ABSTRACT
The aim of the present study is to improve the solubility and antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin by formulating its inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin in solution and in solid state. The phase solubility study was used to investigate the interactions between 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and 2-hydroxypropyl-ß-cyclodextrin and to estimate the molar ratio between them. The structural characterization of binary systems (prepared by physical mixing, kneading and solvent evaporation methods) was analysed using the FTIR-ATM spectroscopy. The antimicrobial activity of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin and inclusion complexes prepared by solvent evaporation method was tested by the diffusion and dilution methods on various strains of microorganisms. The results of phase solubility studies showed that 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin formed the inclusion complexes with 2-hydroxypropyl-ß-cyclodextrin of AP type. The solubility of 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin was increased 64.05-fold with 50% w/w of 2-hydroxypropyl-ß-cyclodextrin at 37 oC. The inclusion complexes in solid state, prepared by the solvent evaporation method, showed higher solubility in purified water and in phosphate buffer solutions in comparison with 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin alone. The inclusion complexes prepared by solvent evaporation method showed higher activity on Bacillus subtilis and Staphylococcus aureus compared to uncomplexed 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin due to improved aqueous solubility, thus increasing the amount of available 3-(3-(2-chlorophenyl)prop-2-enoyl)-4-hydroxycoumarin that crosses the bacterial membrane.
Subject(s)
Solubility , Cyclodextrins/agonists , Anti-Infective Agents , Spectrum Analysis/instrumentation , Staphylococcus aureus/classification , Bacillus subtilis/classification , Spectroscopy, Fourier Transform Infrared , DilutionABSTRACT
Objective: The inclusion compound of silymarin-SBE-β-CD was prepared. Methods: Phase solubility method was used to screen the inclusion materials of cyclodextrin and determine the type of inclusion. The technological conditions of silymarin inclusion complex were optimized by orthogonal design. The solubility of inclusion was determined and its structure was characterized by means of microscope, infrared spectrum analysis and X-ray diffraction analysis. Results: Due to its higher solubilization effect on silymarin, SBE-β-CD was determined as inclusion material. The ratio of drug to cyclodextrin was coated in the mode of 1:n. The process optimized by orthogonal design was as follow: molar ratio of silymarin to SBE-β-CD of 1:8, inclusion temperature of 60 ℃, and inclusion time of 3 h. Microscope, infrared spectrum analysis and X-ray diffraction analysis showed that the inclusion compound was formed and the drug existed in the inclusion compound as amorphous. Conclusion: The inclusion compound of silymarin-SBE-β-CD has been successfully prepared, which can significantly improve the solubility of the drug, and provide experimental basis for its clinical application.
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Objective: To study the solubilization of sulfonated butyl ether-β-cyclodextrin (SBE-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) for voriconazole (VCZ) to lay basis for the preparation of inclusion compounds of VCZ.Methods: The phase-solubility method was used, and the solubilization of SBE-β-CD and HP-β-CD at different concentrations for VCZ was studied at various temperatures and the inclusion constant (K) and such inclusion parameters as ΔG, ΔH and ΔS were calculated.Results: Both SBE-β-CD and HP-β-CD could improve the solubility of VCZ in water, while the solubilization of SBE-β-CD was more significant than that of HP-β-CD at the same concentration under the same temperature.The equilibrium phase-solubility diagram of SBE-β-CD vs VCZ was AN type, and that of HP-β-CD vs VCZ was AL type.With the increase of temperature, K of both β-CD decreased.ΔG, ΔH and ΔS were all negative for the inclusion process.Conclusion: Compared with that of HP-β-CD, the solubilization of SBE-β-CD for VCZ is better.The inclusion is spontaneously formed with exothermic process, and the main acting force is Van der Waals'' force.
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OBJECTIVE: To improve the solubility of prasugrel in aqueous solution, the solubilization effect of SBE-β-CD and HP-β-CD research on prasugrel.
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The drug 5 fluorouracil is sparingly soluble in water. The aqueous solubility and dissolution rate of 5-fluorouracil can be increased by inclusion complexation with β-cyclodextrin. Molecular-modeling studies support the formation of stable molecular inclusion complexation of 5-fluorouracil with β-cyclodextrin monomer (1:1). Complexes were prepared by physical mixture, kneading, co evaporation and freeze drying methods. Two ratios 1:1 and 1:2 were formulated. These eight complexes were subjected to Phase-solubility study, molecular modeling and dissolution study. The complexes formed were confirmed by DSC studies. Phase solubility profile indicated that the solubility of 5-fluorouracil increased in the presence of β-cyclodextrin monomer. Results obtained by different characterization techniques clearly indicate that the freeze-drying method leads to formation of solid state complexes between 5-fluorouracil and β-cyclodextrin. The complexation of 5-fluorouracil with β- cyclodextrin lends an ample credence for better therapeutic efficacy.
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Solid dispersions of ibuprofen (IBU) were prepared by solvent evaporation method using polyvinyl pyrrolidone (PVP) and/or sodium lauryl sulphate (SLS). Physicochemical properties of the various solid dispersion systems were determined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The results from dissolution studies indicated that ternary solid dispersion systems were more efficacious than the corresponding binary ones. The increase in the dissolution rate of ibuprofen from its solid dispersions with the PVP and/or SLS used in this study could be attributed to several factors such as improved wettability, local solubilisation, and drug particle size reduction. The most effective solid dispersion was the 20:180:10 w/w IBUPVP- SLS ternary system, which allowed dissolution of 85 % drug after only 9.15 minutes (in comparison with 94.61 minutes for drug alone and 17.92 minutes for the binary system).
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Objective To prepare and identify the andrographolide-hydroxypropyl-?-cyclodextrin(an- drographolide-HP-?-CD)inclusion compound.The tool ratio between andrographolide and HP-?-CD and the thermodynamic constants in inclusion were studied simultaneously.Methods The andrographolide- HP-?-CD inclusion compound was prepared with lyophilization technique.Meanwhile,the inclusion com- pound was identified by differential scanning calorimetry(DSC)methods,infrared spectrometry(IR),and X-ray diffraction(XRD),respectively.The tool ratio between host and guest moleculars and the thermo- dynamic constants during the inclusion process were also researched by phase solubility method.Results An 1:1 molar ratio inclusion complex of andrographolide with HP-?-CD could be formed at 25,35,and 45 C.The phase diagram was A_L type and the procedure of inclusion was a heat release process.Conclusion The solubility of andrographolide-HP-?-CD inclusion compound can be increased obviously by the above- mentioned preparing techniques.
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AIM: To optimize the preparation of cholic acid-hydroxypropy-?-cyclodextrin inclusion complex,and its phase solubility analysis. METHODS: Orthogonal test,including molar ratio,inclusion temperature,mixing time and liquid dropping rate of cholic acid-HP-?-CD,was adopted to screen the optimal preparation,based on the inclusion efficiency by HPLC method.The solubilization effect was evaluated by using phase solubility.(RESULTS): The optimal preparation consisted of the molar ratio of cholic acid-HP-?-CD was 1∶3,60 ℃ inclusion temperature,60 min mixing time,1.6 mL/min liquid dropping rate;A_L type of phase solubility curve,K=564.30 L/mol,and 11.81 times solubilization. CONCLUSION: The optimal preparation is stable,reasonable and practicable with the encapsulation efficiency of 97.1%.Inclusing cholic acid with HP-?-CD is feasible,and the solubilization effect is significant.