Binding Specificity between Small Organic Solutes in Aqueous Solution: Classification of Some Solutes into Two Groups According to Binding Tendencies

Higuchi, Takeru; Kristiansen, Heidi

doi:10.1002/jps.2600591112

Cited by 105 publications

(41 citation statements)

References 19 publications

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“…These results demonstrated the formation of 1:1 complex at lower CD concentration and 1:n complex at higher CD concentration, which was similar to the inclusion process of previous complexes of CDs with azole antifungal agents (24,25). Thus, the upward curvatures were quantitatively analyzed according to the optimization technique to obtain the stability constants of higher order complex (K 1:n ) (26).…”

Section: Phase Solubility Studiessupporting

confidence: 71%

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

Tang

Wang²,

et al. 2016

AAPS PharmSciTech

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Abstract. Posaconazole is a triazole antifungal drug that with extremely poor aqueous solubility. Up to now, this drug can be administered via intravenous injection and oral suspension. However, its oral bioavailability is greatly limited by the dissolution rate of the drug. This study aimed to improve water solubility and dissolution of posaconazole through characterizing the inclusion complexes of posaconazole with β-cyclodextrin (β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD). Phase solubility studies were performed to calculate the stability constants in solution. The results of FT-IR, PXRD, 1 H and ROESY 2D NMR, and DSC all verified the formation of the complexes in solid state. The complexes showed remarkably improved water solubility and dissolution rate than pure posaconazole. Especially, the aqueous solubility of the DM-β-CD complex is nine times higher than that of the β-CD complex. Preliminary in vitro antifungal susceptibility tests showed that the two inclusion complexes maintained high antifungal activities. These results indicated that the DM-β-CD complexes have great potential for application in the delivery of poorly water-soluble antifungal agents, such as posaconazole.

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Section: Phase Solubility Studiessupporting

confidence: 71%

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

Tang

Wang²,

et al. 2016

AAPS PharmSciTech

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“…On the other hand, the positively deviated diagrams were analyzed by the previously reported equations that are derived on the basis of the consecutive inclusion equilibrium, using a non-linear least-squares method (MULTI program) coupled with the iterative method, to obtain the K 1 : 1 and K 1 : 2 (guest : host) stability constants. 18,19) The curve fitting was evaluated with a reference of Akaike's Information Criterion (AIC, the smaller AIC value means the better fit), 20) and were Ϫ180-Ϫ200. The solubility of FPFS-410 at acidic regions (pH Ͻ5) was too low to measure accurately using HPLC (pK a of FPFS-410: 3.4).…”

mentioning

confidence: 99%

Improvement of Solubility and Oral Bioavailability of 2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) with Antidiabetic and Lipid-Lowering Activities in Dogs by 2-Hydroxypropyl-.BETA.-cyclodextrin

Hara

Hirayama

Arima

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Diabetes mellitus is classified into two groups, non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Since insulin resistance has been acquired in NIDDM patients, insulin, its analogues and sulfonylureas cannot lower serum glucose levels sufficiently. In addition, insulin resistance contributes to the hyperglycemic state in about 80-85% of patients with this disorder.1,2) Complication of diabetes mellitus and hyperlipidemia is associated with increasing the risk of atherosclerosis. Thiazolidinedione class of drugs (TZDs), such as rosiglitazone and pioglitazone, are new type of antidiabetic agents. TZDs significantly reduce fasting plasma glucose levels by improving insulin sensitivity in NIDDM patients.3,4) Furthermore, TZDs were reported to improve lipid metabolism in NIDDM patients. 5,6) TZDs are reported to influence several processes that increase cell sensitivity to insulin, 7,8) including activation of peroxisome proliferator-activated receptor g (PPARg), 9,10) although their mechanism has not been fully elucidated. TZDs are widely used in clinical practice, but in some cases they cause weight gain, plasma volume expansion, edema or hepatotoxicity.11,12) Because these unwelcome effects of TZDs are supposed to be due to activation of PPARg, various intensive attempts have been conducted to search drug candidates with potent antidiabetic and lipidlowering activities, but with low affinity to PPARg.2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) (Fig. 1, molecular weight 331.4), a newly synthesized cyanoimino-oxothiazolidine with improving insulin sensitivity, has shown potent lowering effects on serum glucose and triglyceride at the preclinical stage. Furthermore, FPFS-410 has much less potency for PPARg activation compared with pioglitazone and does not cause body weight gain in rodents.13) Despite these valuable features, FPFS-410 exhibits an extremely low aqueous solubility (2.8 (Ϯ0.33)ϫ10Ϫ8 M (0.0094Ϯ0.0011 mg/ml) in 1.0 M phosphate buffer (pH 7.0) at 25°C), which is a drawback for its practical use.Cyclodextrins (CyDs) are cyclic oligosaccharides consisting of usually six, seven, or eight glucose units (a-, b-, gCyDs, respectively) bound by 1,4-glycosidic linkages. CyDs form inclusion complexes with lipophilic drugs and improve their water solubility, dissolution rate and bioavailability.14-16) However, the solubilization effect of CyDs on drugs is dependent on the interaction strength between guest and host molecules, i.e., cavity size of CyDs, spatial fitness of guest/host molecules, stoichiometry of complex, hydrophobicity of guest molecule, etc. Therefore, when a drug is to be formulated as CyD complex, it is important to select the most suitable CyD for the drug. Recently, various kinds of b-CyD derivatives have been developed to enhance the inclusion property and solubility of parent b-CyD and to improve pharmaceutical properties of drugs through the CyD Improvement of Solubility and Oral Bioavailability of 2-(N-Cyanoimino)-5-...

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“…The apparent stability constant of inclusion complex (K c ) was calculated from the phase solubility diagrams using the following equation (Eq. (1)) when the stoichiometry of the inclusion complex is 1:1 [13]: Here, the slope is determined from the initial straight-line portion of the plot of a-tocopherol solubility against host concentrations, and S 0 is the intrinsic solubility. The concentration range of each host molecule was selected low concentration range, assuming 1:1 inclusion complex formation (HPG-bCD: 0.86e8.57 mM, HPG: 1.67e16.7 mM, and HP-bCD: 0.73e7.25 mM).…”

Section: Resultsmentioning

confidence: 99%

Enhanced solubilization of α-tocopherol by hyperbranched polyglycerol-modified β-cyclodextin

Kimura

Ooya

2016

Journal of Drug Delivery Science and Technology

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Binding Specificity between Small Organic Solutes in Aqueous Solution: Classification of Some Solutes into Two Groups According to Binding Tendencies

Cited by 105 publications

References 19 publications

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

Improvement of Solubility and Oral Bioavailability of 2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) with Antidiabetic and Lipid-Lowering Activities in Dogs by 2-Hydroxypropyl-.BETA.-cyclodextrin

Enhanced solubilization of α-tocopherol by hyperbranched polyglycerol-modified β-cyclodextin

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