In silico prediction of drug permeability across buccal mucosa.
OBJECTIVE
To develop and validate a computational model capable of predicting buccal permeability based on various structural and physicochemical descriptors.


METHODS
Apparent permeability coefficients (K(p)) of 15 different drugs across porcine buccal mucosa were determined. Multiple linear regression (MLR) and maximum likelihood estimations (MLE) were used to develop the model based on a training set of 15 drugs with permeability as the response variable and the various descriptors as the predictor variables. The final model was validated with an external data set consisting of permeability values obtained from the literature.


RESULTS
Drug permeabilities ranged from 30 x 10(-6) (nimesulide) to 3.3 x 10(-9) cm/s (furosemide). Regression analysis showed that 95% of the variability in permeability data can be explained by a model that includes molecular volume, distribution coefficient at pH 6.8, number of hydrogen bond donors, and number of rotatable bonds. Smaller molecular size, high lipophilicity, lower hydrogen bond capability and greater flexibility were important for permeability. The buccal model was found to have a good predictive capability.


CONCLUSIONS
A simple model was developed and validated for predicting the buccal drug permeability. This model will be useful in assessing the feasibility of drugs for transbuccal delivery.
Kokate
Amit
A
Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California 95211, USA.
Li
Xiaoling
X
Williams
Paul J
PJ
Singh
Parminder
P
Jasti
Bhaskara R
BR
D000278:Administration, Buccal; D000818:Animals; D016014:Linear Models; D008954:Models, Biological; D015394:Molecular Structure; D009061:Mouth Mucosa / Q000378:metabolism*; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D013552:Swine
D004364:Pharmaceutical Preparations