Ketoconazole: Solving the Poor Solubility via Cocrystal Formation with Phenolic Acids

2020 ◽  
Vol 20 (10) ◽  
pp. 6973-6982
Author(s):  
Xin Chen ◽  
Duanxiu Li ◽  
Zongwu Deng ◽  
Hailu Zhang
Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 175
Author(s):  
Dong-Gyun Han ◽  
Eunju Cha ◽  
Jeongmin Joo ◽  
Ji Sun Hwang ◽  
Sanghyun Kim ◽  
...  

Acacetin, an important ingredient of acacia honey and a component of several medicinal plants, exhibits therapeutic effects such as antioxidative, anticancer, anti-inflammatory, and anti-plasmodial activities. However, to date, studies reporting a systematic investigation of the in vivo fate of orally administered acacetin are limited. Moreover, the in vitro physicochemical and biopharmaceutical properties of acacetin in the gastrointestinal (GI) tract and their pharmacokinetic impacts remain unclear. Therefore, in this study, we aimed to systematically investigate the oral absorption and disposition of acacetin using relevant rat models. Acacetin exhibited poor solubility (≤119 ng/mL) and relatively low stability (27.5–62.0% remaining after 24 h) in pH 7 phosphate buffer and simulated GI fluids. A major portion (97.1%) of the initially injected acacetin dose remained unabsorbed in the jejunal segments, and the oral bioavailability of acacetin was very low at 2.34%. The systemic metabolism of acacetin occurred ubiquitously in various tissues (particularly in the liver, where it occurred most extensively), resulting in very high total plasma clearance of 199 ± 36 mL/min/kg. Collectively, the poor oral bioavailability of acacetin could be attributed mainly to its poor solubility and low GI luminal stability.


2021 ◽  
Vol 5 (1) ◽  
pp. 2
Author(s):  
Nuno F. da Costa ◽  
João F. Pinto ◽  
Ana I. Fernandes

The evaluation of the processability of co-amorphous mixtures is of paramount importance since these systems are increasingly used to address the poor solubility presented by most of the drugs in research and development. This work shows that co-amorphous olanzapine powders present higher cohesiveness than their crystalline counterpart and resulted in the production of tablets with a higher tensile strength and a slower release of the drug. As a result, this work demonstrates that despite the solubility advantages of co-amorphous mixtures, consideration should be given to the downstream processing of formulations containing such materials.


2001 ◽  
Vol 79 (11) ◽  
pp. 1799-1805 ◽  
Author(s):  
Xiao-Xiang Zhang ◽  
Michele C Harris ◽  
Joseph P Sadighi ◽  
Stephen L Buchwald

The use of palladium chloride as a precatalyst for the amination of aryl bromides is reported. To overcome the poor solubility of palladium chloride in commonly used solvents, a procedure was developed in which PdCl2 was preheated with neat amine in the presence of a phosphine ligand before the addition of the other reaction components. This protocol is effective for a broad range of substrate combinations using several types of phosphine ligands.Key words: palladium chloride, amination, aryl bromide, phosphine ligand.


Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6274
Author(s):  
Jiumn-Yih Wu ◽  
Tzi-Yuan Wang ◽  
Hsiou-Yu Ding ◽  
Yun-Rong Zhang ◽  
Shu-Yuan Lin ◽  
...  

Vitexin is a C-glucoside flavone that exhibits a wide range of pharmaceutical activities. However, the poor solubility of vitexin limits its applications. To resolve this limitation, two glycoside hydrolases (GHs) and four glycosyltransferases (GTs) were assayed for glycosylation activity toward vitexin. The results showed that BtGT_16345 from the Bacillus thuringiensis GA A07 strain possessed the highest glycosylation activity, catalyzing the conversion of vitexin into new compounds, vitexin-4′-O-β-glucoside (1) and vitexin-5-O-β-glucoside (2), which showed greater aqueous solubility than vitexin. To our knowledge, this is the first report of vitexin glycosylation. Based on the multiple bioactivities of vitexin, the two highly soluble vitexin derivatives might have high potential for pharmacological usage in the future.


CrystEngComm ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. 800-806 ◽  
Author(s):  
Mohsin R. Arabiani ◽  
Anurag Lodagekar ◽  
Balvant Yadav ◽  
Rahul B. Chavan ◽  
Nalini R. Shastri ◽  
...  

