Yoshinobu Nakai

Bio: Yoshinobu Nakai is an academic researcher from Chiba University. The author has contributed to research in topics: Benzoic acid & Cyclodextrin. The author has an hindex of 19, co-authored 79 publications receiving 943 citations. Previous affiliations of Yoshinobu Nakai include Assiut University & Teikyo University.

Properties of Crystal Water of α-, β-, and γ-Cyclodextrin

Abstract: The water vapor sorption isotherms have been established for α-, β-, and γ-cyclodextrin at 40°C. The powder X-ray diffraction patterns of crystal forms of cyclodextrins stored at various levels of relative humidity (RH) were examined and the results are discussed in terms of the hydration numbers. α-Cyclodextrin hydrate was stable at RH as low as 11%. The water vapor desorption isotherm of β-cyclodextrin showed pronounced hysteresis, which extended to lower RH.The hydrate form of β-cyclodextrin was stable over a wide range of RH in the desorption process, like that of α-cyclodextrin. The crystal form of γ-cyclodextrin 7H2O was obtaiend in addition to the dehydrate form and the 17H2O hydrate form.

New Methods for Preparing Cyclodextrin Inclusion Compounds. I. Heating in a Sealed Container

Abstract: A new method for preparing a solid inclusion compound was developed. A physical mixture of benzoic acid and α-or β-cyclodextrin (CD) or the ground mixture was sealed in a container after adsorbing a definite amount of water vapor, then heated to a temperature ranging from 43 to 142 °C. The results of powder X-ray diffraction and infrared spectroscopy showed that the crystalline inclusion compound was produced when the container was heated at over 70°C. The combining molar ratio of benzoic acid to α-CD in the inclusion compound prepared by this method was higher than that obtained by the coprecipitation method. Physical mixtures of benzoic acid and α-or β-CD were also sealed in a stainless steel vessel under nitrogen gas pressure, then heated to 127 °C. The pressurized samples had a higher combination ratio than the non-pressurized samples.

The Dispersed States of Medicinal Molecules in Ground Mixtures with α- or β-Cyclodextrin

Abstract: Aspirin, benzoic acid and p-hydroxybenzoic acid, all of which form intermolecularly hydrogen-bonded dimer structures in the crystalline form, were ground with α- or β-cyclodextrin. Inclusion compounds were also prepared by the coprecipitation method, except in the case of the aspirin-α-cyclodextrin system. The dispersed state of the medicinal molecules were investigated by analysis of the infrared spectra in the carbonyl stretching regions. It was suggested that the dispersed state of medicinals in the α-cyclodextrin system was different from that in the β-cyclodextrin system. It was assumed that, by grinding, aspirin molecules were included in the cyclodextrin cavity in the β-cyclodextrin system, but were dispersed monomolecularly in the hydrogen-bonded network structure of cyclodextrin in the α-cyclodextrin system. Interaction between medicinals and α- or β-cyclodextrin in aqueous solution was investigated by means of nuclear magnetic resonance studies. The sublimation of p-hydroxybenzoic acid from the ground mixtures or inclusion compounds with α- or β-cyclodextrin systems was determined by thermogravimetry. The effects of cyclodextrin on the hydrolysis of aspirin under acidic conditions were investigated as well.

Solubility Parameter and Dissolution Behavior of Cefalexin Powders with Different Crystallinity

Abstract: The dissolution behavior and the solubility parameters of cefalexin powders of different crystallinity were determined. The maximum concentration of cefalexin in water 35°C increased with decreasing the crystallinity. Partial solubility parameters of cefalexin were fetermined as δd=8.3, δs=10.2 (cal/cm3)1/2 for intact cefalexin and δd=9.6, δs=12.0(cal/cm3)1/2 for the amorphous. The partial solubility parameters of intact samples were the smallest among those of different crystallinity samples. The variation of δs with crystallinity was significantly greater than that of δd. For the estimation of the interaction with water, the inveraction radii were calculated, and the effectiveness of this value was confirmed.

What is the true solubility advantage for amorphous pharmaceuticals

Abstract: Purpose To evaluate the magnitude of the solubility advantage foramorphous pharmaceutical materials when compared to their crystallinecounterpartsMethods The thermal properties of several drugs in their amorphousand crystalline states were determined using differential scanningcalorimetry From these properties the solubility advantage for theamorphous form was predicted as a function of temperature using a simplethermodynamic analysis These predictions were compared to theresults of experimental measurements of the aqueous solubilities of theamorphous and crystalline forms of the drugs at several temperaturesResults By treating each amorphous drug as either an equilibriumsupercooled liquid or a pseudo-equilibrium glass, the solubilityadvantage compared to the most stable crystalline form was predicted to bebetween 10 and 1600 fold The measured solubility advantage wasusually considerably less than this, and for one compound studied indetail its temperature dependence was also less than predicted It wascalculated that even for partially amorphous materials the apparentsolubility enhancement (theoretical or measured) is likely to influencein-vitro and in-vivo dissolution behaviorConclusions Amorphous pharmaceuticals are markedly more solublethan their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simplethermodynamic considerations This appears to be the result of difficulties indetermining the solubility of amorphous materials under trueequilibrium conditions Simple thermodynamic predictions can provide a useful indication of the theoretical maximum solubility advantage foramorphous pharmaceuticals, which directly reflects the driving forcefor their initial dissolution

Strategies to Address Low Drug Solubility in Discovery and Development

Abstract: Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

Effect of the carriers on the microstructure of mango powder obtained by spray drying and its functional characterization

Abstract: This work aimed the induction of crystallization on powder mango juice during the process of spray drying and the correlation of the microstructure of the powder obtained with the functional properties of stickiness and solubility. To perform this work, we used mango juice with 12 °Brix. Before being dehydrated, the juice undertook addition from the following carriers: maltodextrin, gum arabic and starch waxy in the concentration of 12%. The solution also received addition of crystalline cellulose in the concentrations of 0, 3, 6 and 9%. The powder was obtained through the use of a mini-spray dryer of laboratorial scale. Analyses of microstructure, stickiness, hygroscopicity and solubility were performed on the obtained powder. The microstructure analyses showed that the powders of the mango juices obtained through spray drying using the carriers maltodextrin, gum arabic, starch waxy without the addition of cellulose presented surfaces of amorphous particles. The analysis XRD showed that when 3, 6 and 9% of cellulose were added, the particles showed half-crystalline surfaces. The value of stickiness decreased in terms of the concentration of cellulose reaching values of 0.15, 0.22 and 0.11 Kg-f for maltodextrin, gum arabic and starch waxy, respectively. The functional property of solubility is affected when 9% of cellulose is added reaching the values of 72, 71 and 31% for the carriers maltodextrin, gum arabic and starch wax, respectively.