Effects of Various Absorption Enhancers on the Intestinal Absorption of Water Soluble Drugs by in Vitro Ussing Chamber Method: Correlation with an in Situ Absorption Experiment.

Abstract Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

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Comparison of the intestinal absorption and bioavailability of γ-tocotrienol and α-tocopherol: in vitro, in situ and in vivo studies

Biopharmaceutics & Drug Disposition ◽

10.1002/bdd.1790 ◽

2012 ◽

Vol 33 (5) ◽

pp. 246-256 ◽

Cited By ~ 30

Author(s):

Bilal S. Abuasal ◽

Hisham Qosa ◽

Paul W. Sylvester ◽

Amal Kaddoumi

Keyword(s):

Intestinal Absorption ◽

In Vivo Studies

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Absorption Properties of Luteolin and Apigenin in Genkwa Flos Using In Situ Single-Pass Intestinal Perfusion System in the Rat

The American Journal of Chinese Medicine ◽

10.1142/s0192415x1750094x ◽

2017 ◽

Vol 45 (08) ◽

pp. 1745-1759 ◽

Cited By ~ 6

Author(s):

Xin He ◽

Zi-Jing Song ◽

Cui-Ping Jiang ◽

Chun-Feng Zhang

Keyword(s):

Small Intestine ◽

Intestinal Absorption ◽

Rat Model ◽

Clinical Effectiveness ◽

Intestinal Perfusion ◽

Flower Bud ◽

Transport Pathway ◽

Absorption Enhancers ◽

Single Pass

The flower bud of Daphne genkwa (Genkwa Flos) is a commonly used herbal medicine in Asian countries. Luteolin and apigenin are two recognized active flavonoids in Genkwa Flos. The aim of this study was to investigate the intestinal absorption mechanisms of Genkwa Flos flavonoids using in situ single-pass intestinal perfusion rat model. Using HPLC, we determined its major effective flavonoids luteolin, apigenin, as well as, hydroxygenkwanin and genkwanin in biological samples. The intestinal absorption mechanisms of the total flavonoids in Genkwa Flos (TFG) were investigated using in situ single-pass intestinal perfusion rat model. Comparing the TFG absorption rate in different intestinal segments, data showed that the small intestine absorption was significantly higher than that of the colon ([Formula: see text]). Compared with duodenum and ileum, the jejunum was the best small intestinal site for TFG absorption. The high TFG concentration (61.48[Formula: see text][Formula: see text]g/ml) yielded the highest permeability ([Formula: see text]). Subsequently, three membrane protein inhibitors (verapamil, pantoprazole and probenecid) were used to explore the TFG absorption pathways. Data showed probenecid, a multidrug resistance protein (or MRP) inhibitor, effectively enhanced the TFG absorption ([Formula: see text]). Furthermore, by comparing commonly used natural absorption enhancers on TFG, it was observed that camphor was the most effective. In Situ single-pass intestinal perfusion experiment shows that TFG absorption is much higher in the small intestine than in the colon, and the TFG is absorbed mainly via an active transport pathway with MRP-mediated efflux mechanism. Camphor obviously enhanced the TFG absorption, and this could be an effective TFG formulation preparation method to increase clinical effectiveness after Genkwa Flos administration. Our study elucidated the TFG absorption mechanisms, and provided new information for its formulation preparation.

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A novel zinc complex with antibacterial and antioxidant activity

BMC Chemistry ◽

10.1186/s13065-021-00745-2 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Yun Zhang ◽

Xiaojing Li ◽

Jia Li ◽

Md. Zaved Hossain Khan ◽

Fanyi Ma ◽

...

