Kunikazu Moribe

Chiba University, Tiba, Chiba, Japan

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Publications (97)256.45 Total impact

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    ABSTRACT: The chemical stability of suplatast tosilate (ST) was evaluated under dry conditions at 60 °C, with a focus on the polymorphic forms and crystal uniformity. The intact α-form, namely α-C type crystals, was crystallized rapidly by adding isopropyl ether into an ethanolic solution of ST. The α-C type crystals exhibited low stability at 60 °C. In addition to the α-C type crystals, two types of α-form crystals with different uniformities, namely α-A and α-B type crystals, were prepared. The α-A type crystals were prepared by conversion from the η-form in aqueous acetone, while the α-B type crystals were prepared by recrystallization from 2-propanol at a low supersaturation level. The stability of the α-form crystals was as follows: α-A > α-B > α-C. The uniformity of ST crystals was determined according to the newly developed high performance liquid chromatography (HPLC) method. The α-C type crystals exhibited inferior chemical stability due to unstable crystalline phases. They showed preferential enrichment and exhibited a unique optical resolution phenomenon. The observed unstable crystalline phases were produced during the crystallization process. α-A type crystals, which had high regularity, exhibited excellent stability. Overall, we prepared and evaluated the structures of α-form crystals with different uniformities.
    Journal of Drug Delivery Science and Technology 06/2015; 27. DOI:10.1016/j.jddst.2015.04.004 · 1.09 Impact Factor
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    ABSTRACT: A variable-temperature 1H NMR study was performed to investigate the effects of the molecular weight of poly(ethylene glycol) (PEG) in PEG-lipids and cholesterol addition to the lipid bilayer on PEG chain flexibility at the liposomal surface. PEG-lipids, i.e., l-α-distearoylphosphatidylethanolamine (DSPE)-PEG, with PEG molecular weights of 750, 2000, and 5000 were modified to liposomes of ca. 100 nm. The 1H NMR peak of PEG in DSPE-PEG was overlapped by broad and sharp peaks, corresponding to rigid and flexible PEG components, respectively. When the PEG molecular weight was increased, the PEG peak became sharp, indicating that long-chain PEGs were more flexible on the liposome surface. The proportion of flexible components projecting into the water phase increased as the PEG chain length increased. Peak sharpening also occurred when the cholesterol content was increased from 0 to 30 mol%, demonstrating that cholesterol incorporation into the lipid bilayer enhanced the PEG chain flexibility. In addition, the PEG chain flexibility significantly increased when cholesterol was delocalized in the lipid bilayer at concentrations above 20 mol%. Lateral diffusion of the lipid with the presence of cholesterol in the lipid bilayer significantly affected the PEG chain flexibility.
    Colloids and Surfaces A Physicochemical and Engineering Aspects 06/2015; 474. DOI:10.1016/j.colsurfa.2015.03.006 · 2.35 Impact Factor
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    ABSTRACT: A nanosuspension of piroxicam (PXC) and poloxamer 407 (poloxamer) prepared by the wet milling method was directly evaluated at the molecular level from the viewpoint of both solution and solid phases. (13)C solution-state NMR measurements revealed a reduction in the concentration of dissolved poloxamer in the nanosuspension. Furthermore, the fraction of dissolved polyethylene oxide (PEO) chain, which is the hydrophilic part of poloxamer, was higher than that of dissolved polypropylene oxide (PPO) chain, the hydrophobic part. (13)C suspended-state NMR and Raman spectroscopies detected both solid-state PXC and poloxamer involved in the nanoparticles. Interestingly, the coexistence of crystalline and amorphous PXC in the nanoparticle was demonstrated. The yellow color of the nanosuspension strongly supported the existence of amorphous PXC. Changes in the peak intensity depending on the contact time in the suspended-state NMR spectrum revealed that the PEO chain of poloxamer in the nanoparticle had higher mobility compared with the PPO chain. The PEO chain should project into the water phase and form the outer layer of the nanoparticles, whereas the PPO chain should face the inner side of the nanoparticles. Amorphous PXC could be stabilized by intermolecular interaction with the PPO chain near the surface of the nanoparticles, whereas crystalline PXC could form the inner core.
