Rapidly dissolving formulations for quick absorption during pain episodes: ibuprofen.
OBJECTIVE
Pain or its associated trauma impairs oral absorption of drugs due, perhaps, to a diminished disintegration and dissolution rate secondary to suppression of the vagal nervous system. We first examined whether ibuprofen absorption is impaired on suppressing vagus nerve activity in a rat model. Secondly, we examined if ibuprofen absorption in rats during vagal suppression and in humans experiencing dental pain is improved by enhancing disintegration and dissolution rate of the administered formulation.


METHODS
Vagal suppression was achieved in rats by administering 20 mg/kg propantheline i.p. 2 h and 1 h before gastric gavage of 20 mg/kg ibuprofen as small crushed pieces of a regular release and a fast-dissolving ibuprofen caplets. In humans, after surgical removal of wisdom teeth and emergence of pain, 2 A 200 mg ibuprofen as regular released (n = 14) and fast-dissolving (n = 12) caplets were administered. Serial blood sample were collected for bioavailability studies.


RESULTS
Vagal suppression resulted in significantly decreased absorption rate of ibuprofen enantiomers following administration of the regular release but not after fast-dissolving formulation. Human dental pain was associated with significantly slower absorption of ibuprofen enantiomers from the regular released as compared with the fast-dissolving caplets. Within the first hour post-dose the area under the plasma drug concentration-time curve was raised to 2.7-fold (p < 0.05) after the fast-dissolving as compared with the regular release formulations. There was a 1-h difference in the peak concentration time (tmax) between the two caplets.


CONCLUSIONS
Impaired drug absorption appears to be due to slow disintegration and dissolution encountered during pain episodes.
Jamali
F
F
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada. fjamali@pharmacy.ualberta.ca
Aghazadeh-Habashi
A
A
D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D016503:Drug Delivery Systems; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012995:Solubility; D013237:Stereoisomerism; D013607:Tablets; D013997:Time Factors; D014081:Tooth Extraction / Q000379:methods; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology
D018712:Analgesics, Non-Narcotic; D013607:Tablets; D007052:Ibuprofen