Effect of pH on in vitro permeation of ondansetron hydrochloride across porcine buccal mucosa.
The influence of drug concentration, pH in donor chamber, and 1-octanol/buffer partition coefficient on transbuccal permeation of ondansetron hydrochloride (pKa, 7.4) across porcine buccal mucosa was studied by using an in-line Franz type diffusion cell at 37 degrees C. The pH was adjusted to several values and the solubility of the drug in different pH was measured. Solubility of ondansetron hydrochloride decreases with increasing pH. The permeability of the drug was evaluated at different donor pH and drug concentrations. Permeability of un-ionized (Pu) and ionized (Pi) species of drug was calculated by fitting the data to a mathematical model. The steady state flux increased linearly with the donor concentration (r2 = 0.9843) at pH 7.4. The permeability coefficient and the partition coefficient of the drug increased with increasing pH. The values of Pu and Pi were 4.86 x 10(-6) cm/sec and 7.18 x 10(-7) (c)m/sec, respectively. The observed permeability coefficients and the permeability coefficients calculated from the mathematical model at various pH showed good linearity (r2 = 0.9799). The total permeability coefficient increased with increasing the fraction of un-ionized form of the drug. The drug permeated through buccal mucosa by a passive diffusion process. The non-ionized species of drug penetrated well through buccal mucosa and the permeation was a function of pH. Transbuccal delivery is a potential route for the administration of ondansetron hydrochloride.
Mashru
R C
RC
Pharmacy Department, Faculty of Technology and Engineering, The M. S. University of Baroda, Gujarat, India. vsutariya@yahoo.co.in
Sutariya
Vijay B
VB
Sankalia
Mayur G
MG
Sankalia
Jolly M
JM
D000465:Algorithms; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009061:Mouth Mucosa / Q000378:metabolism*; D017294:Ondansetron / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D012995:Solubility; D013552:Swine
D000932:Antiemetics; D017294:Ondansetron