Enhancement of Drug Solubility in Supramolecular and Colloidal Systems

Süle, András; Szente, Lajos; Csempesz, Ferenc

doi:10.1002/jps.21437

Cited by 18 publications

(13 citation statements)

References 26 publications

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“…Such a complex formation notably accelerates the hydrolysis of the ring (Table 2). 33 As previous observed at pH 6.5,32 αCD showed a relatively low ability to solubilize simvastatin at pH 7.4 (Table 2). At the highest αCD concentration tested (9.7%) the amount of simvastatin dissolved increased five‐fold.…”

Section: Resultssupporting

confidence: 80%

“…Thus, the ability of αCD and T908 separately to solubilize simvastatin was evaluated at this pH. It has been previously shown that simvastatin can form inclusion complexes with the natural cyclodextrins and also with synthetic derivatives such as hydroxypropyl‐β‐cyclodextrin with a 1:1 stoichiometry,32 remaining the lactone ring outside the cyclodextrin. Such a complex formation notably accelerates the hydrolysis of the ring (Table 2).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Poloxamine–Cyclodextrin–Simvastatin Supramolecular Systems Promote Osteoblast Differentiation of Mesenchymal Stem Cells

Simões

Veiga

Torres‐Labandeira

et al. 2013

Macromolecular Bioscience

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Osteogenic/osteoinductive systems combine simvastatin, poloxamine Tetronic 908 (T908) and α-cyclodextrins (αCDs) in a supramolecular network that enhances the solubility/stability of the simvastatin hydroxy acid form and synergistically promotes osteoblast differentiation. Incorporation of 5% αCD transforms dilute T908 solutions (as low as 2% copolymer) into gels, enhances the osteoinductive activity of T908, and provides simvastatin sustained release for more than one week, which results in higher and more prolonged alkaline phosphatase (ALP) activity. The performance of the intrinsically osteoinductive polypseudorotaxane scaffold can be easily tuned by modifying the concentrations of T908, αCD, and simvastatin in a certain range of values. Moreover, the use of affordable, stable materials that can be sterilized applying a conventional method make the supramolecular gels advantageous candidates as scaffolds to be applied in the critical defect using minimally invasive techniques.

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Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Poloxamine–Cyclodextrin–Simvastatin Supramolecular Systems Promote Osteoblast Differentiation of Mesenchymal Stem Cells

Simões

Veiga

Torres‐Labandeira

et al. 2013

Macromolecular Bioscience

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“…This can be probably attributed to the complexation of the drug into the DMbCD hydrophobic cavity. The above results also indicate that the carbonyl group of lactone ring of simvastatin might be involved in the complexation process (27).…”

Section: Confirmation Of Simvastatin/ Dmbcd Complexmentioning

confidence: 59%

Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats

Ning

Fan

et al. 2018

Acta Pharmaceutica

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Simvastatin is poorly bioavailable because it is practically insoluble in water and shows dissolution rate-limited absorption. Solubilizing effects of several β-cyclodextrin (βCD) derivatives such as HPβCD, SBEβCD and DMβCD on simvastatin in aqueous solution were investigated using the phase solubility technique. The solubility diagram of simvastatin with each βCD derivative could be classified as AL-type, indicating soluble complex formation of 1:1 stoichiometry. Among the above βCD derivatives DMβCD was found to be the ideal complexing agent for improving drug solubility. The simvastatin complex with DMβCD was prepared using the co-evaporation method and was then characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and in vitro dissolution. Dissolution and pharmacokinetic studies indicated that the simvastatin/DMβCD complex exhibited an increased dissolution rate, rapid absorption, and improved bioavailability in rats compared to free drug. Maximum plasma concentration (cmax) and the time to reach it (tmax) were 21.86 μg mL-1 and 1.4 h for the drug complex, 8.25 μg mL-1 and 3.0 h for free drug, respectively. Main pharmacokinetic parameters such as tmax, cmax were significantly different (p < 0.01) between the simvastatin complex and free drug. Bioavailability of the simvastatin complex relative to free drug was up to 167.0 %.

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“…Several approaches were investigated to enhance the rate of dissolution of lovastatin and/or improve bioavailability. These include: preparation of amorphous lovastatin using freeze drying; inclusion complexes with β‐cyclodextrin (β‐CD) in the absence and the presence of a dissolved polymer or its monomeric compound; solid dispersions using different polymers and superdisintegrants; a sustained release gastroretentive drug delivery system based on floating microspheres using various polymers and their blends; a bilayer regioselective floating tablets of atenolol and lovastatin to give immediate release of lovastatin and sustained release of atenolol; A microemulsion formulation; Nanocrystals prepared using simple precipitation method without using stabilizers or surfactants; Nanostructured lipid carriers (NLCs); and solid lipid nanoparticles (SLNs) prepared by hot homogenization followed by ultrasonication …”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of lovastatin polymeric microparticles by coacervation‐phase separation method for dissolution enhancement

Al-Nimry

Khanfar

2015

J of Applied Polymer Sci

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Dissolution rate of lovastatin is slow, only 30% of the oral dose is absorbed, and it undergoes extensive first-pass extraction resulting in low and variable bioavailability. The objective of this research was to enhance the dissolution rate through preparing polymeric microparticles. Coacervation-phase separation method through the addition of a non-solvent was used to prepare polymeric microparticles. The method was optimized through studying effects of the type of solvent, the type of polymer, drug : polymer ratio and concentration of surfactant on particle size, particle size distribution, and in-vitro drug release. Optimized polymeric microparticles and unprocessed drug were characterized using different techniques (SEM, FTIR, DSC, and PXRD) and their flow properties were evaluated. The optimum microparticles were prepared using ethanol as a solvent, Eudragit V R L 100 as a polymer in a drug:polymer ratio of 1:2 and SDS in a concentration of 0.25%. Characterization techniques indicated a change from the crystalline form to an amorphous form that was molecularly dispersed into the polymer. Flow properties of these microparticles were improved as compared to unprocessed drug. Drug release was enhanced 4-to 5-folds probably due to precipitation of the drug in an amorphous form; wetting enhancement; size reduction and stabilization by polymers and surfactants. In conclusion the selection of proper process parameters enhanced drug release 5 folds. The use of DMSO as a solvent and the preparation of physical mixtures in this research provided a means for controlled or prolonged release.

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Enhancement of Drug Solubility in Supramolecular and Colloidal Systems

Cited by 18 publications

References 26 publications

Poloxamine–Cyclodextrin–Simvastatin Supramolecular Systems Promote Osteoblast Differentiation of Mesenchymal Stem Cells

Poloxamine–Cyclodextrin–Simvastatin Supramolecular Systems Promote Osteoblast Differentiation of Mesenchymal Stem Cells

Preparation and characterization of simvastatin/DMβCD complex and its pharmacokinetics in rats

Preparation and characterization of lovastatin polymeric microparticles by coacervation‐phase separation method for dissolution enhancement

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