Improved Oral Bioavailability of BCS Class 2 Compounds by Self Nano-Emulsifying Drug Delivery Systems (SNEDDS): The Underlying Mechanisms for Amiodarone and Talinolol

Abstract

Multiple mechanisms are accountable for improved bioavailability and reduced variability of Class-2 compounds by SNEDDS: increased solubilization, reduced intraenterocyte metabolism and reduced P-gp efflux. SNEDDS effect is reversible and doesn't cause intestinal tissue or cell damage. These comprehensive findings can be used for intelligent selection of drugs for which oral bioavailability will improve upon incorporation into SNEDDS, based on recognition of the drug's absorption barriers and the ability of SNEDDS to overcome them.

Systematic development of optimized SNEDDS of artemether with improved biopharmaceutical and antimalarial potential

“…As the SNEDDS presents the drug in solubilized form in the blood in the form of nanostructured globules, it resulted in drastic augmentation in the bioavailable fraction and consequently the pharmacodynamic action (Bandyopadhyay et al, 2012;Elgart et al, 2013). Interestingly, a small edge in the efficacy of optimized MCT-SNEDDS over the LCT-SNEDDS throughout in vivo studies may be explained on the basis of literature reports.…”

“…Remarkable augmentation in the antimalarial activity of the drug can be rationally ascribed to the superior efficacy of the SNEDDS formulation, owing to significant improvement in the biopharmaceutical performance of the drug. Vital mechanistics through which SNEDDS may have helped in augmenting the oral drug absorption by circumnavigation of hepatic first-pass effect, inhibition of metabolism by gut cytochromes and of efflux by P-gp (Porter & Charman, 2001a;Porter et al, 2008;Singh et al, 2011b;Elgart et al, 2013;Singh et al, 2014;Beg et al, 2015b). Owing to enhanced oral drug absorption into the systemic circulation, more number of parasites were killed in case of the SNEDDS formulations, as is clearly evident from the percent parasitemia count in the blood smear till day ''8'' P.I.…”

“…These primarily constitute the isotropic mixtures of lipids, surfactants, cosurfactants and/or cosolvents, which upon spontaneous emulsification in presence of gastrointestinal fluid produce ultrafine oil-in-water nanoemulsion with particle size less than 100 nm (Singh et al, 2009). Many literature reports have vouched the merits of SNEDDS in addressing the issues of low oral bioavailability of drugs, owing to its holistic approach for enhancing the solubility, circumventing the hepatic first-pass effect, increasing the intestinal permeability, inhibiting the P-glycoprotein (P-gp) efflux and potentiating drug absorption through intestinal lymphatic pathways (Porter & Charman, 2001a;Elgart et al, 2013;Singh et al, 2014;Beg et al, 2015b).…”

“…As lipids primarily offer solubilization of the drug in their selection of the type of lipids (i.e., mono/di/triglycerides) primarily influences the drug loading and in vivo absorption of the drugs (Singh et al, 2009;Elgart et al, 2013;. On the other hand, the surfactants and cosolvents tend to impart drug solubilization and emulsification capacities to the formulations (Bandyopadhyay et al, 2012).…”

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

“…Transport studies were not carried out until the cell monolayer was formed. 25 Caco-2 transport studies were initiated by removing the medium from both sides of the monolayer, followed by replacement with apical (AP) and basolateral (BL) buffers prewarmed to 37°C. The cell monolayers were incubated in a shock shaker for 30 min at 37°C (100 cycles/min) until equilibration.…”