Mar 2010, Volume 4 Issue 1
    

  • Select all
  • Research articles
    Introduction to the special issue of the 2009 International Symposium on Crystal Engineering & Drug Delivery Systems
    Zhijian CHEN, Wei LI,
    2010, 4(1): 1-1. https://doi.org/10.1007/s11705-009-0306-2
    Download PDF
  • Research articles
    Applications of the crystallization process in the pharmaceutical industry
    Sohrab ROHANI
    2010, 4(1): 2-9. https://doi.org/10.1007/s11705-009-0297-z
    Download PDF
    The applications of the crystallization technique in the pharmaceutical industry as a purification and separation process for the isolation and synthesis of pure active pharmaceutical ingredients (API), co-crystals, controlled release pulmonary drug delivery, and separation of chiral isomers are briefly discussed using a few case studies. The effect of process variables and solvent on the polymorphism and morphology of stavudine is discussed. The implementation of external control in the form of feedback and real-time optimal control using cooling and antisolvent crystallization of paracetamol in water-isopropyl alcohol is introduced. Two methods to prepare micron-sized drug particles, namely, micro-crystallization and polymer-coated API-loaded magnetic nanoparticles for pulmonary drug delivery, are discussed. The significance of co-crystals in drug administration is highlighted using the theophylline-nicotinamide co-crystal system. Resolution of chloromandelic acid derivatives, a racemic compound, is achieved using direct crystallization and diastereomeric salts crystallization. The crystal structures of diastereomeric salts of chloromandelic acid and phenylethylamine are determined. The structure comparison between the less soluble and more soluble salts shows that weak interactions such as CH/π interactions and van der Waals forces contribute to chiral recognition when the hydrogen bonding patterns are similar.
  • Research articles
    Developing macromolecular therapeutics: the future drug-of-choice
    Huining HE, Victor C. YANG, Weibing DONG, Junbo GONG, Jingkang WANG,
    2010, 4(1): 10-17. https://doi.org/10.1007/s11705-009-0291-5
    Download PDF
    Macromolecular drugs including peptides, proteins, antibodies, polysaccharides and nucleic acids have been widely used for therapy of major diseases such as carcinoma and AIDS as well as cardiovascular and neurodegenerative disorders among other medical conditions. Due to their unmatched properties of high selectivity and efficiency, macromolecular drugs have been recognized as the drug-of-choice of the future. Since worldwide progress on macromolecular therapeutics still remains in the infant stage and is therefore wide open for equal-ground competition, R&D related to macromolecular drugs should be considered as the main point of focus in China in setting up its strategic plans in pharmaceutical development. In this article, research strategies and drug delivery approaches that should be adopted to enhance the therapeutic effects of macromolecular drugs are reviewed. In addition, comments concerning how to implement such strategies to excel from competition in this challenging research field, such as the design of innovative and highly effective delivery systems of macromolecular drugs with self-owned intellectual property rights, are provided.
  • Research articles
    Structure controlling and process scale-up in the fabrication of nanomaterials
    Chunzhong LI,
    2010, 4(1): 18-25. https://doi.org/10.1007/s11705-009-0305-3
    Download PDF
    Nanotechnology is already having a significant commercial impact, and will very certainly have a much greater impact in the future. The research on process engineering and scale-up will be very important for the commercial production and application of nanomaterials, because the properties and structure of nanomaterials are not only determined by the nucleation and growth process, but also strongly affected by the engineering properties, such as the mixing, the heat and mass transfer, and also the distribution of temperature, concentration, etc. This paper will present some research work in our laboratory on the fabrication of nanomaterials. Based on the chemical engineering principle and methods, many kinds of novel nanomaterials can be synthesized and their structure can be easily controlled through adjusting the parameters of the fluid mixing, and the distribution of temperature, residence time and concentration, etc. By using the micro-mixing, heat and mass transfer and reaction control methods, the host-guest nanocomposites have been assembled and assumed as the novel electroanalytical sensing nanobiocomposite materials. Based on the principles of chemical engineering, the manufacturing technologies for magnetic powders, calcium carbonate, and titanium dioxide have been developed for commercial-scale production, and the largest production scale has reached 15 kt/year.
