for drug absorption with respect to oral drug delivery. Moreover the mucosal lining of the oral cavity offers some important advantages such as rich vascularization, rapid cellular recovery, easy accessibility for both dosage form administration and removal and the possibility to avoid acid hydrolysis in the gastrointestinal tract and first-pass effect. Porcine buccal mucosa is widely used for in vitro permeation studies, usually by Franz-type diffusion cells, due to its close resemblance to the human buccal mucosa and similar permeability characteristics. However, the use of animal mucosa has several drawbacks, while artificial membranes may provide higher repeatability and quickness in the experiments. Moreover, Franz diffusion cells are a static method and the very small volume of the acceptor medium does not allow the maintenance of sink conditions, thus leading to drug permeation underestimation. In a previous work we developed an in vitro method based on the use of artificial membranes able to provide a rapid and reliable evaluation and prediction of the intestinal absorption properties of drugs. Therefore, as a continuation of this work, the aim of the present study was to develop a new in vitro method for the assessment of drug buccal absorption, based on the use of suitable artificial membranes purposely tuned. Naproxen was selected as reference model drug in this preliminary study. Firstly, the apparent drug permeation (Papp) was calculated both with Franz diffusion cells and Sartorius apparatus, by using freshly excised pig buccal mucosa. Once determined the target Papp value to be obtained with the artificial membrane, the effect on drug permeability of the composition of the lipid mixture used for support impregnation was investigated by using mixture design, namely a special response surface study where the response is function of the different proportions of the components. Due to possible interference of membrane lipidic components, the assay of permeated drug was performed by HPLC analysis. The use of mixture design allowed optimization of the relative content of the different lipid mixture components, in order to reach the prefixed Papp value of the model drug. The proposed method seems to offer an interesting and effective alternative to the use of animal membranes for rapidly obtaining highly reproducible in vitro permeation data for a reliable prediction of the drug buccal permeation. This could be very useful for a preliminary fast screening of new drug compounds in the early stages of the drug discovery process.

Assessment of artificial membranes aimed for in vitro study of drug buccal permeation using experimental design / Mura, P.; Casella, G.; Valèrio, S.; Orlandini, S.; Furlanetto, S.; Maestrelli, F.. - ELETTRONICO. - (2015), pp. 90-90. (Intervento presentato al convegno XXIII National Meeting on Medicinal Chemistry and 9th Young Medicinal Chemists Symposium-XXIII NMMC & 9th NPCF tenutosi a Fisciano, Salerno, Italy nel 6-9 Settembre 2015).

Assessment of artificial membranes aimed for in vitro study of drug buccal permeation using experimental design

MURA, PAOLA ANGELA;CASELLA, GIADA;ORLANDINI, SERENA;FURLANETTO, SANDRA;MAESTRELLI, FRANCESCA
2015

Abstract

for drug absorption with respect to oral drug delivery. Moreover the mucosal lining of the oral cavity offers some important advantages such as rich vascularization, rapid cellular recovery, easy accessibility for both dosage form administration and removal and the possibility to avoid acid hydrolysis in the gastrointestinal tract and first-pass effect. Porcine buccal mucosa is widely used for in vitro permeation studies, usually by Franz-type diffusion cells, due to its close resemblance to the human buccal mucosa and similar permeability characteristics. However, the use of animal mucosa has several drawbacks, while artificial membranes may provide higher repeatability and quickness in the experiments. Moreover, Franz diffusion cells are a static method and the very small volume of the acceptor medium does not allow the maintenance of sink conditions, thus leading to drug permeation underestimation. In a previous work we developed an in vitro method based on the use of artificial membranes able to provide a rapid and reliable evaluation and prediction of the intestinal absorption properties of drugs. Therefore, as a continuation of this work, the aim of the present study was to develop a new in vitro method for the assessment of drug buccal absorption, based on the use of suitable artificial membranes purposely tuned. Naproxen was selected as reference model drug in this preliminary study. Firstly, the apparent drug permeation (Papp) was calculated both with Franz diffusion cells and Sartorius apparatus, by using freshly excised pig buccal mucosa. Once determined the target Papp value to be obtained with the artificial membrane, the effect on drug permeability of the composition of the lipid mixture used for support impregnation was investigated by using mixture design, namely a special response surface study where the response is function of the different proportions of the components. Due to possible interference of membrane lipidic components, the assay of permeated drug was performed by HPLC analysis. The use of mixture design allowed optimization of the relative content of the different lipid mixture components, in order to reach the prefixed Papp value of the model drug. The proposed method seems to offer an interesting and effective alternative to the use of animal membranes for rapidly obtaining highly reproducible in vitro permeation data for a reliable prediction of the drug buccal permeation. This could be very useful for a preliminary fast screening of new drug compounds in the early stages of the drug discovery process.
2015
Atti del XXIII National Meeting on Medicinal Chemistry and 9th Young Medicinal Chemists Symposium-XXIII NMMC & 9th NPCF
XXIII National Meeting on Medicinal Chemistry and 9th Young Medicinal Chemists Symposium-XXIII NMMC & 9th NPCF
Fisciano, Salerno, Italy
Mura, P.; Casella, G.; Valèrio, S.; Orlandini, S.; Furlanetto, S.; Maestrelli, F.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1006211
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