scholarly journals Influence of fatty acid patterns on the intestinal absorption pathway of quercetin in thoracic lymph duct-cannulated rats

2012 ◽  
Vol 109 (12) ◽  
pp. 2147-2153 ◽  
Author(s):  
Kaeko Murota ◽  
Rainer Cermak ◽  
Junji Terao ◽  
Siegfried Wolffram
Keyword(s):  
Fatty Acids ◽  
Dietary Fats ◽  
Lymphatic Transport ◽  
First Pass Metabolism ◽  
First Pass ◽  
Lymph Duct ◽  
Fatty Acid Patterns ◽  
Pass Metabolism ◽  
Plasma Concentration Curve ◽  
Chain Fatty Acids

Since it is known that dietary fats improve the bioavailability of the flavonol quercetin, we purposed to investigate whether this effect is due to increased lymphatic transport of quercetin. In rats with implanted catheters in the thoracic lymph duct, we administered quercetin into the duodenum with TAG emulsions containing either long-chain fatty acids (LCT) or medium-chain fatty acids (MCT). Controls received quercetin together with a glucose solution. LCT administration increased the lymphatic output of quercetin (19·1 (sem1·2) nmol/8 h) as well as the lymph-independent bioavailability of the flavonol, determined as area under the plasma concentration curve (1091 (sem142) μm× min). Compared with glucose administration, MCT neither increased the lymphatic output (12·3 (sem1·5) nmol/8 h) nor the bioavailability of quercetin (772 (sem99) μm× min) significantly (glucose group: 9·8 (sem1·5) nmol/8 h and 513 (sem55) μm× min, respectively). Because LCT are released within chylomicrons into the intestinal lymph while MCT are mainly released into the portal blood, we conclude from the present results that dietary fats that are mainly composed of LCT improve quercetin bioavailability by increasing its transport via the lymph, thereby circumventing hepatic first-pass metabolism of the flavonol. In addition, LCT could enhance quercetin absorption by improving its solubility in the intestinal tract.

scholarly journals Quality by Design Approach for Development and Characterisation of Solid Lipid Nanoparticles of Quetiapine Fumarate

2020 ◽  
Vol 16 (1) ◽  
pp. 73-91 ◽  
Author(s):  
Shweta Agarwal ◽  
Rayasa S. Ramachandra Murthy ◽  
Sasidharan Leelakumari Harikumar ◽  
Rajeev Garg
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Quality By Design ◽  
Lipid Nanoparticles ◽  
Lymphatic Transport ◽  
Quetiapine Fumarate ◽  
Solid Lipid ◽  
First Pass Metabolism ◽  
First Pass ◽  
Quality By Design Approach ◽  
Pass Metabolism

Background: Quetiapine fumarate, a 2nd generation anti-psychotic drug has oral bioavailability of 9% because of hepatic first pass metabolism. Reports suggest that co-administration of drugs with lipids affects their absorption pathways, enhances lymphatic transport thus bypassing hepatic first-pass metabolism resulting in enhanced bioavailability. Objective: The present work aimed at developing, and characterising potentially lymphatic absorbable Solid Lipid Nanoparticles (SLN) of quetiapine fumarate by Quality by Design approach. Method: Hot emulsification followed by ultrasonication was used as a method of preparation. Precirol ATO5, Phospholipon 90G and Poloxamer 188 were used as a lipid, stabilizer and surfactant respectively. A32 Central Composite design optimised the 2 independent variables, lipid concentration and stabilizer concentration and assessed their effect on percent Entrapment Efficiency (%EE: Y1). The lyophilized SLNs were studied for stability at 5 ±3οC and 25 ± 2οC/60 ± 5% RH for 3 months. Results: The optimised formula derived for SLN had 270mg Precirol ATO5 and 107mg of Phospholipon 90G giving %EE of 76.53%. Mean particle size was 159.8nm with polydispersity index 0.273 and zeta potential -6.6mV. In-vitro drug release followed Korsmeyer-Peppas kinetics (R2=0.917) with release exponent n=0.722 indicating non-Fickian diffusion. Transmission electron microscopy images exhibited particles to be spherical and smooth. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction studies ascertained drug-excipient compatibility. Stability studies suggested 5οC as appropriate temperature for storage and preserving important characteristics within acceptable limits. Conclusion: Development and optimisation by Quality by Design were justified as it yielded SLN having acceptable characteristics and potential application for intestinal lymphatic transport.

