Competitive displacement of drugs from cyclodextrin inclusion complex by polypseudorotaxane formation with poloxamer: Implications in drug solubilization and delivery

Nogueiras-Nieto, Luis; Sobarzo‐Sánchez, Eduardo; Gómez-Amoza, J.L.; Otero-Espinar, Francisco J.

doi:10.1016/j.ejpb.2011.12.001

Cited by 46 publications

(32 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When used above 0.1%, TPGS might have competed with the drug for CD cavity and the free TPGS and CD molecules available for drug molecules could have been insufficient to solubilize the drug efficiently and eventually caused decrease in drug solubility. Such phenomenon of competition in the presence of surfactant excipients has already been reported [12]. Even if TPGS had not competed for CD cavity, there could have been some interaction between TPGS and the external surface of HPBCD which would have interfered with the drug affinity to the inner cavity of CD.…”

Section: Discussionmentioning

confidence: 93%

“…While HPBCD is also known to cause non-inclusion type of micellization/self-association mode of solubilization of drugs, the surfactant activity of TPGS is likely to prevent the former possibility. Surfactant excipients, when used as ternary components, are known to prevent the formation of HPBCD aggregates [12]. TPGS could have completely coated the E-CD inclusion complex (indicated by SEM studies) by interacting with both the drug and CD by weak intermolecular bonds and formed a stable E-CD-TPGS ternary system.…”

Section: Discussionmentioning

confidence: 99%

“…However, with the concentration of TPGS kept optimum in the solid ternary system (0.05%), we assumed that the competition phenomenon subsided. Both CD and TPGS could have been available to the drug as solubilizers by inclusion complexation and by surfactant (micellar solubilization) effect, respectively [12]. While HPBCD is also known to cause non-inclusion type of micellization/self-association mode of solubilization of drugs, the surfactant activity of TPGS is likely to prevent the former possibility.…”

Section: Discussionmentioning

confidence: 99%

“…The ternary systems may further improve the physicochemical and transport properties of drugs in comparison to binary complexes [8]. Literature reports several studies on the effect of water-soluble substances like polymers [9][10][11], surfactants [12], metal salts [13], and amino acids [14] on CD solubilization of drugs. In the present study, we evaluated the effect of two hydrophilic auxiliary substances, namely, D-α-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS or simply TPGS) and L-ascorbic acid-2-glucoside (AA2G), as third components to the CD complexes, for the first time.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improved Aqueous Solubility and Antihypercholesterolemic Activity of Ezetimibe on Formulating with Hydroxypropyl-β-Cyclodextrin and Hydrophilic Auxiliary Substances

Srivalli

Mishra

2015

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The purpose of this study was to improve the aqueous solubility, dissolution, and pharmacodynamic properties of a BCS class II drug, ezetimibe (Eze) by preparing ternary cyclodextrin complex systems. We investigated the potential synergistic effect of two novel hydrophilic auxiliary substances, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and L-ascorbic acid-2-glucoside (AA2G) on hydroxypropyl-β-cyclodextrin (HPBCD) solubilization of poorly water-soluble hypocholesterolemic drug, Eze. In solution state, the binary and ternary systems were analyzed by phase solubility studies and Job's plot. The solid complexes prepared by freeze-drying were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and scanning electron microscopy (SEM). The log P values, aqueous solubility, dissolution, and antihypercholesterolemic activity of all systems were studied. The analytical techniques confirmed the formation of inclusion complexes in the binary and ternary systems. HPBCD complexation significantly (p<0.05) reduced the log P and improved the solubility, dissolution, and hypocholesterolemic properties of Eze, and the addition of ternary component produced further significant improvement (p<0.05) even compared to binary system. The remarkable reduction in log P and enhancement in solubility, dissolution, and antihypercholesterolemic activity due to the addition of TPGS or AA2G may be attributed to enhanced wetting, dispersibility, and complete amorphization. The use of TPGS or AA2G as ternary hydrophilic auxiliary substances improved the HPBCD solubilization and antihypercholesterolemic activity of Eze.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improved Aqueous Solubility and Antihypercholesterolemic Activity of Ezetimibe on Formulating with Hydroxypropyl-β-Cyclodextrin and Hydrophilic Auxiliary Substances

