Effect of physicochemical properties on sublingual absorption
Poster Number
21A
Introduction/Abstract
Oral mucosal administration of drugs such as sublingual, supralingual or buccal are the preferred route when a drug exhibits large first pass effect after oral delivery. Rapid onset of action of drugs is anticipated due to rapid absorption (sublingual, buccal and supralingual) and ability to elude first pass effect. However, rapid oral clearance does not mean all the drug is completely absorbed via oral mucosa, and some could be cleared saliva. [1] Many marketed sublingual drug products have shown to have high sublingual bioavailability compared to oral bioavailability. [3-5]
Purpose
The first objective of this study is to compare the extent of sublingual absorption to total bioavailability of the drug products. Our second objective is to correlate calculated sublingual pharmacokinetic parameter (Area Under Curve) with physicochemical properties of the active pharmaceutical ingredients.
Method
Plasma concentration data of the marketed sublingual drug products SAPHRIS(Asenapine), DSUVIA (Sufentanil), INTERMEZZO (Zolpidem tartarate), and ABSTRAL (Fentanyl) were collected from literature [2-5]. Non-compartmental analysis was performed using Phoenix WinNonlin version 8.3; (Certara, L.P., St. Louis, MO, USA) and pk parameters such as AUC, Cmax, and Tmax were estimated. Bioavailability was calculated using AUCsublingual/AUCiv for saphris, dsuvia and intermezzo. The AUC of the active pharmaceutical agents were compared with physicochemical properties such as log partition coefficient (logP), Hydrogen bond donors (HBD), melting point (MP) etc.
Results
DSUVIA shows 4.35-fold increase in AUC when given sublingually compared to oral AUC. The rate of absorption is 20 times higher than that of oral. Similarly, SAPHRIS shows 10.39-fold increase in sublingual AUC when compared to oral AUC. Rate of absorption is 29.50 times higher than oral route. Furthermore, INTERMEZZO shows 83- fold increase in AUC and 1.55 times the rate of absorption. Of all the physicochemical parameters correlated, AUC was most influenced by log P, when compared to MP, HBD.
Sublingual drug products show higher bioavailability when compared to oral. This could be due to rapid absorption through sublingual mucosa and avoidance of the first pass effect. The AUC of model drugs were found correlated to their log P values (R2=0.98) with significance of p<0.005.
Significance
Sublingual drug products show enhanced bioavailability when compared to oral drug products. Despite of this potential, only few marketed drug products are available. This is due to the lack of reliable guiding system which can predict in-vivo behavior in preclinical stage. Our goal is to correlate sublingual absorption with drug structure to identify influential physicochemical property. This study will provide fundamental knowledge for sublingual drug design from physicochemical perspective.
Location
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Effect of physicochemical properties on sublingual absorption
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Oral mucosal administration of drugs such as sublingual, supralingual or buccal are the preferred route when a drug exhibits large first pass effect after oral delivery. Rapid onset of action of drugs is anticipated due to rapid absorption (sublingual, buccal and supralingual) and ability to elude first pass effect. However, rapid oral clearance does not mean all the drug is completely absorbed via oral mucosa, and some could be cleared saliva. [1] Many marketed sublingual drug products have shown to have high sublingual bioavailability compared to oral bioavailability. [3-5]