In the present study, cocrystallization of a new piprazole analogue drug, brexpiprazole (BREX), with coformers such as succinic acid and catechol was carried out using ball milling to address the poor solubility and dissolution rate of the molecule.


2020 ◽  
Vol 27 (40) ◽  
pp. 6849-6863 ◽  
Author(s):  
Majid Rezayi ◽  
Pegah Mahmoodi ◽  
Hadis Langari ◽  
Behzad Behnam ◽  
Amirhossein Sahebkar

In the last decade, the use of carbon nanotubes and graphenes has been on the rise for various nanobiotechnological applications. Owing to their special characteristics, these two nanostructures of carbon allotropes have been studied for their capacity in the detection and treatment of many diseases. On the other hand, curcumin, a well-known antioxidant and anticancer natural product, is being extensively studied for numerous medicinal applications. Interestingly, many reports have shown great potentials of conjugates of curcumin and carbon nanotubes or graphenes. These conjugates, when properly designed and functionalized with biomolecules, could represent the valuable properties of each component alone while they could be effective in overcoming the poor solubility issues of both curcumin and Carbon Nanomaterials (CNMs). In this case, curcumin conjugates with CNMs seem to be very promising in biosensing applications and the detection of many biomolecules, especially, curcumin has been reported to be very effective with these conjugates. Also, the delivery of curcumin using functionalized SWCNTs was evaluated for its ability to load and release curcumin, to protect curcumin from degradation and to enhance its solubility. It is proposed that other properties of these conjugates are still to be discovered and the interdisciplinary approaches among biology, medicine, chemistry, and material engineering will accelerate the applications of these novel materials. This review aims to summarize the findings on the applications of CNM conjugates of curcumin.


Fermentation ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 232
Author(s):  
Chien-Min Chiang ◽  
Tzi-Yuan Wang ◽  
Jiumn-Yih Wu ◽  
Yun-Rong Zhang ◽  
Shu-Yuan Lin ◽  
...  

8-Hydroxydaidzein (8-OHDe) is a non-natural isoflavone polyphenol isolated from fermented soybean foods. 8-OHDe exhibits a wide range of pharmaceutical activities. However, both the poor solubility and instability of 8-OHDe limit its applications. To resolve the limitations of 8-OHDe, Deinococcus geothermalis amylosucrase (DgAS) has previously been used to glycosylate 8-OHDe to produce soluble and stable 8-OHDe-7-O-α-glucopyranoside (8-OHDe-7-G) in a 0.5 h reaction time. In this study, we aimed to use DgAS and an extended reaction time to produce 8-OHDe diglucosides. At least three 8-OHDe derivatives were produced after a 24 h reaction time, and two major products were successfully purified and identified as new compounds: 8-OHDe-7-O-[α-glucopyranosyl-(1®6)-α-glucopyranoside] (8-OHDe-7-G2) and 8-OHDe-7,4′-O-α-diglucopyranoside (8-OHDe-7-G-4′-G). 8-OHDe-7-G-4′-G showed a 4619-fold greater aqueous solubility than 8-OHDe. In addition, over 92% of the 8-OHDe diglucosides were stable after 96 h, while only 10% of the 8-OHDe could be detected after being subjected to the same conditions. The two stable 8-OHDe diglucoside derivatives have the potential for pharmacological usage in the future.


2013 ◽  
Vol 10 (1) ◽  
pp. 14 ◽  
Author(s):  
Nicholas C Obitte ◽  
Lisa C Rohan ◽  
Christianah M Adeyeye ◽  
Michael A Parniak ◽  
Charles O Esimone

2021 ◽  
Author(s):  
Tianzhu Guan ◽  
Guangjie Zhang ◽  
Yantong Sun ◽  
Jie Zhang ◽  
Li Ren

The active compounds in star anise alcohol extractives (SAAE) have the potent bioactivity. However, the poor solubility and stability limit their applications. In this study, SAAE/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex were...


2013 ◽  
Vol 292 (2) ◽  
pp. 477-484 ◽  
Author(s):  
Xiaoping Chen ◽  
Pengzhan Fei ◽  
Kevin A. Cavicchi ◽  
Wenwen Yang ◽  
Neil Ayres

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