TY - JOUR
T1 - Effect of the preparation method on crystallinity, particle size, aqueous solubility and dissolution of different samples of the poorly water-soluble fenofibrate with HP-β-CD
AU - Yousaf, Abid Mehmood
AU - Kim, Dong Wuk
AU - Cho, Kwan Hyung
AU - Kim, Jong Oh
AU - Yong, Chul Soon
AU - Choi, Han Gon
N1 - Publisher Copyright:
© 2014 Springer Science+Business Media Dordrecht.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - To determine the effect of the preparation method on the physicochemical properties, such as crystallinity, particle size, solubility and dissolution, of the poorly water-soluble fenofibrate, different samples were prepared from fenofibrate and hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 1:1 molar ratio, by physical mixing, trituration, kneading, solvent-evaporation and spray-drying techniques. The corresponding aqueous solubilities and dissolutions were studied in comparison with that of the drug powder. Characterization of these samples was accomplished using particle size determination, powder x-ray diffraction, differential scanning calorimetry, thermogravimetry, scanning electron microscopy and Fourier transform infrared spectroscopy. All preparations improved the solubility and dissolution of the drug, as compared with that of the drug powder (P<0.05), in the following descending order of techniques utilized: spray-drying > solvent-evaporation > kneading > trituration > physical mixing. In particular, the aqueous solubility of fenofibrate from the spray-dried preparation was 85.93 ± 6.82 μg/ml, and the dissolution was about 90 % within 20 min. The drug was present in the crystalline state in the physically mixed, triturated and kneaded preparations. However, it was converted into the amorphous state in the solvent-evaporated and spray-dried preparations. The spray-dried preparation having the smallest particle size of 2.44 ± 0.03 lm gave discrete particles. Thus, in the development of a preparation of the poorly water-soluble fenofibrate with HP-β-CD, the preparation method exhibits a significant effect on the physicochemical properties of the drug. Among the various preparations tested in this study, the spray-dried sample, which provided the highest solubility and dissolution of fenofibrate, is strongly recommended for possible administration via the oral route.
AB - To determine the effect of the preparation method on the physicochemical properties, such as crystallinity, particle size, solubility and dissolution, of the poorly water-soluble fenofibrate, different samples were prepared from fenofibrate and hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 1:1 molar ratio, by physical mixing, trituration, kneading, solvent-evaporation and spray-drying techniques. The corresponding aqueous solubilities and dissolutions were studied in comparison with that of the drug powder. Characterization of these samples was accomplished using particle size determination, powder x-ray diffraction, differential scanning calorimetry, thermogravimetry, scanning electron microscopy and Fourier transform infrared spectroscopy. All preparations improved the solubility and dissolution of the drug, as compared with that of the drug powder (P<0.05), in the following descending order of techniques utilized: spray-drying > solvent-evaporation > kneading > trituration > physical mixing. In particular, the aqueous solubility of fenofibrate from the spray-dried preparation was 85.93 ± 6.82 μg/ml, and the dissolution was about 90 % within 20 min. The drug was present in the crystalline state in the physically mixed, triturated and kneaded preparations. However, it was converted into the amorphous state in the solvent-evaporated and spray-dried preparations. The spray-dried preparation having the smallest particle size of 2.44 ± 0.03 lm gave discrete particles. Thus, in the development of a preparation of the poorly water-soluble fenofibrate with HP-β-CD, the preparation method exhibits a significant effect on the physicochemical properties of the drug. Among the various preparations tested in this study, the spray-dried sample, which provided the highest solubility and dissolution of fenofibrate, is strongly recommended for possible administration via the oral route.
KW - Crystallinity
KW - Dissolution
KW - Fenofibrate
KW - Inclusion
KW - Particle size
KW - Preparation method
KW - Solubility
UR - http://www.scopus.com/inward/record.url?scp=84957092550&partnerID=8YFLogxK
U2 - 10.1007/s10847-014-0461-z
DO - 10.1007/s10847-014-0461-z
M3 - Article
AN - SCOPUS:84957092550
SN - 0923-0750
VL - 81
SP - 347
EP - 356
JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry
JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry
IS - 3-4
ER -