    Molecular Pharmaceutics 04/2015; 12(5). DOI:10.1021/mp500872g · 4.79 Impact Factor
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    ABSTRACT: The maintenance mechanism of the supersaturated state of poorly water-soluble drugs, glibenclamide (GLB) and chlorthalidone (CLT), in hydroxypropyl methylcellulose acetate succinate (HPMC-AS) solution was investigated at a molecular level. HPMC-AS suppressed drug crystallization from supersaturated drug solution and maintained high supersaturated level of drugs with small amount of HPMC-AS for 24 h. However, the dissolution of crystalline GLB into HPMC-AS solution failed to produce supersaturated concentrations, although supersaturated concentrations were achieved by adding amorphous GLB to HPMC-AS solution. HPMC-AS did not improve drug dissolution and/or solubility but efficiently inhibited drug crystallization from supersaturated drug solutions. Such an inhibiting effect led to the long-term maintenance of the amorphous state of GLB in HPMC-AS solution. NMR measurements showed that HPMC-AS suppressed the molecular mobility of CLT depending on their supersaturation level. Highly supersaturated CLT in HPMC-AS solution formed a gel-like structure with HPMC-AS, in which the molecular mobility of the CLT was strongly suppressed. The gel-like structure of HPMC-AS could inhibit the reorganization from drug prenuclear aggregates to the crystal nuclei and delay the formation of drug crystals. The prolongation subsequently led to the redissolution of the aggregated drugs in aqueous solution and formed the equilibrium state at the supersaturated drug concentration in HPMC-AS solution. The equilibrium state formation of supersaturated drugs by HPMC-AS should be an essential mechanism underlying the marked drug concentration improvement.
    Molecular Pharmaceutics 02/2015; 12(4). DOI:10.1021/mp500588x · 4.79 Impact Factor
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    ABSTRACT: The purpose of this study was to characterize the non-aqueous nanosuspension of a hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin was used as the model hydrophilic drug. The non-aqueous nanosuspensions were prepared by grinding riboflavin with zirconia beads using eight non-aqueous bases. The mean particle size of riboflavin in the suspensions ranged from 206 to 469 nm, as determined by the dynamic light scattering method. Among the well-dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected for evaluation of the drug permeability through rat skin. The cumulative amount and permeation rate of riboflavin from the nanosuspension were approximately three times higher than those for unprocessed riboflavin in oleic acid. Fluorescence imaging of the riboflavin nanosuspension suggested improved penetration of riboflavin into the stratum corneum. Furthermore, the addition of polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared in oleic acid markedly improved the riboflavin dispersibility. These results show that the preparation of a nanosuspension in a non-aqueous base by bead milling is one of the simple methods to improve the skin permeability of hydrophilic drugs.
    CHEMICAL & PHARMACEUTICAL BULLETIN 01/2015; 63(2):88-94. DOI:10.1248/cpb.c14-00641 · 1.38 Impact Factor
  • Journal of Drug Delivery Science and Technology 12/2014; DOI:10.1016/S1773-2247(14)50135-9 · 1.09 Impact Factor
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    ABSTRACT: Two polymorphic forms of a sulfathiazole (STZ):oxalic acid (OXA) 1:1 complex were successfully prepared by different cogrinding methods and characterized by multiple analytical techniques. Rod-milled and ball-milled ground mixtures had different powder X-ray diffraction patterns, showing polymorph formation of the STZ-OXA complex (complex A and complex B). The heat of fusion from differential scanning calorimetry curves and terahertz time-domain spectra helped differentiating the polymorphs. According to infrared spectra, C-13 NMR chemical shifts, and the relative intensities of N-15 NMR peaks, both polymorphs were salts where the proton of a -COOH group in OXA was transferred to a -NH2 group in STZ. High-resolution H-1 NMR and H-1-C-13 heteronuclear correlation NMR spectra indicated that complex B in powder form had a cocrystal type structure compared to complex A having a clathrate-type structure. Complex B structure suggested by solid-state NMR coincided well with the experimentally determined one, which was formed from three layers of thiazole rings, benzene rings, and OXAs, by using single-crystal X-ray diffraction (SC-XRD) measurement. Advanced solid-state NAIR spectroscopy measurements was useful to elucidate the structure of a polymorph, for which SC-XRD data are not available, by referring to the SC-XRD data of another polymorph.
