Kunikazu Moribe

Chiba University, Tiba, Chiba, Japan

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Publications (87)233.78 Total impact

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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; · 2.61 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):B171-B175. · 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. · 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; · 3.99 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; · 3.99 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; · 3.99 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.
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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; · 4.57 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; · 3.99 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; · 4.57 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 07/2013; · 3.13 Impact Factor
  • ECS Transactions 03/2013; 50(12):109-116.
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    ABSTRACT: Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.
    Current pharmaceutical design 03/2013; · 4.41 Impact Factor
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    ABSTRACT: The aim of this study was to confirm whether light anhydrous silicic acid (Aerosil) could exhibit a stabilizing effect on the physical stability of solid dispersion under humidified conditions. Ternary solid dispersions consist of 50% troglitazone, and various ratios of polyvinyl pyrrolidone and Aerosil were prepared using the co-milling method and then evaluated for their crystallizing behavior under storage conditions. The results showed that Aerosil has a stabilizing effect against crystallizing in the dihydrate of troglitazone under humidified conditions and has an appropriate ratio range (Troglitazone/PVP/Aerosil = 50/30–20/20–30) in the ternary solid dispersion, when considering total quality satisfaction such as physical stability and dissolution. Furthermore, it was found that hydrophobized Aerosil R805 has a stronger stabilizing effect than hydrophilic Aerosil 200. The stabilizing mechanism was discussed based on the comparative results and possible molecular interaction.
    Advanced Powder Technology 01/2013; · 1.64 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate quantitatively the effects of fluoride on the solubility and crystallinity of carbonated apatites (CAPs) after its incorporation into the crystal lattice using the metastable equilibrium solubility (MES) distribution method. Fluoride-incorporated CAPs (F-CAPs) of two different carbonate levels (3 and 5%) and fluoride contents from 0 to 20,000 µg/g were synthesized. X-ray diffraction experiments and Rietveld analysis were conducted to obtain crystallite microstrain and unit cell parameters. Acetate buffer MES solution media were prepared at two solution fluoride concentrations (0.2 and 2.0 mg/l) and at two pHs (5.0 and 5.7). The unit cell a-axis values of the F-CAPs were found to decrease as the fluoride content increased, consistent with the fluoride being incorporated into the crystal lattice. The fluoride concentrations in the MES solution media were high enough to provide a 'swamping' effect such that the fluoride released from the F-CAPs during dissolution was minimal in changing the solution fluoride concentration. Employing the MES distribution superposition method, it was shown that the surface complex possessing the fluorapatite (FAP) stoichiometry [Ca(10)(PO(4))(6)F(2)] accounted for the MES distribution behavior of all experiments. In addition, the mean pI(FAP) [the value of -log(a(Ca)(10)a(PO)((4))(6)a(F)(2)) calculated from the ionic activity product based on FAP stoichiometry of the MES dissolution media in which 50% of the F-CAPs had dissolved] correlated well with the crystallite microstrain parameters of the F-CAPs. The incorporated fluoride in the F-CAPs showed only modest effects on F-CAP crystallinity and solubility.
    Caries Research 12/2012; 47(3):193-202. · 2.50 Impact Factor
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    ABSTRACT: A solid dispersion (SPD) of carbamazepine (CBZ) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) was prepared by the spray drying method. The apparent solubility (37 °C, pH 7.4) of CBZ observed with the SPD was over 3 times higher than the solubility of unprocessed CBZ. The supersaturated solution was stable for 7 days. A higher concentration of CBZ in aqueous medium was also achieved by mixing with Poloxamer 407 (P407), a solubilizing agent. From permeation studies of CBZ using Caco-2 monolayers and dialysis membranes, we observed improved CBZ permeation across the membrane in the supersaturated solution of CBZ/HPMC-AS SPD. On the contrary, the CBZ-solubilized P407 solution exhibited poor permeation by CBZ. The chemical shifts of CBZ on the (1)H NMR spectrum from CBZ/HPMC-AS SPD solution were not altered significantly by coexistence with HPMC-AS. In contrast, an upfield shift of CBZ was observed in the CBZ/P407 solution. The spin-lattice relaxation time (T(1)) over spin-spin relaxation time (T(2)) indicated that the mobility of CBZ in the HPMC-AS solution was much lower than that in water. Meanwhile, the mobility of CBZ in P407 solution was significantly higher than that in water. NMR data indicate that CBZ does not strongly interact with HPMC-AS. CBZ mobility was suppressed due to self-association and microviscosity around CBZ, which do not affect permeation behavior. Most of the CBZ molecules in the CBZ/P407 solution were solubilized in the hydrophobic core of P407, and a few were free to permeate the membrane. The molecular state of CBZ, as evaluated by NMR measurements, directly correlated with permeation behavior.
