Biomedical subjects

Yuichi Tozuka

Publications and source records attributed to Yuichi Tozuka.

At least 19 recordsLinked to original sources

PubMed2006

Application of ascorbic acid 2-glucoside as a solubilizing agent for clarithromycin: solubilization and nanoparticle formation.

Clarithromycin (CAM) was co-ground with l-ascorbic acid 2-glucoside (AA-2G), a newly developed food additive, to improve the solubility characteristics. The complete solubilizing effect of AA-2G was observed for the ground mixture with 1:1 molar ratio. When ground mixtures of CAM and AA-2G (2:1) were dispersed into water, not only the solubilization of CAM was observed but also nanoparticle formation with a mean particle diameter of 280 nm. The CAM particles obtained in this manner were stable in suspension for at least 7 days. Zeta potential analysis showed that positive charges on the particle surface may be contributing to the stability of the suspension. 1H NMR spectrum of CAM dissolved in a phosphate buffer (pH 5.5) showed a signal derived from the N,N-dimethylamino group at 2.73 ppm, while that of an equimolar ground mixture of CAM with AA-2G in D2O (pH 5.5) showed clearly two signals at 2.65 and 2.77 ppm derived from the splitting of the two methyl groups. The 13C NMR spectrum of the equimolar ground mixture dissolved in D2O exhibited two signals derived from N,N-dimethyl carbons of desosamine group at 37.2 and 42.3 ppm, whereas unprocessed CAM showed no resonance signal arising from those carbons. Moreover, the carbon resonance at 163 and 173 ppm arising from the ketone group in the CAM lactone ring shifted downfield to 177 and 180 ppm after the co-grinding with AA-2G. The formation of nanoparticles was only observed when CAM was co-ground with AA-2G in the molar ratio of 2:1, which might be attributable to a grinding-induced interaction in the solid-state via the ketone group in lactone ring of CAM.

Anti-Bacterial Agents↗

PubMed2006

Molecular interaction among probucol/PVP/SDS multicomponent system investigated by solid-state NMR.

PURPOSE: Effects of polyvinylpyrrolidone (PVP) molecular weight on the solid-state intermolecular interactions among probucol/PVP/sodium dodecyl sulfate (SDS) ternary ground mixtures (GM) and the formation of nanoparticles were investigated by solid-state NMR spectroscopy. MATERIALS AND METHODS: Ternary GMs of probucol were prepared with PVP (K12, K17, K30 or K90) and SDS at a weight ratio of 1:3:1 and were ground for 15, 30 and 60 min. Solid-state interactions were evaluated using powder X-ray diffraction (PXRD) and solid-state cross polarization/magic angle spinning (CP/MAS) (13)C NMR spectroscopy. A high resolution scanning electron microscopy (SEM) was employed to observe nanoparticles of probucol in the GM. RESULTS: The solid-state (13)C CP/MAS NMR results indicate that the low molecular weight PVP interacts with probucol and SDS more strongly than the high molecular weight PVP in the ternary GM. This finding was consistent with the result that smaller drug nanoparticles were obtained using low molecular weight of PVP. SEM images of probucol/PVP K12/SDS confirmed the presence of nanoparticles (15-25 nm) in the GM. CONCLUSIONS: Grinding-induced solid-state interactions among drug, PVP and SDS could be detected using solid state (13)C NMR. The interactions in both probucol-PVP and PVP-SDS should occur simultaneously to generate nanometer-sized particles of probucol.

Magnetic Resonance Spectroscopy↗

PubMed2006

Specific inclusion mode of guest compounds in the amylose complex analyzed by solid state NMR spectroscopy.

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 degrees C for 6 h provided an inclusion compound with 6(1)-helix structure, while a 7(1)-helix structure was found when sealed-heating was carried out at 150 degrees C for 1 h. The formation of an inclusion compound was not observed when sealed-heating was performed at 50 degrees C for 6 h. The 7(1)-helix inclusion compound maintained its structure even during storage at high temperature while the 6(1)-helix inclusion compound decomposed and returned to the original V(a)-amylose upon heating to 180 degrees C. Quantitative determination revealed that one PA molecule could be included per one helical turn of AS100 for both 6(1)-helix and 7(1)-helix inclusion compounds. Solid state NMR spectroscopy suggested that PA molecules were included in the amylose helix core in the 7(1)-helix inclusion compound, while in the case of 6(1)-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.

