Role of Biorelevant Media in Estimation of in vitro Lipolysis and Food Impact on Self-emulsifying Drug Delivery Systems.

2020 ◽  
Vol 15 ◽  
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Small Intestine ◽  
Drug Delivery Systems ◽  
Food Effect ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Biorelevant Media ◽  
In Vitro Lipolysis ◽  
Fasted State

: Self-emulsifying drug delivery systems (SEDDS) includes self-micro emulsifying drug delivery system (SMEDDS) and self-nano emulsifying drug delivery system (SNEDDS) whose major benefits is reduction of inter/intra subject variability and food effect which may alter the pharmacological response of the drug. Oral intake of these formulations triggers the digestion process because of pancreatic lipase which emulsify/digest the lipidic ingredients of the formulation resulting into precipitation of the drug. As a tool to foresee in vivo medicament precipitation, in vitro lipolysis models are established. Biorelevant media play an important role to study the effect of in vitro lipolysis and food impact on the bioavailability of SEDDS formulations. It is vital to generate composition of fluids for both fed and fasting conditions of gastric, small intestine and colon to investigate the impact of in vitro lipolysis and food effect on the release behavior of drug from SEDDS. Fed/Fasted state simulated gastric fluid (Fe/FaSSGF), Fed/Fasted state simulated gastric fluid (Fe/FaSSIF) (Phosphate buffers) are first generation while Fa/FeSSIF-V2 (maleate) are second generation biorelevant media utilized for these studies. FaSSIF-V3 belongs to third generation which differs from other generations in the composition and source of bile salts. With updates in physiological data, it is vital to incorporate changes in the dissolution media to make it more biorelevant. This review paper mainly laid emphasis on the compositions of biorelevant media of gastric and small intestine for both fed and fasting conditions. In addition to these, applications of biorelevant to investigate effect of in vitro lipolysis and food on SEDDS are discussed with some recent research reports.

scholarly journals Interpolymer Complexes of Eudragit® Copolymers as Novel Carriers for Colon-Specific Drug Delivery

Polymers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1459
Author(s):  
Aleksandra V. Bukhovets ◽  
Nikoletta Fotaki ◽  
Vitaliy V. Khutoryanskiy ◽  
Rouslan I. Moustafine
Keyword(s):  
Drug Delivery ◽  
Photoelectron Spectroscopy ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Biorelevant Media ◽  
Simulated Intestinal Fluid ◽  
Swelling Properties ◽  
Interpolymer Complexes ◽  
Fasted State ◽  
The Media

Interpolymer complexes (IPC) based on Eudragit® EPO and Eudragit® S100 were investigated as potential carriers for oral controlled drug delivery to the colon. IPC samples were prepared by mixing copolymer solutions in organic solvents (ethanol, isopropanol:acetone mixture (60:40, % v/v) and tetrahydrofuran). According to the data of elemental analysis, FTIR-spectroscopy, X-ray photoelectron spectroscopy and thermal analysis these IPCs have excess of anionic copolymer (Eudragit® S100) in their structure; they are stabilized by hydrogen and ionic intermacromolecular bonds and do not include free copolymer domains. IPC have pH-independent swelling properties in the media mimicking gastrointestinal tract (GIT) conditions and provide colon-specific delivery of indomethacin in buffer solutions (pH 1.2; 5.8; 6.8; 7.4) and in biorelevant media (fasted state simulated gastric fluid, fasted state simulated intestinal fluid—version 2 and fasted stated simulated colonic fluid).

scholarly journals Predicting Oral Absorption of fenofibrate in Lipid-Based Drug Delivery Systems by Combining In Vitro Lipolysis with the Mucus-PVPA Permeability Model

2021 ◽  
Vol 110 (1) ◽  
pp. 208-216
Author(s):  
Margherita Falavigna ◽  
Mette Klitgaard ◽  
Ragna Berthelsen ◽  
Anette Müllertz ◽  
Gøril Eide Flaten
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
Permeability Model ◽  
In Vitro Lipolysis

Using in vitro lipolysis and SPECT/CT in vivo imaging to understand oral absorption of fenofibrate from lipid-based drug delivery systems

2020 ◽  
Vol 317 ◽  
pp. 375-384 ◽  
Author(s):  
Thuy Tran ◽  
Peter Bønløkke ◽  
Cristina Rodríguez-Rodríguez ◽  
Zeynab Nosrati ◽  
Pedro Luis Esquinas ◽  
...  
Keyword(s):  
Drug Delivery ◽  
In Vivo Imaging ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
In Vitro Lipolysis

scholarly journals Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 267 ◽  
Author(s):  
Tao Yi ◽  
Jifen Zhang
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Commercial Application ◽  
Simulated Gastric Fluid ◽  
Structural Transitions

