Influence of modified cyclodextrins on solubility and percutaneous absorption of celecoxib through human skin.
We evaluated the ability of two modified cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP-beta-Cyd) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd), to influence the percutaneous absorption through isolated human stratum corneum and epidermis (SCE) of celecoxib (CCB). Previous studies demonstrated that DM-beta-Cyd includes the drug, producing a significant increase of water solubility (0.5 mg/ml at 25 degrees C) and dissolution rate of CCB. In this work chemical-physical characterization studies were performed to evaluate the ability of HP-beta-Cyd to include CCB. We showed that only an external interaction could exist between CCB and HP-beta-Cyd that positively influences the water solubility of the drug (0.12 mg/ml at 25 degrees C for CCB-HP-beta-CyD system and 4.12 x 10(-3) mg/ml at 25 degrees C for free CCB). In vitro percutaneous experiments were performed using samples in solution and in suspension containing different Cyd concentrations. Both HP-beta-Cyd and DM-beta-Cyd enhanced drug flux through SCE by means of an increase of dissolution rate of the drug as well as a direct action on the stratum corneum (SC). Histological analysis of treated SCE showed a protective effect of the two Cyds towards an invasive action shown by CCB on SC.
Pharmaco-Chemical Department, Faculty of Pharmacy, University of Messina, V.le Annunziata, I-98168 Messina, Italy. cventura@pharma.unime.it
C A
CA
Ventura
S
S
Tommasini
A
A
Falcone
I
I
Giannone
D
D
Paolino
V
V
Sdrafkakis
M R
MR
Mondello
G
G
Puglisi
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010539:Permeability; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D000068579:Celecoxib