4-Aminobenzoic Acid↗

PubMed2005

Rapid adsorption and entrapment of benzoic acid molecules onto mesoporous silica (FSM-16).

Changes in the molecular state of benzoic acid (BA) in the presence of folded sheet mesoporous material (FSM-16), which has uniformly sized cylindrical mesopores and a large surface area, were assessed with several analyses. When BA was blended with FSM-16 for 5 min (BA content=30%), the X-ray diffraction peaks of BA crystals disappeared, suggesting an amorphous state. Fluorescence analysis of the mixture showed a new fluorescence emission peak for BA at 386 nm after mixing with FSM-16. Fluorescence lifetime analysis of the BA component in the mixture at 386 nm showed a longer lifetime in comparison with that of BA crystals. The solid-state (13)C CP/MAS and PST/MAS NMR spectra of the mixture with FSM-16 showed a significantly different spectral pattern from the mixture with nonporous glass, whose NMR spectra were identical to those of BA crystals. These results indicate that BA molecules disperse quickly into the hexagonal channels of FSM-16 by a simple blending procedure and adsorbed BA molecules had clearly different physicochemical properties to BA crystals.

Adsorption↗

PubMed2005

Micronization of phenylbutazone by rapid expansion of supercritical CO2 solution.

Rapid expansion of supercritical solutions (RESS) technique was applied for the preparation of phenylbutazone fine particles. The operating temperature and pressure affected the yield of the drug fine particles, which was evaluated by dissolving the sprayed product of drug into ethanol. Effect of pre- and post-expansion conditions on the particle size distribution of phenylbutazone was investigated and the smallest sample (mean particle size: 1.59 microm) was obtained when the RESS method was operated at a pressure of 26 MPa combined with a temperature of 32 degrees C. Physicochemical properties of the fine particles were investigated by powder X-ray diffraction and differential scanning calorimetry. It was found that the phenylbutazone fine particles obtained were meta-stable beta form under the experimental conditions tested, suggesting polymorphic transformation during the RESS process.

Calorimetry, Differential Scanning↗

PubMed2005

Water vapor adsorption behavior of sodium deoxycholate anhydrous forms.

Pseudopolymorphism of sodium deoxycholate (NaDC) was investigated. Intact NaDC (dihydrate) was dried at 60 degrees C under reduced pressure resulting an anhydrous amorphous phase. On the other hand, intact NaDC was altered to an anhydrous crystalline form by heating at 200 degrees C. The water vapor adsorption and desorption isotherms of dehydrated NaDCs were determined using an automatic gravimetric water vapor adsorption analyzer. In the case of NaDC dehydrated at 60 degrees C, the weight was increased in rising relative humidity and it was transformed into the NaDC tetrahydrate above 60% RH, which was identified by TG/DTA and powder X-ray diffraction. During the water vapor adsorption process of the sample dehydrated at 200 degrees C, the NaDC dihydrate was obtained in the range of 50 to 70% RH and then transformed into the NaDC octahydrate above 85% RH. The NaDC octahydrate was characterized by TG/DTA and powder X-ray diffraction for the first time. During the desorption process, the octahydrate was changed to the tetrahydrate between 80 and 40% RH.

Adsorption↗

PubMed2005

Effect of pore size of FSM-16 on the entrapment of flurbiprofen in mesoporous structures.

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 A, respectively). Solid dispersions of 30% FBP-70% FSM-16 were prepared by solvent evaporation and sealed-heating of the physical mixture at 100 degrees 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.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Influence of dehydration temperature on water vapor adsorption, dissolution behavior and surface property of ampicillin.