    Crystal Growth & Design 09/2014; 14(9):4510-4518. DOI:10.1021/cg5005903 · 4.56 Impact Factor
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    ABSTRACT: The effects of drug-crystallization inhibitor in bile acid/lipid micelles solution on drug permeation was evaluated during the drug crystallization process. Hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was used as a drug-crystallization inhibitor, which efficiently suppressed dexamethasone (DEX) crystallization in a gastrointestinal fluid model containing sodium taurocholate (NaTC) and egg-phosphatidylcholine (egg-PC). Changes of molecular state of supersaturated DEX during the DEX crystallization process was monitored in real time using proton nuclear magnetic resonance ((1)H NMR). It revealed that DEX distribution to bulk water and micellar phases formed by NaTC and egg-PC was not changed during the DEX crystallization process even in the presence of HPMC-AS. DEX permeation during DEX crystallization was evaluated using dissolution/permeability system. The combination of crystallization inhibition by HPMC-AS and DEX micellar encapsulation led to considerably higher DEX concentrations and improvement of DEX permeation at the beginning of the DEX crystallization process. Crystallization inhibition by HPMC-AS can efficiently work even in the micellar solution, where NaTC/egg-PC micelles encapsulates some DEX. It was concluded that a crystallization inhibitor contributed to improvement of permeation of a poorly water-soluble drug in gastrointestinal fluid.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 06/2014; DOI:10.1016/j.ejps.2014.06.007 · 3.01 Impact Factor
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    ABSTRACT: Molecular networks based on noncovalent bonds have resonant frequencies in the terahertz (THz) region. THz spectroscopy is a powerful tool for identifying molecular bonds, such as intermolecular or intramolecular hydrogen bonds, in pharmaceuticals. A THz chemical imaging (TCI) system was developed by combining a THz time-domain spectrometer with a translational stage to obtain two-dimensional distributions of molecular networks in tablet samples. Since THz spectral peaks of pharmaceuticals are broad at room temperature, multicomponent chemical analysis with the TCI system has some limitations. In this paper, we describe multicomponent chemical analysis of pharmaceuticals using a sample chamber cooled by a cryostat. TCI measurement at low temperature sharpens spectral peaks and/or shifts peak frequencies, enabling us to determine the distribution of several kinds of pharmaceuticals in a tablet. The TCI system provides THz images of polymorphic form distribution of famotidine binding with D-mannitol in an over-the-counter pharmaceutical tablet. Furthermore, the molecular mechanics method was used to determine the vibrational modes of the peaks in the spectra of famotidine polymorphic forms.
    Journal of The Electrochemical Society 05/2014; 161(9-9):B171-B175. DOI:10.1149/2.0201409jes · 2.86 Impact Factor
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    ABSTRACT: Eleven guest drugs with planar structures were incorporated into the intermolecular spaces between polyethylene glycol/γ-cyclodextrin (γ-CD)-polypseudorotaxanes by a sealed-heating method. Drug incorporation changed the crystal packing of γ-CD from hexagonal- to monoclinic-columnar forms, without dependence on the guest species. The incorporation of guest drugs was size dependent and stoichiometric. Guest drugs with one benzene ring and maximum cross sectional areas of ca. 40–55 Å2 exhibited a drug to γ-CD stoichiometry of 2:1. Meanwhile, the stoichiometry was 1:1 for drugs with 2–3 benzene rings and maximum cross sectional areas of ca. 60–75 Å2. More sterically bulky drugs (four and five benzene rings) did form complexes, though the complexation efficiency was insufficient to form stoichiometric complexes, due to steric hindrance. The volume of intermolecular space of the host was estimated to be larger than that of a β-CD cavity and as large as that of a γ-CD cavity. Hydrophobic and van der Waals interactions worked as driving forces for the complexation because polycyclic aromatic hydrocarbons with high log P values formed the complex. The dissolution property of the hydrophobic pharmaceutical drug naproxen was clearly improved by the complexation because naproxen existed in a monomolecular state in the complex.
    Crystal Growth & Design 05/2014; 14(6):2773–2781. DOI:10.1021/cg401934v · 4.56 Impact Factor
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    ABSTRACT: Hydrocortisone (HC), a poorly water-soluble drug, was encapsulated within organic nanotubes (ONTs), which were formed via the self-assembly of N-{12-[(2-α,β-d-glucopyranosyl) carbamoyl]dodecanyl}-glycylglycylglycine acid. The stability of the ONTs was evaluated in ten organic solvents, of differing polarities, by field emission transmission electron microscopy. The ONTs maintained their stable tubular structure in the highly polar solvents, such as ethanol and acetone. Furthermore, solution-state (1)H-NMR spectroscopy confirmed that they were practically insoluble in acetone at 25°C (0.015mg/mL). HC-loaded ONTs were prepared by solvent evaporation using acetone. A sample with a 3/7 weight ratio of HC/ONT was analyzed by powder X-ray diffraction, which confirmed the presence of a halo pattern and the absence of any crystalline HC peak. HC peak broadening, observed by solid-state (13)C-NMR measurements of the evaporated sample, indicated the presence of HC crystals. These results indicated that HC was successfully encapsulated in ONT as an amorphous state. Improvements of the HC dissolution rate were clearly observed in aqueous media at both pH 1.2 and 6.8, probably due to HC amorphization in the ONTs. Phenytoin, another poorly water-soluble drug, also showed significant dissolution improvement upon ONT encapsulation. Therefore, ONTs can serve as an alternative pharmaceutical excipient to enhance the bioavailability of poorly water-soluble drugs.
