Solid dispersions

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Thermal Analysis Study of Flavonoid Solid Dispersions Having Enhanced Solubility

Journal Title, Volume, Page: 
Journal of Thermal Analysis and Calorimetry, Volume 83, Issue 2, pp 283-290
Year of Publication: 
2006
Authors: 
F I Kanaze
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, 54124
Current Affiliation: 
Department of Pharmacy,Faculty of Medicine & Health Sciences, An-Najah National University, Nablus, Palestine
E Kokkalou
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, 54124
I Niopas
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, 54124
M Georgarakis
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece, 54124
A Stergiou
Applied Physics Laboratory, Department of Physics, Aristotle University of
D Bikiaris
Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki, Greece, 54124
Preferred Abstract (Original): 

Purposes of this paper were to prepare and study new drug delivery systems for both flavanone glycosides and their aglycones based on solid-dispersion systems. These compounds are poor water soluble drugs, so an enhancement of their dissolution is a high priority. Solid-dispersion systems were prepared using PVP, PEG and mannitol as drug carrier matrices. Characterizations of these dispersions were done by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). The glass transition (T g) temperature of PVP was only recorded in the DSC thermograms of PVP solid-dispersions of both flavanone glycosides and their aglycones, while in case of PEG and mannitol solid-dispersions endotherms of both glycosides and aglycones were noticed with low peak intensity, indicating that high percent of drug is in amorphous state. The XRD patterns of all PVP solid-dispersions of aglycones show typical amorphous materials, but XRD patterns of their glycosides reveal the presence of crystalline material. However, in all solid dispersions shifts in T gof PVP as well as T m of PEG were observed, indicating the existence of some interactions between drugs and matrices. SEM and TEM microscopy revealed that PVP/aglycone flavanone compounds are nanodispersed systems while all the other solid dispersions are microcrystalline dispersions. The solubility of both flavanone glycosides and their aglycones was directly affected by the new physical state of solid dispersions. Due to the amorphous drug state or nano-dispersions in PVP matrices, the solubility was enhanced and found to be 100% at pH 6.8 in the nano-dispersion containing 20 mass% of aglycones. Also solubility enhancement was occurred in solid dispersions of PEG and mannitol, but it was lower than that of PVP nano-dispersions due to the presence of the drug compounds in crystalline state in both matrices.

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Dissolution Enhancement of Flavonoids by Solid Dispersion in PVP and PEG Matrixes: A Comparative Study

Journal Title, Volume, Page: 
Journal of Applied Polymer Science, Vol. 102, 460 – 471
Year of Publication: 
2006
Authors: 
F. I. Kanaze
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Current Affiliation: 
Department of Pharmacy,Faculty of Medicine & Health Sciences, An-Najah National University, Nablus, Palestine
E. Kokkalou
I. Niopas
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
M. Georgarakis
Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
A. Stergiou
Applied Physics Laboratory, Department of Physics, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece
D. Bikiaris
Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece
Preferred Abstract (Original): 

Polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG) solid dispersion systems with flavanone glycosides, naringin and hesperidin, and their aglycones, naringenin and hesperetin, were prepared, using solvent evaporation method, to enhance their dissolution rates that may affect their bioavailability. Drug release of both flavanone glycosides and their aglycones was directly affected by the physical state of solid dispersions. Powder-XRD technique in combination with scanning and transmission electron microscopy revealed that PVP polymer formed amorphous nanodispersion systems with flavanone aglycones, while such systems could not be formed with their glycosides, which are bulkier molecules. Fourier transform infrared spectra suggest the presence of hydrogen bonds between PVP carbonyl groups and hydroxyl groups of both flavanone aglycones. These interactions prevent the crystallization of naringenin and hesperetin aglycones in PVP matrix. On the other hand, the ability of PEG carrier to form hydrogen bonds with flavanone glycosides or aglycones was limited, and as a result both flavanone glycosides and their aglycones remain in the crystalline form. For this reason, the solubility enhancement of PEG solid dispersions was lower than when PVP was used as drug carrier. At pH 6.8, the % release of naringenin and hesperetin from PVP/naringenin–hesperetin (80/20 w/w) solid dispersion was 100% while in PEG solid dispersions, it was not higher than 60–70%. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 460–471, 2006

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Physicochemical Studies on Solid Dispersions of ‎Poorly Water-Soluble Drugs: Evaluation of ‎Capabilities and Limitations of Thermal ‎Analysis Techniques

Journal Title, Volume, Page: 
Thermochimica Acta Volume 439, Issues 1–2,Pages 58–67
Year of Publication: 
2005
Authors: 
Ferras Kanaze
Section of Pharmaceutics and Drug Control, Department of Pharmacy, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Macedonia, Greece
Current Affiliation: 
Department of Pharmacy,Faculty of Medicine & Health Sciences, An-Najah National University, Nablus, Palestine
Dimitrios Bikiaris
Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece
Anagnostis Stergiou
Department of Physics, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Eleni Pavlidou
Department of Physics, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece
Evangelos Karavas
Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str. 6, Pallini Attikis, 153 51 Attiki, Greece
Manolis Georgarakis
Section of Pharmaceutics and Drug Control, Department of Pharmacy, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Macedonia, Greece
Preferred Abstract (Original): 

Polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG) solid dispersions with Felodipine or Hesperetin having up to 20 wt% drug were prepared using solvent evaporation method. Solid dispersions in comparison with their physical mixtures were studied using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), scanning electron microscopy (SEM) and hot stage polarizing light microscopy (HSM). PVP formulations with low drug load proved to be amorphous, since no crystalline Felodipine or Hesperetin drugs were detected using DSC and WAXD. Low and fast heating rates were applied for DSC study, to prevent changes in the samples caused during heating. Similarity between results of WAXD and DSC was also found in the case of physical mixtures, where the drug was in the crystalline state. However, though specific tests showed the high sensitivity of the DSC technique, it was difficult to arrive to reliable results for PEG solid dispersions or physical mixtures with low drug content by DSC, even by high heating rates. Crystalline drug could not be detected by DSC, leading to erroneous conclusions about the physical state of the drug, in contrast to WAXD. On the other hand, HSM proved the presence of small drug particles in the solid dispersions with PEG and the dissolution of the drug in the melt of PEG on heating. In such systems, in which a polymer with low melting point is used as drug carrier, DSC is inappropriate technique and must be used always in combination with HSM. The coupling of WAXD with thermal analysis, allowed complete physicochemical characterization and better understanding which is essential for a first prediction of dissolution characteristics of such formulations.

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