Effect of pH on In Vitro Permeation of Ondansetron Hydrochloride Across Porcine Buccal Mucosa

Abstract

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.

Transdermal skin patch based on reduced graphene oxide: A new approach for photothermal triggered permeation of ondansetron across porcine skin

“…5B). These values are comparable to that reported by Mashru et al at pH 7.4 with an ODS flux of J = 2.52 μg cm − 2 h − 1 [58]. The results are also in line with the permeation parameters of ODS through exercised hairless mouse skin with a flux of J = 4.04 μg cm − 2 h − 1 reported by Gwak et al using binary diethylene glycol monoethyl ether (DGME)/propylene glycol manocaprylate (PGMC) vehicles with a DGME/PGMC ratio of 1/100 [45].…”

Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT3 antagonists tropisetron and ondansetron

“…OCT1 may transport serotonin itself and, by its expression in the intestine, may mediate reuptake of serotonin released from the enterochromaffine cells upon cytostatic chemotherapy. 28 However, in this case OCT1 loss-of-function variants would be expected to result in an increased The pKa value of ondansetron is according to Maschru et al, 29 and all other physicochemical properties were calculated using ADMET Predictor Software 4.0 (Simulations Plus, Lancaster, CA, USA).…”

Porcine Buccal Mucosa as an In Vitro Model: Relative Contribution of Epithelium and Connective Tissue as Permeability Barriers

“…Permeation studies of drugs were reported to have been carried out using varying thicknesses of porcine buccal mucosa—500 µm,21, 25–29 500–600 µm,30–35 600–800 µm,7, 11, 36 770 ± 280 µm,37 736 ± 110 µm,38 and 1000 µm 39–41. Since, it is assumed that only the upper one third region of the epithelium acts as a permeability barrier, little attention was paid to the exact thickness of the tissue used in these permeation studies.…”