Engineering of a novel optimized platform for sublingual delivery with novel characterization tools: in vitro evaluation and in vivo pharmacokinetics study in human

Abstract

The aim of this work was to develop a novel and more efficient platform for sublingual drug delivery using mosapride citrate (MSP) as a model drug. The engineering of this delivery system had two stages, the first stage was tuning of MSP physicochemical properties by complexation with pure phosphatidylcholine or phosphatidylinositol enriched soybean lecithin to form MSP-phospholipid complex (MSP-PLCP). Changes in physicochemical properties were assessed and the optimum MSP-PLCP formula was then used for formulation into a flushing resistant platform using two mucoadhesive polymers; sodium alginates and sodium carboxymethylcellulose at different concentrations. Design of experiment approach was used to characterize and optimize the formulated flushing resistant platform. The optimized formulation was then used in a comparative pharmacokinetics study with the market formulation in human volunteers. Results showed a marked change in MSP physicochemical properties of MSP-PLCP compared to MSP. Addition of mucoadhesive polymers to flushing resistant platform at an optimum concentration balanced between desired mucoadhesive properties and a reasonable drug release rate. The optimized formulation showed significantly a superior bioavailability in humans when compared to the market sublingual product. Finally, the novel developed sublingual flushing resistant platform offers a very promising and efficient tool to extend the use of sublingual route and widen its applications.

Biopolymer Drug Delivery Systems for Oromucosal Application: Recent Trends in Pharmaceutical R&D

“…Lipophilic substances usually contain a benzene ring, a steroid nucleus, a carbohydrate chain or halogens in their structure. The ability of lipophilic molecules to cross the lipid barrier depends on their lipid solubility, which is determined by logP [81]. In general, small and lipophilic molecules with logP around 1.6-3.3 are well absorbed across the oral mucosa, whereas drugs with higher logP values are poorly absorbed due to their low water solubility [16].…”

Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals

“…Recently, [20] revealed the increase in drug release from the buccal films at lower pH attributed to the faster release characteristics of organic acid from the buccal films. Further, the ability of a drug to penetrate the oral mucosa depends on the lipid solubility, denoted by the oil/water partition coefficient [21]. Commercial formulations for oral transmucosal delivery have a log p valve (octanol/water) above 2.0, representing the drugs are 100 times more readily soluble in octanol than in water.…”