Keyword(s):

Antibacterial Activity ◽

Acute Toxicity ◽

Intestinal Absorption ◽

Antioxidant Activities ◽

Zinc Ion ◽

Water Soluble ◽

Zinc Supplement ◽

Citrate Complex ◽

Morphology Characterization

Abstract Background In order to enhance the antibacterial activity and reduce the toxicity of Zn2+, novel complexes of Zn(II) were synthesized. Results A water-soluble zinc-glucose-citrate complex (ZnGC) with antibacterial activity was synthesized at pH 6.5. The structure, morphology, characterization, acute toxicity, antibacterial and antioxidant activities, and in situ intestinal absorption were investigated. The results showed that zinc ion was linked with citrate by coordinate bond while the glucose was linked with it through intermolecular hydrogen bonding. The higher the molecular weight of sugar is, the more favorable it is to inhibit the formation of zinc citrate precipitation. Compared with ZnCl2, ZnGC complex presented better antibacterial activity against Staphylococcus aureus (S. aureus, Gram-positive) and Escherichia coli (E. coli, Gram-negative). Conclusions The results of acute toxicity showed no obvious toxicity in this test and in situ intestinal absorption study, suggesting that ZnGC complex could be used as a potential zinc supplement for zinc deficiency.

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Mechanistic Studies on the Absorption-Enhancing Effects of Gemini Surfactant on the Intestinal Absorption of Poorly Absorbed Hydrophilic Drugs in Rats

Pharmaceutics ◽

10.3390/pharmaceutics11040170 ◽

2019 ◽

Vol 11 (4) ◽

pp. 170 ◽

Cited By ~ 3

Author(s):

Tammam Alama ◽

Kosuke Kusamori ◽

Masaki Morishita ◽

Hidemasa Katsumi ◽

Toshiyasu Sakane ◽

...

Keyword(s):

Intestinal Absorption ◽

Gemini Surfactant ◽

Closed Loop ◽

Intestinal Cell ◽

Mechanistic Studies ◽

High Potency ◽

Absorption Enhancers ◽

Hydrophilic Drugs ◽

Loop Method

Generally, the use of absorption enhancers might be the most effective approaches to ameliorate the enteric absorption of poorly absorbed substances. Among numerous absorption enhancers, we already reported that a gemini surfactant, sodium dilauramidoglutamide lysine (SLG-30) with two hydrophobic and two hydrophilic moieties, is a novel and promising adjuvant with a high potency in improving the absorption safely. Here, we examined and elucidated the absorption-improving mechanisms of SLG-30 in the enteric absorption of substances. SLG-30 increased the intestinal absorption of 5(6)-carboxyfluorescein (CF) to a greater level than the typical absorption enhancers, including sodium glycocholate and sodium laurate, as evaluated by an in situ closed-loop method. Furthermore, SLG-30 significantly lowered the fluorescence anisotropy of dansyl chloride (DNS-Cl), suggesting that it might increase the fluidity of protein sections in the intestinal cell membranes. Moreover, SLG-30 significantly lowered the transepithelial-electrical resistance (TEER) values of Caco-2 cells, suggesting that it might open the tight junctions (TJs) between the enteric epithelial cells. Additionally, the levels of claudin-1 and claudin-4 expression decreased in the presence of SLG-30. These outcomes propose that SLG-30 might improve the enteric transport of poorly absorbed substances through both transcellular and paracellular routes.

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Enhancing the Oral Bioavailability of Candesartan Cilexetil Loaded Nanostructured Lipid Carriers: In Vitro Characterization and Absorption in Rats after Oral Administration

Pharmaceutics ◽

10.3390/pharmaceutics12111047 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1047

Author(s):

Walid Anwar ◽

Hamdy Dawaba ◽

Mohsen Afouna ◽

Ahmed Samy ◽

Mohammed Rashed ◽

...

Keyword(s):

Oral Bioavailability ◽

Candesartan Cilexetil ◽

Aqueous Solubility ◽

Systemic Circulation ◽

Nanostructured Lipid Carriers ◽

Water Soluble ◽

Nanostructured Lipid Carrier ◽

In Vitro Characterization ◽

Water Soluble Drugs

Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.

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