Effect of Freezing and Type of Mucosa on Ex Vivo Drug Permeability Parameters

Abstract

Abstract. The porcine esophageal mucosa has been proposed as a substitute for the buccal mucosa barrier on ex vivo permeability studies mainly due to its large surface area as well as its easier preparation. Therefore, this study compared the ex vivo permeability parameters of two drugs (carmabazepine (CBZ) and triamcinolone acetonide (TAC)) with different permeabilities and physicochemical properties through buccal and esophageal mucosae using a Franz diffusion cell system and HPLC as detection method. The freezing effects on drug permeability parameters were also evaluated by comparing them when fresh and frozen tissues were used. The barrier properties were not affected by the freezing process since the obtained parameters for both drugs were similar in frozen and fresh tissues (buccal and esophageal mucosae). However, an increase of CBZ retention was shown in frozen tissues. Fresh and frozen esophageal mucosae provided higher permeation of TAC than on buccal mucosae while the obtained permeability parameters for CBZ were similar on both mucosae. According to our results, porcine esophageal mucosa could be used as a substitute for buccal mucosa on ex vivo studies involving CBZ but not TAC. Frozen tissues could be used as substitute for fresh tissues in both cases. However, any substitution should be done with care and only if previous tests were performed, because the results could differ depending on the tested drug.

Ex Vivo Correlation of the Permeability of Metoprolol Across Human and Porcine Buccal Mucosa

“…Thus, a tissue sample from porcine buccal mucosa was fixed directly after slaughter at the abattoir, and no difference was found between the prefrozen and the fresh tissue samples. Previous studies have showed that a freezing cycle may influence the histology of the tissue, but not the permeability, which is in accordance with the findings of the present study wherein a histological comparison showed that fresh buccal mucosa, fixed just after slaughter, showed no difference to the prefrozen tissue sample (data not shown). The impact of the pH treatments during the permeability study was examined for the lowest and the highest pH values, that is, pH 7.4 and 9.0.…”

“…The lower permeability of metoprolol in the human model could be because of (1) an adherent mucus gel layer acting as an additional barrier that might not be preserved in the prefrozen porcine model and/or (2) a difference in protein and/or lipid composition of the human and porcine tissue that affect the barrier properties. Evaluation of the difference in drug permeability using fresh and prefrozen tissues has been performed in numerous studies, and there is no consensus regarding the significance of freezing on the permeability of various drugs with different physicochemical properties. However, there is a general agreement that freezing of tissues does not affect the lipid permeability barrier, which is responsible for the barrier properties of small lipophilic molecules …”

“…Evaluation of the difference in drug permeability using fresh and prefrozen tissues has been performed in numerous studies, and there is no consensus regarding the significance of freezing on the permeability of various drugs with different physicochemical properties. However, there is a general agreement that freezing of tissues does not affect the lipid permeability barrier, which is responsible for the barrier properties of small lipophilic molecules …”

Formulation and evaluation of sublingual delivery of piroxicam using thermosensitive polymer with an inverted Franz diffusion cell

“…The pH (Model 215 pH meter; Denver Instrument, Bohemia, NY, USA) of the prepared formulations and formulations with different volume of artificial saliva are given in Table a,b, respectively. The artificial saliva solution was prepared using salts in DI water and adjusted to alkaline pH 7.2 …”

Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa

“…The mucosal membrane was carefully separated by removing the underlying connective tissues using surgical scissors. The separated mucosal membrane was washed with deionized water and then with simulated saliva (pH 6.2) [10] . Porcine buccal mucosa (3 cm diameter) was glued on the surface of a glass slab.…”