Several specimens of anhydrous ampicillin were prepared by heating the ampicillin trihydrate at 100, 120, 140 and 160 degrees C. The effects of dehydration temperature on water vapor adsorption, dissolution behavior and surface property were investigated. The water vapor adsorption of anhydrous ampicillin was studied at 89% relative humidity, 40 degrees C and the water vapor adsorption rate was found to decrease with increase of dehydration temperature. Dissolution profiles of the various anhydrous specimens were investigated in 96% ethanol at 35 degrees C by the static disk method. The anhydrous form prepared at higher dehydration temperature exhibited faster dissolution rate. Solid phase transformation from the anhydrous form to the trihydrate form occurred during the dissolution test. The rate of phase transformation during the dissolution test decreased with increasing dehydration temperature. Topographic difference of the anhydrous forms prepared at 100 and 160 degrees C was not observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM); however, difference of the microstructural properties was apparently observed by the AFM phase image. Surface free energy study revealed that when ampicillin was dehydrated at high temperature, the sample surface became more hydrophobic resulting in less interaction force with water and slow water sorption rate. From the results, we concluded that the polarity of sample surface induced by dehydration of ampicillin would affect the phase transformation and dissolution behavior.

Adsorption↗

PubMed2004

Modification of physicochemical and mechanical properties of shellac by partial hydrolysis.

The shellac was modified by partial hydrolysis with 2.0% (w/w) NaOH for different times. The hydrolysed shellac was then evaluated for physicochemical and film properties in comparison with native shellac. The tablets coated with native and hydrolysed shellac were also evaluated. The results demonstrated that acid value (AV) of shellac increased with prolongation of hydrolysis time. The solubility of shellac in buffer solution (pH < or = 7) gradually increased with increasing hydrolysis time. The films prepared from hydrolysed shellac were more flexible and soft than those prepared from native shellac. The increasing of flexibility was correlated with the increasing of soft resin in shellac. The water vapor permeability of hydrolysed shellac film was lower than that of native shellac film. The higher acid permeability of the tablet coated with hydrolysed shellac was observed. In ethanol-based film coating, shellac had lower solubility and thus lower drug dissolution from coated tablets was observed. In ammonia-based film coating, the solubility of shellac was improved higher nearby pH 7.0 by an ammonium neutralisation method because of forming well-soluble salts, thereby higher drug dissolution was obtained. Partial hydrolysis provided modified shellac, which is more effective for ammonium salt formation, thus very higher drug dissolution was achieved in the ammonia-based coated tablets.

Chemical Phenomena↗

PubMed2004

Grinding-induced equimolar complex formation between thiourea and ethenzamide.

We prepared and characterized a grinding-induced equimolar complex of thiourea with ethenzamide. When thiourea and ethenzamide were co-ground at a molar ratio of 3 : 1, new powder X-ray diffraction (PXRD) peaks were observed in addition to PXRD peaks of thiourea crystals. The optimum stoichiometry of the new structure was confirmed as 1 : 1 mol/mol. Effect of grinding time on the thiourea-ethenzamide equimolar complex formation was investigated by using PXRD, differential scanning calorimetry and Fourier transform infrared spectroscopy. The equimolar crystal structure was confirmed by X-ray diffraction measurements of the single crystal which was recrystallized from ethanol. It was found that the intermolecular hydrogen bond formations between thiourea and ethenzamide molecules contributed to the equimolar complex formation. The complex formation was not observed in the cases where benzamide, salicylamide or 3-ethoxybenzamide was co-ground with thiourea. 2-Alcoxyl benzamide structures should be required for the grinding-induced equimolar complex formation with thiourea.

Salicylamides↗

PubMed2003

Formation of fine drug particle by cogrinding with cyclodextrins. Part II. The influence of moisture condition during cogrinding process on fine particle formation.

The purpose of this study was to investigate the effect of moisture condition during cogrinding process on fine drug particle formation. Cogrinding of cyclodextrins (CDs) and pranlukast (PRK) hemihydrate was performed in various moisture conditions at a mixing molar ratio of 2:1 (CDs:PRK) and the formation of PRK submicron particle was investigated. The moisture content in the cogrinding process significantly affected the fine particle formation. More than 90% of pranlukast loaded transformed to submicron particles when coground with alpha-CD, beta-CD or gamma-CD containing the specific amount of water for each CD system. Fine particle formation of PRK was considered as a particular phenomenon to cyclodextrins, since the submicron particles could not be formed when D-mannitol, lactose or microcrystalline cellulose (MCC) was used as a cogrinding additive. Moreover, the appearance and disappearance of fine particle formation was found to be reversible depending on the existence of water during the grinding process.

Chromones↗

PubMed2003

Supercritical carbon dioxide treatment as a method for polymorph preparation of deoxycholic acid.

