The interaction between FSM-16 and flurbiprofen (FBP) in the mesopores of FSM-16 was investigated by using three types of FSM-16 with different pore diameters, i.e., FSM-16(Oc), FSM-16(Do) and FSM-16(Doc) (pore diameters 16.0, 21.6, 45.0 Å, respectively). Solid dispersions of 30% FBP–70% FSM-16 were prepared by solvent evaporation and sealed-heating of the physical mixture at 100 °C for 6 h. Changes in the molecular state of FBP were investigated using powder X-ray diffractometry, thermal analysis and FT-IR spectroscopy. The changes in pore diameter and specific surface area of FSM-16 systems were investigated by small angle X-ray scattering and nitrogen gas adsorption. Powder X-ray diffractometry and thermal analysis revealed that FBP was adsorbed onto the mesopores of FSM-16(Do) and FSM-16(Doc), leading to an amorphous state, while no change was observed for FSM-16(Oc). Fourier-transformed IR spectroscopy showed a hydrogen bond interaction between the carbonyl groups of FBP and the silanol groups of FSM-16. The pore diameter and specific surface area of FSM-16 in solid dispersions decreased due to the adsorption of FBP. Improved dissolution of FBP from solid dispersions prepared by the evaporation and the sealed-heating methods was observed in comparison with FBP crystals.
The inclusion compound formation between linear amylose of molecular weight 102500 (AS100) and p-aminobenzoic acid (PA) during the sealed-heating process was investigated by powder X-ray diffractometry, infrared spectroscopy and solid state NMR spectroscopy. Sealed-heating of AS100 and PA at 100 °C for 6 h provided an inclusion compound with 61-helix structure, while a 71-helix structure was found when sealed-heating was carried out at 150 °C for 1 h. The formation of an inclusion compound was not observed when sealed-heating was performed at 50 °C for 6 h. The 71-helix inclusion compound maintained its structure even during storage at high temperature while the 61-helix inclusion compound decomposed and returned to the original Va-amylose upon heating to 180 °C. Quantitative determination revealed that one PA molecule could be included per one helical turn of AS100 for both 61-helix and 71-helix inclusion compounds. Solid state NMR spectroscopy suggested that PA molecules were included in the amylose helix core in the 71-helix inclusion compound, while in the case of 61-helix inclusion compound, PA molecules were accommodated in the interstices between amylose helices. Moreover, the inclusion compound formation by sealed-heating of AS100 was also observed when using PA analogues as guest compounds. The binding ratio of AS100 and PA analogues varied depending on the size of guest molecules.
The aim of this study was to investigate the factors affecting the formation of pranlukast nanoparticle prepared by co-grinding with β-cyclodextrin (β-CD) and to elucidate the mechanism of nanoparticle formation. The effects of grinding time, moisture content and CD content on the nanoparticle formation were evaluated by means of UV quantitative determination and particle size analysis. High-resolution scanning electron microscopy (HRSEM) was employed to observe drug nanoparticles in the ground mixture. Nanoparticle recovery was higher than 95% for 2 : 1 molecular mixtures of β-CD : pranlukast which had been ground for 10 min with moisture levels between 10 and 15%. While that of the 1 : 2 ground mixture prepared at 8% moisture level was only 57%. Nanoparticle recovery from β-CD : pranlukast 2 : 1 mixture ground for 1 min was 2.5%, while that of the 10 min ground mixture was as high as 95%. HRSEM demonstrated that primary drug nanoparticles having a particle size around 50 nm were observed in the ground mixture. The grinding time, the moisture content, and the CD content had significant influences on the formation of drug nanoparticles. The CD matrix may form and stabilize primary particles by its interaction with the particle surface through water molecules. Primary nanoparticles existed in the ground mixture as 50 nm drug nanocrystallites.
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