Efficient Enhancement in Itraconazole Solubility through its Cyclodextrin-Water Soluble Polymer Ternary Inclusion Complexes (original) (raw)
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Comparative study of itraconazole-cyclodextrin inclusion complex and its commercial product
Archives of Pharmacal Research, 2010
Itraconazole (ITZ) solid complex using hydroxypropyl-β-cyclodextrin (ITZ-HP-β-CD) with 20% polyvinylpyrrolidone was prepared by a co-evaporation method. The complex improved antifungal activity against C. parapasilosis and C. albicans. The complex demonstrated good flow and compressibility characteristics. The complex was formulated as a capsule dosage form and drug release was evaluated. Capsules containing ITZ-HP-β-CD at a molar ratio of 1:3 with 20% polyvinylpyrrolidone have a faster dissolution rate than commercial capsules (Sporanox ® ). About 88% of ITZ was released in less than 30 min and the initial dissolution rate exhibited a 3.5-fold increase compared to the commercial product. UV spectrophotometeric, HPLC, and antimicrobial methods were used to determine ITZ concentration in the release medium and the results obtained by these methods are reported. It was found that HPLC analysis is a suitable and reliable method for determination of the drug concentration with a coefficient of variation less than 10%. The intraday precision showed a coefficient of variation less than 3.96%, and that for interday was less than 4.99%. The HPLC method was more accurate and precise than the antimicrobial and UV-spectrophotometric methods for determination of ITZ concentration present in the release medium.
2010
The rationale of this study was to enhance solubility and dissolution rate of Gliclazide(GLD) by complexation with I²-cyclodextrin (I²-CD) and subsequent disperson with water-soluble polymers. The water-soluble polymers used were Hydroxypropyl methylcellulose 5cps, Polyvinylpyrrolidone K30, Avicel pH101, Polyethylene glycol 4000 and Croscarmellose sodium. The GLD-I²-CD complex was prepared at the concentration of 1:1.5 molar ratios by coprecipitation method and the polymers were added at the concentration of 5%w/w to the complex by kneading. The binary system was characterized by differential scanning calorimetry, IR spectroscopy and X-ray diffractometry. Phase solubility studies revealed that the complexation with I²-CD increases the solubility of drug. All the ternary systems showed higher dissolution efficiency compared to the binary system. The Gibbs free energy change (IÂÂÂÂÂGtrÂo) values are negative for all the binary and ternary systems, indicating the spontaneous nature of...
Studies on the Effect of Water-Soluble Polymers on Drug–Cyclodextrin Complex Solubility
AAPS PharmSciTech, 2009
The effect of complexation of irbesartan (IRB), a practically water-insoluble drug, with cyclodextrins in presence of different concentrations of water-soluble polymers (PEG 4000 and PVP K-90) on the dissolution rate of the drug has been investigated. Phase solubility studies were carried out to evaluate the solubilizing power of βCD in association with water-soluble polymers towards IRB and to determine the apparent stability constant (K S) of the complexes. Improvement in K S value for ternary complexes (IRB-βCD-polymers) clearly proved the benefit on the addition of water-soluble polymer to increase complexation efficiency. The dissolution rate of the drug from ternary systems containing PEG 4000 and PVP K-90 was higher as compared to the binary system. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% w/w for PVP K-90 and 10% w/w for PEG 4000. DSC, FTIR, SEM, and XRD studies were carried out to characterize the complexes.
Journal of Pharmaceutical Sciences, 2006
Phase-solubility techniques were used to assess the formation of inclusion complex between itraconazole and b-cyclodextrin. The stability constant and free energies of transfer of itraconazole from aqueous solution to the cavity of b-cyclodextrin were calculated. Itraconazole solubility in supercritical carbon dioxide (SC CO 2) was measured at different temperatures and pressures. Drug formulations of itraconazole were prepared by complexation of the drug into b-cyclodextrin using SC CO 2. Effects of temperature and pressure on inclusion yield of the prepared complexes were studied. The solvent-free inclusion complexes obtained from this method were characterized by UV spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and compared to those obtained from physical mixing and coprecipitation methods. Results showed that b-cyclodextrin significantly improved solubility of itraconazole in aqueous solutions. The free energies of transfer of itraconazole from aqueous solution to the cavity of b-cyclodextrin increased negatively with increasing b-cyclodextrin concentration. Higher inclusion yields were obtained in the SC CO 2 method compared to physical mixing and coprecipitation methods. Both temperature and pressure had significant effects on itraconazole solubility in SC CO 2 and the inclusion yield of the complex prepared by SC CO 2 method.
International Journal of Applied Pharmaceutics
Objective: The purpose of the present study was to enhance solubility and dissolution characteristics of indomethacin by preparing inclusion complexes with hydroxypropyl β-cyclodextrin (HP β-CD) and solid dispersions with PEG 6000 to enhance its in vitro drug release and to further formulate it as a tabletMethods: Solid dispersions (SDs) and inclusion complexes (ICs) of Indomethacin with PEG 6000 and HP β-CD respectively were prepared to enhance the dissolution rate of this poorly water-soluble drug belonging to BCS class II. A comparison was made between two systems: solid dispersions with PEG 6000 obtained using melting and solvent evaporation technique, inclusion complexes with HP β-CD prepared by kneading technique. SDs were prepared in 1:1, 1:2, 1:3 and ICs in 1:0.25, 1:0.5, 1:1 w/w ratios of drug: polymer. Both the systems were characterized by FTIR, SEM, DSC, X-RD.Results: The dissolution of indomethacin increased with the increase in the concentration of the polymers. F4 and...