Srivalli

Mishra

2015

AAPS PharmSciTech

View full text Add to dashboard Cite

show abstract

“…NMR analysis has been previously utilized to study the complexation between drugs and polymers 33 . Chloroform was used as the solvent in this study.…”

Section: H Nmr Analysis Of Cpm-eudragit õ Fs Precipitatementioning

confidence: 99%

Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS

Zhang

2015

Drug Development and Industrial Pharmacy

View full text Add to dashboard Cite

The objective of this research project was to characterize the drug release profiles, physicochemical properties and drug-polymer interaction of melt-extruded granules consisting of chlorpheniramine maleate (CPM) and Eudragit® FS. Melt extrusion was performed using a single screw extruder at a processing temperature of 65-75 °C. The melt extrudate was milled, blended with lactose monohydrate and then filled into hard gelatin capsules. Each capsule contained 300 mg CPM granules. The release of CPM was determined with the United States Pharmacopeia dissolution apparatus II using a three-stage dissolution medium testing in order to simulate the pH conditions of the gastrointestinal tract. Pore structure, thermal properties and surface morphologies of CPM granules were studied using mercury and helium pycnometer, differential scanning calorimeter and scanning electron microscope. Sustained release of CPM over 10 h was achieved. The release of CPM was a function of drug loading and the size of the milled granules. The complexation between CPM and Eudragit® FS as the result of counterion condensation was observed, and the interaction was characterized using membrane dialysis and H(1) NMR techniques. In both 0.1 N HCl and phosphate buffer pH 6.8, CPM was released via a diffusion mechanism and the release rate was controlled by the pore structure of the melt-extruded granules. In phosphate buffer pH 7.4, CPM release was controlled by the low pH micro-environment created by CPM, the pore structure of the granules and the in situ complexation between CPM and Eudragit® FS.

show abstract

Preparation, binding behaviours and thermal stability of inclusion complexes between (Z)‐jasmone and acyclic cucurbit[n]urils

Yin

Zhang

Liu

et al. 2022

Flavour & Fragrance J

View full text Add to dashboard Cite

Z)-jasmone is the most important contribution to the scents of perfumes and cosmetics. However, (Z)-jasmone is water insoluble and highly volatile, which limits its development and application. Inclusion technology has become a promising strategy to improve the solubility and stability of hydrophobic small molecules. Here, we used saturated aqueous solution and freeze-drying method to prepare solid inclusion complexes of (Z)-jasmone and three acyclic cucurbit[n]urils (ACBs, M1-M3), and studied their binding behaviours by fluorescence spectroscopy, NMR, XRD, FT-IR, TG and DSC, confirming the formation of the host-guest inclusion complexes. The stoichiometry of inclusion complexes was 1:1 by Job's plot. The inclusion complexes exhibited better water solubility, higher thermal stability and heat-controlled release comparing with that of native (Z)-jasmone. This work uncloses a new strategy to enhance the performance of essential oil and flavours/fragrances and further application in the field of cosmetic and food industry.

show abstract

Competitive displacement of drugs from cyclodextrin inclusion complex by polypseudorotaxane formation with poloxamer: Implications in drug solubilization and delivery

Cited by 46 publications

References 34 publications

Improved Aqueous Solubility and Antihypercholesterolemic Activity of Ezetimibe on Formulating with Hydroxypropyl-β-Cyclodextrin and Hydrophilic Auxiliary Substances

Improved Aqueous Solubility and Antihypercholesterolemic Activity of Ezetimibe on Formulating with Hydroxypropyl-β-Cyclodextrin and Hydrophilic Auxiliary Substances

Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS

Preparation, binding behaviours and thermal stability of inclusion complexes between (Z)‐jasmone and acyclic cucurbit[n]urils

Contact Info

Product

Resources

About