Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Abstract

The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH 3 -PPD). Optimized SMEDDS formulations for 25-OCH 3 -PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH 3 -PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH 3 -PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH 3 -PPD via the oral route.

<p>Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity</p>

“…Mobile phase was composed of 0.1% TFA in water and a mixture of acetonitrile: methanol (17:1) at a ratio of 10:90. The elute time was 15 mins with the column temperature maintained at 30°C 30. The flow rate was set at 1.3 mL/min, with the detection wavelength of 210 nm.…”

Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD, a natural inhibitor of the MDM2 oncogene: Nanoparticle preparation, characterization,in vitroandin vivoanti-prostate cancer activity, and mechanisms of action

“…An ideal solution to the bioavailability problem is to develop a formulation which protects the drug in its intact form and increases its absorption and bio-stability. Recently, a self-emulsifying drug delivery system (SEDDS) for GS25 was developed to allow oral administration, but there was no evidence of improved anticancer efficacy of the drug when it was administered in an emulsion [ 30 ]. Therefore, it is of high importance to develop an orally active formulation for GS25 that can provide improved anticancer efficacy and minimal toxicity.…”

Natural Product Ginsenoside 20(S)-25-Methoxyl-Dammarane-3β, 12β, 20-Triol in Cancer Treatment: A Review of the Pharmacological Mechanisms and Pharmacokinetics

“…Along with pharmacokinetic studies for 25-OCH 3 -PPD, several studies were performed to develop delivery systems improving the oral bioavailability of 25-OCH 3 -PPD, which is the major drawback for the development of anticancer agent. Although the paper focuses on 20(S)-25-OCH 3 -PPD, we comprehensively reviewed the research outcome related to both 20(R)-and 20 (S)-25-OCH 3 -PPD to give the reader pharmaceutical insights as much as possible A self-microemulsifying drug delivery system (SMEDDS) was shown to enhance oral bioavailability of 20(S)-25-OCH 3 -PPD (Cai et al, 2014). A SMEDDS is an isotropic mixture of oil, surfactant, and possibly co-surfactant, which forms fine oil in water (o/w) emulsions upon mild agitation when exposed to an aqueous media, such as gastrointestinal (GI) fluids.…”

“…A nanoemulsion system employing phospholipid complexes was designed to increase the oral bioavailability of 20(R)-25-OCH 3 -PPD (Zhang et al, 2016). The phospholipid complexes, the main components of the nanoemulsion system fabricated, have amphiphilic properties so that they can act as surfactant with considerably lower toxicity than the surfactants used for the SMEDDS, in the previous study of Cai et al (2014), where large amounts of surfactants such as Cremorphor ® EL could cause gastrointestinal irritation and be toxic (Gelderblom et al, 2001). Phospholipid complexes with 20(R)-25-OCH 3 -PPD were produced at a different molar ratio and formulated to the nanoemulsion system in 1% PEG400 water solution.…”