to lower temperatures can be interpreted as disruption of the lipid bilayer and the irreversible denaturation of proteins in the SC layer of skin, while decrease in ∆H is related to fluidization of lipid in lipid bilayer and lipid -protein complex [14][15][16][17][18][19].…”

“…T 1 and T 2 transitions appeared to be due to melting of lipids and irreversible denaturation of intracellular keratin, respectively. Previous studies on the thermotropic behavior of rat skin indicates three Table 2: Decrease in mean peak height (± SD), compared with control (untreated skin) of assymmetric (Asy) and symmetric (Sym) C-H stretching and C=O stretching absorbance of abdominal hydrated whole skin rat following treatment with different solvents (mean ± standard deviation, n = 3) Note: %D = decrease in peak height (%) [16].…”

“…They showed that Tm 1 corresponds to lipid transformation from a lamellar to disordered state, Tm 2 is due to the melting of lipid -protein( keratin) complex [2,16], or the disruption of polar head groups of lipids [14][15][16][17], Tm3 is known to occur during the irreversible denaturation of proteins in the SC [16].…”