A new polymorph of deoxycholic acid (DCA) was formed by using a supercritical carbon dioxide treatment. Deoxycholic acid crystals were stored in a pressure vessel purged with carbon dioxide at 12MPa, 60 degrees C for definite intervals. After storage for 1h in supercritical carbon dioxide (SC-CO2), new X-ray diffraction (XRD) peaks, not found in the bulk DCA crystal, were observed at 2theta = 7.4 degrees, 9.7 degrees and 14.0 degrees. The intensities of the new diffraction peaks increased with an increase in storage time, whereas the intensities of the diffraction peaks due to bulk DCA crystal decreased. On the DSC curves, the crystals obtained showed an exothermic peak at around 155 degrees C followed by the melting peak of bulk DCA crystal at 175 degrees C. By the temperature-controlled powder XRD measurement, the crystals obtained were found to be a metastable form of DCA. The polymorphs of DCA have not been reported; therefore, the SC-CO2 treatment would be a peculiar method to obtain a DCA polymorph.

Carbon Dioxide↗

PubMed2003

Factors affecting the apparent solubility of ursodeoxycholic acid in the grinding process.

Ursodeoxycholic acid (UDCA) was ground by a vibrating mill. Apparent solubility of the ground sample was determined by Coulter counter method. The samples were characterized by pore size distribution measurement, powder X-ray diffraction (PXRD) measurement, near infra-red (NIR) spectroscopy and contact angle measurement. The dispersive and polar components of surface free energy were calculated from the contact angle data determined by a contact angle analyzer. Surface polarity was calculated from the surface free energy components. The apparent solubility of UDCA was increased by the grinding with vibrating mill, however, the particle size of ground sample was not decreased. An amorphization was observed in the PXRD pattern of the ground sample, and the crystallinity of sample was decreased with increasing the grinding time. During the initial grinding, the dispersive component of surface free energy was decreased, whereas the polar part of surface free energy was increased. The surface polarity of the sample was increased in the same manner. Relationship between the solubility and the factors changing in the grinding process was evaluated. There was a significant correlation between the apparent solubility and the surface polarity and crystallinity of the sample. The NIR spectra confirmed the appearance of [bond]OH group on the sample surface. The apparent solubility increase of the ground sample was closely related to the improvement of the surface polarity and the destruction of crystalline structure.

Crystallization↗

PubMed2003

Differentiated thermal crystallization from amorphous chenodeoxycholic acid between the ground specimens derived from the polymorphs.

Crystallization behavior of amorphous chenodeoxycholic acid (CDCA) was studied using X-ray diffraction (XRD), infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The two polymorphs of CDCA, form I (mp 166 degrees C) and form III (mp 119 degrees C), were ground with a vibrational mill. The ground samples of both crystal forms showed halo X-ray diffraction patterns. DSC curves of the amorphous samples derived from the form I and form III showed exothermic peaks due to the crystallization to the form I at 120 and 147 degrees C, respectively. When the ground form III was mixed with the ground form I, the crystallization temperature shifted to a lower temperature as the content of the ground form I increased. In the case of co-ground sample of form I and form III, the crystallization to form I crystals proceeded by two different modes. These results indicate that the physicochemical state was different among the ground samples of the form I and form III, and that the crystal nuclei played an important role on the crystallization process of the amorphous CDCA.

Calorimetry, Differential Scanning↗

PubMed2003

Adsorption and entrapment of salicylamide molecules into the mesoporous structure of folded sheets mesoporous material (FSM-16).

PURPOSE: The aim of this study was to estimate the molecular state of salicylamide on the surface of mesoporous silicas and to investigate the dissolution behavior of salicylamide from the solid dispersion. METHODS: Folded sheets mesoporous material (FSM-16) were used as a porous material. The molecular state of salicylamide was estimated by powder X-ray diffractometry, infrared spectroscopy, and fluorescence spectroscopy. RESULTS: The molecular state of salicylamide can be changed by simple blending with FSM-16. When a physical mixture of 25% salicylamide and 75% FSM-16 was heated at 120 degrees C for 3 h, amorphization of salicylamide was observed from the powder X-ray diffraction pattern. The fluorescence emission peak of salicylamide at 433.5 nm shifted to a longer wavelength of 447.5 nm after heating. Changes in fluorescence decay curve suggested that salicylamide molecules were dispersed into the hexagonal FSM-16 channels during the heating process. Enhanced dissolution in the initial stage of salicylamide from the sealed heated sample was observed in comparison with salicylamide crystals. CONCLUSIONS: Heat treatment of a physical mixture of salicylamide with FSM-16 gave a solid dispersion in which the salicylamide molecules changed to an amorphous state by adsorption onto the FSM-16 channels. Amorphization of salicylamide contributed to the improvement of dissolution.