The prospects of lipidic prodrugs: an old approach with an emerging future

2019 ◽  
Vol 11 (19) ◽  
pp. 2563-2571 ◽  
Author(s):  
Arik Dahan ◽  
Milica Markovic ◽  
Aaron Aponick ◽  
Ellen M Zimmermann ◽  
Shimon Ben-Shabat
Keyword(s):  
Metabolic Pathways ◽  
Drug Targeting ◽  
Unmet Needs ◽  
Pharmacokinetic Profile ◽  
Lymphatic Transport ◽  
First Pass Metabolism ◽  
First Pass ◽  
Clinical Benefits ◽  
Physiological Pathways ◽  
Pass Metabolism

Nowadays, prodrugs are no longer used as a last resort, rather, they are intentionally designed at the early stages of drug development. Lipidic prodrug strategy, where a drug moiety is covalently bound to a lipid carrier, was initially proposed half a century ago, yet, this approach still remains to be explored. Lipidic prodrugs can join physiological lipid metabolic pathways, and hence provide drug targeting via lymphatic transport or site-specific drug release, improve drugs’ pharmacokinetic profile, overcome obstacles originating from biological barriers and bypass hepatic first-pass metabolism. Physiological pathways of lipid processing, uses of different lipidic prodrugs and their clinical benefits are overviewed. Overall, lipidic prodrugs present a promising approach for overcoming different obstacles and fulfilling various unmet needs in drug delivery/targeting.

Intestinal Lymphatic Transport Enhances the Post-Prandial Oral Bioavailability of a Novel Cannabinoid Receptor Agonist Via Avoidance of First-Pass Metabolism

2009 ◽  
Vol 26 (6) ◽  
pp. 1486-1495 ◽  
Author(s):  
Natalie L. Trevaskis ◽  
David M. Shackleford ◽  
William N. Charman ◽  
Glenn A. Edwards ◽  
Anne Gardin ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Receptor Agonist ◽  
Cannabinoid Receptor ◽  
Lymphatic Transport ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

scholarly journals Glyceride-Mimetic Prodrugs Incorporating Self-Immolative Spacers Promote Lymphatic Transport, Avoid First-Pass Metabolism, and Enhance Oral Bioavailability

2016 ◽  
Vol 128 (44) ◽  
pp. 13904-13909 ◽  
Author(s):  
Luojuan Hu ◽  
Tim Quach ◽  
Sifei Han ◽  
Shea F. Lim ◽  
Preeti Yadav ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Lymphatic Transport ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Identification of a Cranberry Juice Product Capable of Inhibiting Enteric CYP3A-Mediated First-Pass Metabolism in Humans

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
N Ngo ◽  
Z Yan ◽  
TN Graf ◽  
DR Carrizosa ◽  
EC Dees ◽  
...  
Keyword(s):  
Cranberry Juice ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Development, Characterization and Optimization of Mucoadhesive Tablet for Buccal Delivery of Domperidone

2019 ◽  
Vol 9 (1) ◽  
pp. 37-49
Author(s):  
Jagdale Sachin ◽  
Panbude Aishwarya ◽  
Navasare Priya
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Research Work ◽  
Wet Granulation ◽  
Buccal Delivery ◽  
Scanning Calorimetry ◽  
Mucoadhesive Polymers ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. </P><P> Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). </P><P> Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

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