The oral-mucosal route is one of the early routes of administration for non-invasive systemic drug delivery. This route avoids first-pass metabolism and provides quick drug entry into the systemic circulation. Oral mucosal route includes buccal, sublingual and ginigival routes of drug delivery.Different in-silico models were developed to study the relationship between oral mucosal permeability and physico-chemical and molecular properties of drugs. Drugs with diverse physicochemical and molecular properties such as, molecular volume, molecular weight, partition coefficient, distribution coefficient, pKa, total polar surface area, hydrogen bond acceptors and donors, number of rotatable bonds, solubility and melting point were used to develop the models. It was shown that owing to differences in barrier properties, the permeability of drugs can vary between buccal and sublingual mucosa. Oral-mucosal permeability was found to be dependent on molecular volume, distribution coefficient, 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 oral-mucosal permeability. Due to the relatively hydrophilic nature of the oral-mucosa, in addition to the lipophilic drugs, oral-mucosal delivery can be an attractive alternative for the hydrophilic or charged drugs which otherwise have poor permeability across more lipophilic biological barriers. Nimesulide was used as a model drug to study the effect of the degree of ionization on sublingual permeation of ionized and unionized drug species. It was shown that ionized drug species can permeate across the sublingual mucosa and contribute significantly to the total drug flux.The analysis of the contributions of drug properties to the permeability provided mechanistic insights in to drug permeation across oral mucosa from molecular structure perspective. This data can serve as an initial evaluation tool to screen prospective drug candidates for sublingual delivery.

Relationship between drug properties and oral-mucosoal route of drug delivery

247th National Meeting (2014)

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