Penetration enhancement of ibuprofen from supersaturated solutions through human skin.
Systematic investigations on the diffusion of ibuprofen (IBU) from supersaturated solutions through human epidermis are reported. Significant flux enhancement was obtained from supersaturated solutions compared to the saturated solution. Hydroxypropyl methylcellulose (HPMC), when used as an additive was found to be effective in maintaining the high activity state at high degrees of saturation (DS). The increase in the flux was proportional to the DS. In the presence of 2-hydroxypropyl-beta-cyclodextrin (CD) at DS 2 and 3 a lower flux was observed compared to HPMC. At DS 5 a higher flux enhancement was found suggesting that CD might act as a penetration enhancer at certain CD/drug ratios. Studies on the mechanism of stabilisation of HPMC and CD on IBU crystallisation from supersaturated systems showed that HPMC acts as a growth inhibitor and habit modifier whereas CD does not influence the crystallisation process.
Iervolino
M
M
Dipartimento di Chimica Farmaceutica e Tossicologica, Universitá degli Studi di Napoli Federico II, Via D. Montesano 49, 80131, Napoli, Italy.
Cappello
B
B
Raghavan
S L
SL
Hadgraft
J
J
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D003460:Crystallization; D003505:Cyclodextrins / Q000494:pharmacology*; D004058:Diffusion; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007785:Lactose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010078:Oxazines; D012867:Skin / Q000378:metabolism*; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D010078:Oxazines; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D007052:Ibuprofen