    International Journal of Pharmaceutics 04/2014; 469(1). DOI:10.1016/j.ijpharm.2014.04.005 · 3.79 Impact Factor
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    ABSTRACT: We investigated the drug solubilization mechanism of α-glucosyl stevia (Stevia-G) which was synthesized from stevia (rebaudioside-A) by transglycosylation. (1)H and (13)C NMR peaks of Stevia-G in water were assigned by two-dimensional (2D) NMR experiments including (1)H-(1)H correlation, (1)H-(13)C heteronuclear multiple bond correlation, and (1)H-(13)C heteronuclear multiple quantum coherence spectroscopies. The (1)H and (13)C peaks clearly showed the incorporation of two glucose units into rebaudioside-A to produce Stevia-G, supported by steviol glycoside and glucosyl residue assays. The concentration-dependent chemical shifts of Stevia-G protons correlated well with a mass-action law model, indicating the self-association of Stevia-G molecules in water. The critical micelle concentration (CMC) was 12.0mg/mL at 37°C. The aggregation number was 2 below the CMC and 12 above the CMC. Dynamic light scattering and 2D (1)H-(1)H nuclear Overhauser effect spectroscopy (NOESY) NMR experiments demonstrated that Stevia-G self-associated into micelles of a few nanometers in size with a core-shell structure, containing a kaurane diterpenoid-based hydrophobic core and a glucose-based shell. 2D (1)H-(1)H NOESY NMR measurements also revealed that a poorly water-soluble drug, naringenin, was incorporated into the hydrophobic core of the Stevia-G micelle. The Stevia-G self-assembly behavior and micellar drug inclusion capacity can achieve significant enhancement in drug solubility.
    International Journal of Pharmaceutics 02/2014; 465(1-2). DOI:10.1016/j.ijpharm.2014.01.035 · 3.79 Impact Factor
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    ABSTRACT: The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H-NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used.
    International Journal of Pharmaceutics 01/2014; DOI:10.1016/j.ijpharm.2014.01.005 · 3.79 Impact Factor
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    ABSTRACT: In this study, using mesoporous silica for the solubility enhancement of poorly water-soluble drug was investigated. Although the incorporating drug into mesoporous silica is generally performed through the solvent method, the new melting method was proposed in the present study. Fenofibrate, a poorly water-soluble drug, was incorporated into mesoporous silica by solvent method and melting method. The obtained samples were observed by SEM and their physicochemical properties were evaluated by PXRD and DSC measurement. The dissolution and supersaturated property were also investigated. The results from SEM, PXRD and DSC measurement showed that drug could be loaded into pore via the melting method as well as by the solvent method. The drug loaded quantity depended on the pore volume. Drug up to 33% could be incorporated into mesoporous silica and existed in amorphous state. When drug was overloaded or difficulty in incorporation into pore was found, recrystallization of drug occurred at the outer surface of mesoporous silica. From the dissolution test, samples prepared by solvent method and melting method gave the supersaturated drug concentration which sample from melting method showed superior dissolution to the one from solvent method. From this study, drug was efficiently incorporated into mesoporous silica by the melting method which is a simple and solvent-free process, and the aqueous solubility enhancement of poorly water-soluble drug was achieved.
    Asian Journal of Pharmaceutical Sciences 12/2013; 8(6):329–335. DOI:10.1016/j.ajps.2013.11.001
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    ABSTRACT: The intermolecular interaction between mefenamic acid (MFA), a poorly water-soluble non-steroidal anti-inflammatory drug, and Eudragit® EPO (EPO), a water-soluble polymer, is investigated in their supersaturated solution using high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy. The stable supersaturated solution with a high MFA concentration of 3.0 mg/mL is prepared by dispersing the amorphous solid dispersion into a d-acetate buffer at pH 5.5 and 37 ºC. By virtue of MAS at 2.7 kHz, the extremely broad and unresolved 1H resonances of MFA in one-dimensional 1H NMR spectrum of the supersaturated solution are well resolved, thus enabling the complete assignment of MFA 1H resonances in the aqueous solution. Two-dimensional (2D) 1H/1H nuclear Overhauser effect spectroscopy (NOESY) and radio frequency-driven recoupling (RFDR) under MAS conditions reveal the interaction of MFA with EPO in the supersaturated solution at an atomic level. The strong cross-correlations observed in the 2D 1H/1H NMR spectra indicate a hydrophobic interaction between the aromatic group of MFA and the backbone of EPO. Furthermore, the aminoalkyl group in the side chain of EPO forms a hydrophilic interaction, which can be either electrostatic or hydrogen bonding, with the carboxyl group of MFA. We believe these hydrophobic and hydrophilic interactions between MFA and EPO molecules play a key role in the formation of this extremely stable supersaturated solution. In addition, 2D 1H/1H RFDR demonstrates that the molecular MFA-EPO interaction is quite flexible and dynamic.