Ditosylate Salt of Itraconazole and Dissolution Enhancement Using Cyclodextrins
AAPS PharmSciTech, 2012
Salt formation has been a promising approach for improving the solubility of poorly soluble acidic and basic drugs. The aim of the present study was to prepare the salt form of itraconazole (ITZ), a hydrophobic drug to improve the solubility and hence dissolution performance. Itraconazolium ditolenesulfonate salt (ITZDITOS) was synthesized from ITZ using acid addition reaction with p-toluenesulfonic acid. Salt characterization was performed using 1 H NMR, mass spectrometry, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The particle size and morphology was studied using dynamic light scattering technique and scanning electron microscopy, respectively. The solubility of the salt in water and various pharmaceutical solvents was found multifold than ITZ. The dissolution study exhibited 5.5-fold greater percentage release value in 3 h of ITZDITOS (44.53%) as compared with ITZ (8.54%). Results of in vitro antifungal studies using broth microdilution technique indicate that ITZDITOS possessed similar antifungal profile as that of ITZ when tested against four fungal pathogens. Furthermore, the physical mixtures of ITZDITOS with two cyclodextrins, βcyclodextrin (β-CD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared in different molar ratios and were evaluated for in vitro release. It was observed that in only 30 min of dissolution study, about 74 and 81% of drug was released from 1:3 molar ratios of ITZDITOS with β-CD and ITZDITOS with HP-β-CD, respectively, which was distinctly higher than the drug released from ITZ commercial capsules (70%). The findings warrant further preclinical and clinical studies on ITZDITOS so that it can be established as an alternative to ITZ for developing oral formulations.
International Journal of Applied Pharmaceutics, 2018
Objective: The purpose of the present study was to enhance solubility and dissolution characteristics of indomethacin by preparing inclusion complexes with hydroxypropyl β-cyclodextrin (HP β-CD) and solid dispersions with PEG 6000 to enhance its in vitro drug release and to further formulate it as a tablet Methods: Solid dispersions (SDs) and inclusion complexes (ICs) of Indomethacin with PEG 6000 and HP β-CD respectively were prepared to enhance the dissolution rate of this poorly water-soluble drug belonging to BCS class II. A comparison was made between two systems: solid dispersions with PEG 6000 obtained using melting and solvent evaporation technique, inclusion complexes with HP β-CD prepared by kneading technique.
2015
The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between different drugs and cyclodextrins (econazole and α-cyclodextrin; indomethacin and methyl-β-cyclodextrin; olanzapine and methyl-β-cyclodextrin; flurbiprofen and methyl-β-cyclodextrin) in order to enhance the apparent solubility and dissolution properties of drugs. Specifically, the effectiveness of supercritical carbon dioxide processing for the preparation of solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. Nitrate, besylate, sulfosalicylate dihydrate and maleate salts of econazole were synthesised. The solid drug-cyclodextrin inclusion complexes were prepared by physical mixing, freeze drying from aqueous solution and processing with supercritical carbon dioxide. The complexes were evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, 1H-nuclear...
Journal of Inclusion Phenomena and …
Fluconazole (FZ) is a triazole antifungal drug administered orally or intravenously. It is employed for the treatment of mycotic infections. However, the efficacy of FZ is limited with its poor aqueous solubility and low dissolution rate. One of the important pharmaceutical advantages of cyclodextrins is to improve pharmacological efficacy of drugs due to increasing their aqueous solubility. The aim of present study was to prepare an inclusion complex of FZ and b-cyclodextrin (b-CD) to improve the physicochemical and biopharmaceutical properties of FZ. The effects of b-CD on the solubility of FZ were investigated according to the phase solubility technique. Complexes were prepared with 1:1 M ratio by different methods namely, freeze-drying, spray-drying, co-evaporation and kneading. For the characterization of FZ/b-CD complex, FZ amount, practical yield %, thermal, aqueous solubility, XRD, FT-IR and NMR (1 H and 13 C) analysis were performed. In vitro dissolution from hard cellulose capsules containing FZ/b-CD complexes was compared to pure FZ and its commercial capsules and evaluated by f 1 (difference) and f 2 (similarity) factors. Paddle method defined in USP 31 together with high pressure liquid chromatographic method were used in in vitro dissolution experiments. It was found that solubility enhancement by FZ/b-CD complexes depends on the type of the preparation method. High release of active agent from hard cellulose capsules prepared with b-CD complexes compared to commercial capsules was attributed to the interactions between b-CD and active agent, high energetic amorphous state and inclusion complex formation.
Formulation of betacyclodextrin based nanosponges of itraconazole
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2007
Nanosponges are betacyclodextrins crosslinked with carbonate bonds. The polymer formed is nanoparticulate in nature. Itraconazole is a BCS Class II drug that has a dissolution rate limited poor bioavailability. Rationale of the work was to enhance the solubility of Itraconazole so that the bioavailability problems are solved. Solid dispersion technique has been used for drug incorporation. The effect of a ternary component copolyvidonum on solubility of itraconazole has been studied. Phase solubility studies has been carried out with a rationale of comparing the solubilization efficiency of nanosponges, copolyvidonum and combination. The dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and photon correlation spectroscopy (PCS). It was found that the solubility of itraconazole was enhanced more than 50-folds with a ternary solid dispersion system. Using copolyvidonum in conjunction with nanosponges helps to increase the solubilization efficiency of nanosponges as evident from the phase solubility studies.