Modulation of dihydroavenanthramide D release and skin penetration by 1,2-alkanediols.
If a semisolid vehicle does not allow for the sufficient penetration of the incorporated drug, the addition of enhancers, e.g. glycols, is an option. Propylene glycol is most frequently applied in dermal products. Other 1,2-alkanediols like pentylene glycol were found to exhibit moisturizing effects and good anti-microbial activity. In the present study, the influence of propylene glycol and mainly butylene glycol (BuG) and pentylene glycol (PeG) on release and skin penetration of Dihydroavenanthramide D (DHAvD) was investigated. DHAvD release increased twice up to fourfold within 30 min if 2% of a mixture of BuG and PeG was added to a lipophilic as well as to a hydrophilic cream. Incorporation of single 1,2-alkanediols into the hydrophilic cream resulted in a linear slope of the released DHAvD amount with increasing chain length of the glycol. Trends found in the release model were also reflected in penetration studies on full thickness human breast skin using Franz diffusion cells. Here, the hydrophilic cream containing the BuG/PeG mixture was compared to the glycol-free reference. Already within 30 min the amount that penetrated into the viable skin layers doubled using the glycol-containing vehicle. After 300 min 12% of the applied dose was detected in the viable epidermis and dermis following application of the pure cream compared to 41% from the improved formulation. Dermal availability was further enhanced by administration of a polymer-stabilized hydrodispersion gel which also contained the glycol mixture. Due to their favorable biopharmaceutical and technological properties, longer chain 1,2-alkanediols represent a valuable class of ingredients for dermal products.
Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck Strasse 4, Halle/Saale, Germany. sandra.heuschkel@pharmazie.uni-halle.de
Sandra
S
Heuschkel
Johannes
J
Wohlrab
Gerhard
G
Schmaus
Reinhard H H
RH
Neubert
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D002072:Butylene Glycols / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D015194:Diffusion Chambers, Culture; D005260:Female; D006018:Glycols / Q000737:chemistry / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D008970:Molecular Weight; D009824:Ointments; D014677:Pharmaceutical Vehicles / Q000737:chemistry / Q000494:pharmacology*; D019946:Propylene Glycol / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
D002072:Butylene Glycols; D006018:Glycols; D006634:Histamine H1 Antagonists; D009824:Ointments; D014677:Pharmaceutical Vehicles; D062367:ortho-Aminobenzoates; C532345:dihydroavenanthramide D; D019946:Propylene Glycol