Effect of drug chirality on the skin permeability of ibuprofen

• Published in: International journal of pharmaceutics Vol. 386; no. 1; pp. 71 - 76
• Main Authors: Cilurzo, F., Alberti, E., Minghetti, P., Gennari, C.G.M., Casiraghi, A., Montanari, L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-02-2010; Elsevier
• Subjects: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Biological and medical sciences; Chemistry, Pharmaceutical; Chirality; Diffusion; Dimethylpolysiloxanes - chemistry; Dosage Forms; Drug Compounding; Epidermis - metabolism; Excipients - chemistry; General pharmacology; Human skin permeability; Humans; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Ibuprofen - metabolism; Kinetics; Medical sciences; Medicated plaster; Models, Biological; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - chemistry; Propylene Glycol - chemistry; S-Ibuprofen; Skin Absorption; Solubility; Stereoisomerism; Supersaturation; Technology, Pharmaceutical - methods; Tissue Adhesives - chemistry; Transition Temperature; Medicated plaster; Supersaturation; S-Ibuprofen; Chirality; Human skin permeability; Human; Drug; Prostaglandin-endoperoxide synthase; Pharmaceutical technology; Enzyme; Enzyme inhibitor; Permeability; Non steroidal antiinflammatory agent; Ibuprofen; Arylpropionic acid derivatives; Skin; Oxidoreductases
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2009.10.053

The
in vitro passive diffusion of
S-ibuprofen (
S-IB) and
RS-ibuprofen (
RS-IB) through human epidermis was determined to study the effects of drug chirality.
S-IB has a lower melting point (
T
m
=
54
°C) than
RS-IB (
T
m
=
77
°C) and, therefore, a greater solubility (
S-IB: 127
±
1
μg/mL;
RS-IB: 81
±
1
μg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit
® RL and propylene glycol as antinucleant agents. The
in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of
S-IB from saturated solutions resulted statistically higher than those of
RS-IB (
p
<
0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate (
p
>
0.17). The latter unexpected results could be explained considering that the
RS-IB or
S-IB
in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.