AAPS PharmSciTech

, Volume 11, Issue 3, pp 1068–1083 | Cite as

Percutaneous Penetration Modifiers and Formulation Effects: Thermal and Spectral Analyses

Research Article


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,S-dimethyl-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.

Key words

differential scanning calorimetry enhancers infra-red spectroscopy penetration modifiers retardants stratum corneum 



Attenuated total reflectance Fourier-transform infra-red spectroscopy




S,S-Dimethyl-N-(4-bromobenzoyl) iminosulfurane


S,S-dimethyl-N-(2-methoxycarbonylbenzenesulfonyl) iminosulfurane


Differential scanning calorimetry


Mean enthalpy


Hydrogen bond


Honestly significantly different



PEG 400

Polyethylene glycol 400


Propylene glycol


Stratum corneum


tert-Butyl 1-dodecyl-2-oxoazepan-3-yl-carbamate


Mean transition temperature



The authors express gratitude to Dr James Chapman (University of South Carolina, Columbia) for providing N-0915 and TBDOC. In addition, we acknowledge the assistance of Drs. A. Joy, D. Bolikal, S. Murthy, J. Khan and J. Kohn from the NJ Center for Biomaterials for providing compounds laurocapram, DMMCBI, and DMBIS and DSC facility. Partial funding provided by the NJ Center for Biomaterials, Rutgers—The State University of New Jersey.


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Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  1. 1.Ernest Mario School of PharmacyRutgers—The State University of New JerseyPiscatawayUSA
  2. 2.New Jersey Center for BiomaterialsRutgers—The State University of New JerseyPiscatawayUSA

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