    Molecular Pharmaceutics 11/2013; DOI:10.1021/mp4005723 · 4.79 Impact Factor
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    ABSTRACT: We found four new polymorphic forms (γ-, ɛ-, ζ-, and η-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (α-, β-, and δ-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the ɛ- and η-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the ɛ- and η-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The α-form was the most insoluble in 2-propanol at 35°C, and was thus concluded to be the most stable form. The ɛ-form was the most soluble, and a polymorphic transition from the ɛ- to the α-form was observed during solubility testing.
    International Journal of Pharmaceutics 11/2013; DOI:10.1016/j.ijpharm.2013.10.049 · 3.79 Impact Factor
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    ABSTRACT: We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade (LF). 1D-(1)H-NMR measurements showed that the molecular mobility of CBZ was clearly suppressed in the HF solution compared to that in the LF solution. Interaction between CBZ and HF in a supersaturated solution was directly detected using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity obtained using NOESY of HF protons with CBZ aromatic protons was greater than that with the amide proton, which indicated that CBZ had hydrophobic interactions with HF in a supersaturated solution. In contrast, no interaction was observed between CBZ and LF in the LF solution. Saturation transfer difference NMR measurement was used to determine the interaction sites between CBZ and HF. Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS although the interaction with the succinoyl substituent was quite small. The acetyl groups played an important role in the hydrophobic interaction between HF and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the smaller ratio of the succinoyl substituent. This might be responsible for the strong hydrophobic interaction between HF and CBZ. The intermolecular interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly explained the strength of inhibition of HPMC-AS on drug recrystallization.
    Molecular Pharmaceutics 09/2013; 10(10). DOI:10.1021/mp400278j · 4.79 Impact Factor
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    ABSTRACT: We characterized cromolyn sodium (CS) hydrates and evaluated their molecular states in low-dose formulations using Na-multiquantum magic-angle spinning (MQMAS) nuclear magnetic resonance (NMR) analysis. Two CS hydrates, low-water-content hydrated form and high-water-content hydrated form containing 2-3 and 5-6 hydrates, respectively, were prepared by humidification. Single-crystal X-ray diffraction and powder X-ray diffraction analysis revealed that these CS hydrates contained sodium channel structures and that water molecules were adsorbed on the sodium nucleus. (13) C-cross-polarization/MAS NMR spectra of these hydrates revealed similar results, confirming that the water molecules were adsorbed not on the cromolyn skeletons but mainly on the sodium nucleus. In contrast, (23) Na-MQMAS NMR analysis allowed us to clearly distinguish these hydrates without discernible effects from quadrupolar interaction. Thus, MQMAS NMR analysis is a valuable tool for evaluating salt drugs and their formulations. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 08/2013; 102(8). DOI:10.1002/jps.23655 · 3.01 Impact Factor
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    ABSTRACT: Molecular networks based on hydrogen bonds have resonant frequencies in the terahertz (THz) region. THz spectroscopy is a powerful tool for identifying molecular networks created by intermolecular or intra-molecular hydrogen bonds in pharmaceutical and biomedical samples such as drugs, proteins, and cancer cells. A THz chemical imaging (TCI) system was developed by combining a THz time-domain spectrometer with a translational stage to obtain two-dimensional distributions of molecular networks in tablet samples. Since THz spectral peaks of pharmaceuticals are broad at room temperature, multicomponent chemical analysis is limited using the TCI system. In this paper, we describe multicomponent chemical analysis of pharmaceuticals using a sample chamber cooled by a cryostat. TCI measurement at low temperature sharpens spectral peaks and/or shifts peak frequencies, enabling us to determine the distribution of several kinds of pharmaceutical chemicals within a tablet.
    ECS Transactions 03/2013; 50(12):109-116. DOI:10.1149/05012.0109ecst