Calorimetry, Differential Scanning↗

PubMed2003

Nanoparticle formation of poorly water-soluble drugs from ternary ground mixtures with PVP and SDS.

Poorly water-soluble drugs N-5159, griseofulvin (GFV), glibenclamide (GBM) and nifedipine (NFP) were ground in a dry process with polyvinylpyrrolidone (PVP) and sodium dodecyl sulfate (SDS). Different crystallinity behavior of each drug during grinding was shown in the ternary Drug/PVP/SDS system. However, when each ternary Drug/PVP/SDS ground mixture was added to distilled water, crystalline nanoparticles which were 200 nm or less in size were formed and had excellent stability. Zeta potential measurement suggested that the nanoparticles had a structure where SDS was adsorbed onto the particles that were formed by the adsorption of PVP on the surface of drug crystals. Stable existence of crystalline nanoparticles was attributable to the inhibition of aggregation caused by the adsorption of PVP and SDS on the surface of drug crystals. Furthermore, the electrostatic repulsion due to the negative charge of SDS on a shell of nanoparticles could be assumed to contribute to the stable dispersion.

Chemistry, Pharmaceutical↗

PubMed2003

Novel channel structure of bile acid-guest inclusion complex formed between ursodeoxycholic acid and phenanthrene.

The crystal structure of inclusion complex between ursodeoxycholic acid (UDCA), and phenanthrene has been determined. UDCA molecules formed hydrogen bond network to provide the channel structure along b axis, and phenanthrene molecules were accommodated in the cavity with a stoichiometry of 1 : 1 molar ratio. The channel structure observed in the UDCA-phenanthrene complex was significantly different from that of inclusion complex previously reported for deoxycholic acid (DCA) and cholic acid (CA). Because of the mesh-like hydrogen bond network, channel framework of UDCA could have less flexibility than that of DCA and CA. The difference of molecular state of phenanthrene was clearly observed in solid-state fluorescence measurement.

Bile Acids and Salts↗

PubMed2003

Improvement of physicochemical properties of N-4472. Part III. VC/N-4472 complex formation and self-association in aqueous solution.

To improve the aqueous solubility of a poorly water-soluble drug, N-[2-(3,5-di-tert-butyl-4-hydroxyphenethyl)-4,6-difluorophenyl]-N'-[4-(N-benzylpiperidyl)]urea (N-4472), organic acid/N-4472 evaporates were prepared by using succinic acid, L-tartaric acid, citric acid and L-ascorbic acid (VC). Among these evaporates, only the VC/N-4472 evaporate at a molar ratio of more than 2 (VC/N-4472) formed stable colloidal particles (with a mean particle size <or=100 nm) in aqueous solution. In particular, the evaporate prepared at the molar ratio of 5 (VC/N-4472) formed a clear solution comprising fine particles with a narrow particle size distribution of 8-15 nm. On the basis of surface tension measurement, zeta potential determination and static light scattering measurement, it was conceivable that both N-4472 and VC contributed to the formation of a surface-active complex in aqueous solution, while the colloidal particles could be interpreted as the self-association product of these complexes. According to the findings on (1)H-NMR and attenuated total reflectance Fourier transform infrared spectra, it was postulated that upon combining both components at a molar ratio of 2 (VC/N-4472), a 1 : 1 association complex of N-4472 and VC was formed, whereas the higher order complexes were assumed formed with use of a molar ratio of more than 2 (VC/N-4472). Furthermore, it was evidenced that all of these complexes were composed of amphiphilic structures comprising both hydrophobic N-4472 moiety and hydrophilic VC moiety, thereby properly accounting for surface-active property of these complexes.

Acids↗