<p>Comparisons of in vitro Fick’s first law, lipolysis, and in vivo rat models for oral absorption on BCS II drugs in SNEDDS</p>

Abstract

Purpose The objective of this study was to compare the in vitro Fick’s first law, in vitro lipolysis, and in vivo rat assays for oral absorption of Biopharmaceutical Classification Systems Class II (BCS II) drugs in self-nanoemulsifying drug delivery system (SNEDDS), and studied drugs and oils properties effects on the absorption. Methods The transport abilities of griseofulvin (GRI), phenytoin (PHE), indomethacin (IND), and ketoprofen (KET) in saturated water solutions and SNEDDS were investigated using the in vitro Madin-Darby canine kidney cell model. GRI and cinnarizine (CIN) in medium-chain triglycerides (MCT)-SNEDDS and long-chain triglycerides (LCT)-SNEDDS were administered in the in vivo SD rat and in vitro lipolysis models to compare the oral absorption and the distribution behaviors in GIT and build an in vitro-in vivo correlation (IVIVC). Results In the cell model, the solubility of GRI, PHE, IND, and KET increased 6–8 fold by SNEDDS, but their permeability were only 18%, 4%, 8%, and 33% of those of their saturated water solutions, respectively. However, in vivo absorption of GRI-SNEDDS was twice that of the GRI suspension and those of CIN-SNEDDS were 15–21 fold those of the CIN suspension. In the lipolysis model, the GRI% in aqueous and pellet phases of MCT were similar to that in LCT. In contrast, the CIN% in the aqueous and pellet phases were decreased but that of the lipid phase increased. In addition, an IVIVC was found between the CIN% in the lipid phase and in vivo relative oral bioavailability ( F r ). Conclusion The in vitro cell model was still a suitable tool to study drug properties effects on biofilm transport and SNEDDS absorption mechanisms. The in vitro lipolysis model provided superior oral absorption simulation of SNEDDS and helped to build correlation with in vivo rats. The oral drug absorption was affected by drug and oil properties in SNEDDS.

Liquid and Solid Self-Emulsifying Drug Delivery Systems (SEDDs) as Carriers for the Oral Delivery of Azithromycin: Optimization, In Vitro Characterization and Stability Assessment

“…Excipients selection was mainly based on their ability to solubilize the highest amounts of the AZM. The impact of lipids classes as long carbon chain triglycerides (LCT) and medium carbon chain triglycerides (MCT) was observed, as such differences in carbon chain lengths were reported to have an influence on drug solubilization potential and the ability to facilitate the emulsification process [38,39]. Extra attention was given to include excipients with previously reported abilities to loosen the cellular TJ for the possibility of enhancing the drug paracellular route diffusion.…”

<p>A Non-Lipolysis Nanoemulsion Improved Oral Bioavailability by Reducing the First-Pass Metabolism of Raloxifene, and Related Absorption Mechanisms Being Studied</p>

“…After lipolysis, RAL was rapidly released and the chylomicrons were formed by lipolytic products of LNE and then uptake into the blood or lymphatic system, resulting in a higher C max than those of SUSP and NNE. 15,38 In contrast, the RAL encapsulated in NNE was slowly released and resulted in the lower C max . Although no evident difference between the oral bioavailability of NNE and LNE in rats (Table 3), the bioavailability of NNE in pigs was significantly higher than that of LNE (Table 4).…”

“…32 Furthermore, the intermolecular forces of the ionic bond between RAL and LA were enhanced, resulting in smaller globule sizes. 15,33 Although RAL was most soluble in ethanol, which could efficiently improve its emulsification efficiency, the weight ratio of ethanol in the pre-NE was limited to 10%-20% as ethanol did not retain its solubilization capacity after dispersion in an aqueous system because of its water solubility, which may lead to drug precipitation. 34,35 Therefore, we identified that IP:LA (1:2, w/w), Cremophor RH40, and ethanol in a 5:3:2 weight ratio in pre -NNE was used to prepare the optimal RAL-NNE.…”

“…In this way, the drug undergoes the first-pass metabolism after the digestion of NE in the GIT. [13][14][15] In contrast, only a small part of NNEs can be hydrolyzed and of the majority of non-lipolysis nanoemulsion (NNE) are absorbed as the globules or mixed micelles which maybe differ with LNE. Therefore, in this study, we attempted to develop a NNE that could not only enhance the solubility and permeability of drugs but also avoid the first-pass metabolism of drugs in the GIT by the different absorption mechanisms.…”

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

“…where the flux (J) of a drug through the GI barrier wall, which is defined as dM, the cumulative transport mass during dt, depends on the diffusion area (S), permeability coefficient (P) of the drug, and the drug concentration (C) in the GI lumen (assuming sink conditions) [45]. From this equation, it can be estimated that increasing the drug solubility can improve absorption of a poorly water-soluble drug.…”