Formulation study and anti-inflammatory efficacy of topical semi-solids containing a nitro ester of flurbiprofen.
A new nitro-oxybutylester of flurbiprofen (NO-FP) is a promising anti-inflammatory drug in the treatment of dermatological disorders, and the feasibility of its cutaneous administration was evaluated. Four different semi-solid formulations were evaluated in order to assess the influence of the composition on the drug amount retained in the stratum corneum and epidermis (SCE). The lipophilic ointment induced the highest NO-FP amount retained in the SCE and, therefore, skin permeation enhancers (Transcutol), Lauroglycol), oleic acid and isopropyl myristate) were added to this formulation. The in vitro NO-FP amounts retained in the SCE were correlated with the solubility parameters, and a good linear correlation was found (r(2) = 0.925). The formulation of the lipophilic ointment was optimized, and the activity of this preparation was verified in methyl-nicotinate-induced contact urticaria and UV-induced erythema obtaining good results in terms of efficacy and safety.
Minghetti
P
P
Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Italy. paola.minghetti@unimi.it
Casiraghi
A
A
Cilurzo
F
F
Tosi
L
L
Montanari
L
L
Trespidi
L
L
D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D003872:Dermatitis / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009539:Nicotinic Acids; D009824:Ointments; D011565:Psoriasis / Q000188:drug therapy; D012867:Skin / Q000187:drug effects; D012995:Solubility; D013997:Time Factors; D014466:Ultraviolet Rays; D014581:Urticaria / Q000139:chemically induced / Q000188:drug therapy
C478649:2-fluoro-alpha-methyl-(1,1'-biphenyl)-4-acetic acid 4-(nitro-oxy)butyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009539:Nicotinic Acids; D009824:Ointments; D005480:Flurbiprofen; C008473:methyl nicotinate