Dammarane sapogenins (protopanaxadiol/PPD and protopanaxatriol/PPT) are the end metabolites of ginsenosides, with the removal of sugar side chains. A number of cell-culture, animal, and human studies have confirmed that PPD and PPT are at least 5~10 times as active as their precursor saponins.
However, dammarane sapogenins are lipophilic and not water-soluble, therefore, its oral absorption in traditional preparations is poor. Researchers from China Medical Science Academy found that the bioavailability of oral PPD is poor, due to its poor solubility and first-pass effect in the liver. Therefore, a new drug delivery method is needed to improve PPD’s absorption.
Dripping pill is a novel drug delivery method using solid dispersion and cosolvency technologies. Dripping pill uses water-miscible matrix to completely dissolve insoluble compounds. When the mixture solidifies to form micropills through dripping, the medicinal compounds are embedded in the matrix in a molecular form (solid dispersion). When the dripping pill dissolves, the matrix will help herbal compounds solublize in aqueous environment (Cosolvency), and ready for rapid absorption by oral mucosa and GI tract. This method is especially useful for hydrophobic herbal ingredients, which has a low solubility in GI tract despite high transepithelial permeability.
Due to above obvious advantages, dripping pills could be an effective drug delivery method for dammarane sapogenins. In dripping pills, the microcrystals of lipophilic PPD or PPT are surrounded tightly by water-soluble matrix. Dripping pill formulation will greatly increase the solubility of PPD or PPT because its water-soluble matrix forms a homogeneous suspension with PPT or PPT, giving the latter a good access to epithelial cells of the GI tract. If taking sublingually, its bioavailability and blood concentration will be further increased due to the prevention of the first-pass effect by the liver, resulting in a satisfied clinical efficacy.
[Polybasic research on the biopharmaceutical characteristics of 20 (S)-protopanaxadiol].
Yao Xue Xue Bao. 2013 Mar;48(3):411-6
Abstract
In this study, the biopharmaceutical properties of 20 (S)-protopanaxadiol (PPD) were studied. Firstly, the equilibrium solubility and apparent oil/water partition coefficient of PPD were used to predict the absorption in vivo. Meanwhile the membrane permeability and absorption window were studied by Caco-2 cell model and single-pass intestinal perfusion model. Furthermore, the bioavailability and metabolism were combined to study the absorption properties and metabolic properties in vivo. All of them were used to provide theoretical and practical foundation for designing PPD preparation. The results showed that PPD is poorly water-soluble, and the equilibrium solubility in water is only 35.24 mg x L(-1). The oil-water partition coefficient is 46.21 (logP = 1.66). By Caco-2 cell model, the results showed PPD uptake in general, and it also has efflux. By in situ intestinal perfusion model, the results showed that the absorption of PPD in the intestine is good, and the effective permeability coefficient were duodenum > jejunum > ileum > colon. The oral bioavailability of PPD was 29.39%. It was not well. Metabolic studies showed PPD in vivo presented a wide spread metabolism. So the main factors that restricted oral bioavailability of PPD were the poor solubility and first-pass effect.