    Molecular Pharmaceutics 09/2012; · 4.57 Impact Factor
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    ABSTRACT: Transglycosylated rutin (Rutin-G), a newly developed transglycosylated food additive, was used as a novel excipient for improving the dissolution and absorption properties of flurbiprofen. No surface activity was found up to 100mg/mL of Rutin-G concentration. No cytotoxicity to Caco-2 cells was observed even at a high level of 100mg/mL Rutin-G solution. (1)H NMR study with concentration variation revealed that Rutin-G formed small aggregates in water, with the aggregation number of Rutin-G above the critical aggregation concentration of about 5.0mg/mL being 4. Structural analyses by small-angle X-ray scattering determined the aggregate to be several nanometers in maximum length. A solubility test of flurbiprofen in the presence of Rutin-G showed that the amount of dissolved flurbiprofen increased in proportion to the amount of Rutin-G loaded. This finding indicated a stoichiometric relationship between flurbiprofen and Rutin-G. The spray-dried particles of flurbiprofen/Rutin-G showed a significantly higher dissolution rate and greater absorption profile compared with the commercial flurbiprofen powder. Taken together, the results indicate the potential application of Rutin-G in the formation of a novel nanostructure of drug/transglycosylated material.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2012; 82(1):120-6. · 3.15 Impact Factor
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    ABSTRACT: Indomethacin (IMC) nanoparticles were formed by cogrinding with dextrin under defined moisture conditions. We investigated the mechanism by which IMC nanoparticles are formed and the factors affecting their formation. Cogrinding of IMC and dextrin with optimal water content yielded more than 60% nanoparticles with an average size of 100–200 nm in aqueous solution. Mixtures ground in dry or higher moisture conditions yielded a lower proportion of IMC nanoparticles. The water content producing maximum yields of nanoparticles varied depending on the weight ratio of dextrin to IMC, and the molecular weight of dextrin. Powder X-ray diffraction and solid-state NMR measurements demonstrated that the molecular state of IMC in ground mixture (GM) of IMC and dextrin at suitable moisture condition was mostly crystalline, while that of GM at dry condition was a mixture of amorphous and crystalline forms. The morphology of nanoparticles observed by atomic force microscopy in aqueous solution was soft at the outer surface, suggesting dextrin may adsorb on the IMC nanocrystal surface. Water during grinding could facilitate the dispersion of nanocrystalline IMC into the dextrin matrix. The effective adsorption and interaction of dextrin on the IMC nanocrystal surface could inhibit the aggregation after dispersing in water.
    Powder Technology 05/2012; 221:213–219. · 2.27 Impact Factor
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    ABSTRACT: Physicochemical characterization and structural evaluation of a 2:1 naproxen-nicotinamide cocrystal were performed. The 2:1 cocrystal showed rapid naproxen dissolution and less water vapor adsorption, indicating better pharmaceutical properties of naproxen. The unique 2:1 cocrystal formation was evaluated by solid-state nuclear magnetic resonance (NMR). The assignments of all H and (13) C peaks for naproxen and the cocrystal were performed using dipolar-insensitive nuclei enhanced by polarization transfer and (1) H-(13) C cross-polarization (CP)-heteronuclear correlation (HETCOR) NMR measurements. The (13) C chemical shift revealed that two naproxen molecules and one nicotinamide molecule existed in the asymmetric unit of the cocrystal. The (1) H chemical shifts indicated that the carboxylic group of the naproxen in the cocrystal was nonionized, and the CH-π interaction between naproxens was very strong. From the (1) H-(13) C CP-HETCOR NMR spectrum with contact time of 5 ms, two different synthons, carboxylic acid-amide and carboxylic acid-pyridine ring, were found between naproxen and nicotinamide. Single-crystal X-ray analysis, which supported the solid-state NMR results, clarified the geometry and intermolecular interactions in more detail. The structure is unique among pharmaceutical cocrystals because each carboxyl group of the two naproxens formed different intermolecular synthons.
    Journal of Pharmaceutical Sciences 04/2012; 101(9):3214-21. · 3.13 Impact Factor

Publication Stats

536 Citations
233.78 Total Impact Points


  • 2003–2014
    • Chiba University
      • Graduate School of Pharmaceutical Sciences
      Tiba, Chiba, Japan
  • 2012
    • Osaka University of Pharmaceutical Sciences
      Gihu, Gifu, Japan
    • Shionogi & Co., Ltd.
      Ōsaka, Ōsaka, Japan
  • 2011
    • Josai University
      Saitama, Saitama, Japan
  • 2009
    • Daiichi Sankyo Company
      • Formulation Technology Research
      Tokyo, Tokyo-to, Japan
  • 2008
    • Astellas Pharmaceutical
      Northbrook, Illinois, Japan
    • Chugai pharmceutical
    • Mahidol University
      • Department of Manufacturing Pharmacy
      Bangkok, Bangkok, Thailand
  • 2004–2006
    • University of Yamanashi
      • • Faculty of Medicine
      • • Department of Pharmacy
      Kōhu, Yamanashi, Japan