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

scholarly journals DEVELOPMENT OF MUCOADHESIVE CHITOSAN-BASED DRUG DELIVERY SYSTEM

2018 ◽  
Vol XXIII ◽  
pp. 103-113
Author(s):  
Mariya Konovalova ◽  
Balzhima Shagdarova ◽  
Anastasia Zubareva ◽  
Alexander Generalov ◽  
Maria Grechikhina ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Small Intestine ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Mucous Membranes ◽  
Colon Cell ◽  
Reactive Groups ◽  
Low Toxicity ◽  
Positively Charged

Chitosan is a highly versatile biopolymer characterised by low toxicity, biocompatibility, and slow but complete biodegradation in the human body, possessing multiple reactive groups. One of the most well-known properties of positively charged chitosan derivatives is their ability to bind mucous membranes. The aim of this work was the analysis of mucoadhesion of unmodified 20 kDa chitosan and its hydrophobic (HC) and hydrophobic quaternised (QHC) derivatives in vitro and ex vivo. Unmodified chitosan formed large aggregates in vitro in keratinocyte and colon cell cultures and ex vivo in murine small intestine and muscle explants. At the same time, HC and especially QHC bound cells in vitro and ex vivo in a fine dotted manner, as evidenced by confocal microscopy. Such a pattern of hydrophobic derivatives distribution provides the possibility to develop mucoadhesive drug delivery systems with increased local drug release and improved chitosan biodegradation.

scholarly journals Metabolic Stability of D-Allulose in Biorelevant Media and Hepatocytes: Comparison with Fructose and Erythritol

Foods ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 448 ◽  
Author(s):  
Maeng ◽  
Yoon ◽  
Chun ◽  
Kim ◽  
Jang ◽  
...  
Keyword(s):  
Calorific Value ◽  
Rat Hepatocytes ◽  
Gastric Fluid ◽  
Metabolic Stability ◽  
Simulated Gastric Fluid ◽  
Pharmacokinetic Studies ◽  
Food Ingredient ◽  
Biorelevant Media ◽  
Simulated Intestinal Fluid

D-allulose, a C-3 epimer of D-fructose, is a rare monosaccharide used as a food ingredient or a sweetener. In the present study, the in vitro metabolic stability of D-allulose was examined in biorelevant media, that is, simulated gastric fluid (SGF) and fasted state simulated intestinal fluid (FaSSIF) containing digestive enzymes, and in cryopreserved human and rat hepatocytes. The hepatocyte metabolic stabilities of D-allulose were also investigated and compared with those of fructose and erythritol (a sugar-alcohol with no calorific value). D-allulose was highly stable in SGF (97.8% remained after 60 min) and in FaSSIF (101.3% remained after 240 min), indicating it is neither pH-labile nor degraded in the gastrointestinal tract. D-allulose also exhibited high levels of stability in human and rat hepatocytes (94.5–96.8% remained after 240 min), whereas fructose was rapidly metabolized (43.1–52.6% remained), which suggested these two epimers are metabolized in completely different ways in the liver. The effects of D-allulose on glucose and fructose levels were negligible in hepatocytes. Erythritol was stable in human and rat hepatocytes (102.1–102.9% remained after 240 min). Intravenous pharmacokinetic studies in rats showed D-allulose was eliminated with a mean half-life of 72.2 min and a systemic clearance of 15.8 mL/min/kg. Taken together, our results indicate that D-allulose is not metabolized in the liver, and thus, unlikely to contribute to hepatic energy production.

scholarly journals Estimating the Oral Absorption from Self-Nanoemulsifying Drug Delivery Systems Using an In Vitro Lipolysis-Permeation Method

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 489
Author(s):  
Mette Klitgaard ◽  
Anette Müllertz ◽  
Ragna Berthelsen
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Aqueous Suspension ◽  
Delivery Systems ◽  
Time Curve ◽  
Drug Permeation ◽  
In Vitro Lipolysis

The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous suspension) from a previously published pharmacokinetic study in rats. In that study, the pharmacokinetic profiles of the five formulations did not correlate with the drug solubilization profiles obtained during in vitro intestinal lipolysis. Using the designed lipolysis-permeation method, in vitro lipolysis of the five formulations was followed by in vitro drug permeation in Franz diffusion cells equipped with PermeaPad® barriers. A linear in vivo–in vitro correlation was obtained when comparing the area under the in vitro drug permeation–time curve (AUC0–3h), to the AUC0–3h of the plasma concentration–time profile obtained from the in vivo study. Based on these results, the evaluated lipolysis-permeation method was found to be a promising tool for estimating the in vivo performance of SNEDDSs, but more studies are needed to evaluate the method further.

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