Influence of non-ionic surfactants, pH and propylene glycol on percutaneous absorption of piroxicam from cataplasm.
The influence of pH in the formulation, ethylene oxide chain length of polyoxyethylene (POE) non-ionic surfactants and addition of propylene glycol (PG) on percutaneous absorption of piroxicam (Px) from cataplasm was investigated in guinea-pig in vivo. The area under the plasma concentration of Px curve until 8 h after the application (AUC(0-8)) increased with increasing the cataplasm base pH up to 6.5 and then plateaued from pH 6.5 to 7.2. Px solubility in water increased markedly with increasing pH from pH 6 as Px is a weak acid and its pK(a) is 5.3. The ionic form of Px in the cataplasm was suspected to contribute to the percutaneous absorption of Px. The percutaneous absorption of Px from the cataplasms containing 5% of POE non-ionic surfactants with various POE lengths were examined. The parabolic relation between the Px absorption and the POE length was observed. POE length from 5 to 15 enhanced percutaneous absorption to a greater extent. An attempt was also made to examine the influence of the addition of PG to the formulation containing POE (9) lauryl ether. The addition of 20% PG to the formulation significantly increased the Px concentration in plasma, compared to 0, 5, 10 and 15% PG. Skin and cutaneous muscle concentrations significantly increased by addition of 20% PG, compared to those by 0% PG but not in deeper muscle.
Okuyama
H
H
Central Research Laboratories, SSP Co., Ltd., Nanpeidai 1143, Narita, Chiba, Japan. ohkiro@nrm.root.or.jp
Ikeda
Y
Y
Kasai
S
S
Imamori
K
K
Takayama
K
K
Nagai
T
T
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients / Q000494:pharmacology*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010894:Piroxicam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011409:Propylene Glycols / Q000494:pharmacology*; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D011409:Propylene Glycols; D013501:Surface-Active Agents; D010894:Piroxicam