  • Research articles
    Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices
    Jingtao WANG, Jin ZHANG, Junjie HAN,
    2010, 4(1): 26-36. https://doi.org/10.1007/s11705-009-0292-4
    Download PDF
    The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of microfluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen “smart” materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO3 was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.
  • Research articles
    Polymorphism of pharmaceutical molecules: perspectives on nucleation
    Jie LU, Zhen LI, Xiaolin JIANG,
    2010, 4(1): 37-44. https://doi.org/10.1007/s11705-009-0294-2
    Download PDF
    Polymorphism is a widespread phenomenon observed in more than half of all drug substances. Various polymorphs frequently possess different physical, chemical, mechanical and thermal properties that can profoundly affect the bioavailability, stability and other performance characteristics of the drug. Accordingly, the elucidation of the relationship between the particular polymorph of a pharmaceutical molecule and its functional properties is crucial to select the most suitable polymorph of the pharmaceutical molecule for development into a drug product. This review briefly introduces recent advances in the discovery and control of the polymorphs of pharmaceutical molecules, in terms of the enhancement of the selective nucleation of a particular polymorph. In the light of this, some cases discussed in the following is to be considered controversial.
  • Research articles
    Synthesis and electrocatalytic property of cubic and spherical nanoparticles of cobalt platinum alloys
    Xiaowei TENG, Hong YANG,
    2010, 4(1): 45-51. https://doi.org/10.1007/s11705-009-0308-0
    Download PDF
    This paper describes the morphological control and electrocatalytic property of CoPt nanoparticles. Both cubic and spherical CoPt nanoparticles were made using cobalt carbonyl and platinum 2,4-pentanedionate under different reaction temperatures in the presence of capping reagents, which included adamantanecarboxylic acid and hexadecylamine. Effects of heterogeneous species on shape of the CoPt nanoparticles were examined by replacing cobalt carbonyl with silver acetylacetonate. Our results suggest that the formation of different shapes of CoPt particles could be attributed to the affinity between cobalt and platinum, and the effects of capping agents. The size and shape dependent electrocatalytic properties of these nanoparticles were examined based on the direct methanol oxidation reaction.
  • Research articles
    Modeling of specific structure crystallization coupling with dissolution
    Yuanhui JI, Hongliang QIAN, Chang LIU, Xiaohua LU, Xin FENG, Xiaoyan JI,
    2010, 4(1): 52-56. https://doi.org/10.1007/s11705-009-0301-7
    Download PDF
    In this paper, the research framework for specific structure crystallization modeling has been proposed in which four steps are required in order to investigate the rigorous crystallization modeling by thermodynamics. The first is the activity coefficient model of the solution, the second is Solid-Liquid equilibrium, the third and fourth are the dissolution and crystallization kinetics modeling, respectively. Our investigations show that the mechanisms of complex structure formation and microphase transition can be analyzed by combining the dissolution and crystallization kinetics modeling. Moreover, the formation mechanism of the porous KCl has been analyzed, which may provide a reference for the porous structure formation in the advanced material synthesis.
  • Research articles
    Purification and crystallization of xylitol from fermentation broth of corncob hydrolysates
    Jinchao WEI, Qipeng YUAN, Tianxin WANG, Le WANG,
    2010, 4(1): 57-64. https://doi.org/10.1007/s11705-009-0295-1
    Download PDF
    Xylitol, a five-carbon sugar alcohol, is a valuable sugar substitute, and widely used in the pharmaceutical, odontological and food industry due to its interesting properties. In the past decades, the xylitol industry has grown rapidly and more attention has been focused on xylitol purification, which possesses an important proportion of the whole industry. In our paper, the purification and crystallization of xylitol fermentation broth by biotechnology using corncob hydrolysates as substance were studied. An initial xylitol fermentation broth was decolored with activated carbon (1% M-1, 60°C, 165rpm), desalted with a combination of two ion-exchange resins (732 and D301), and residual sugars were separated with UBK-555(Ca2+). Then the solution was vacuum-concentrated up to supersaturation (750g/L xylitol). After adding 1% xylitol crystal seeds, the supersaturated solution was cooled to −20°C for 48h. The crystalline xylitol of a regular tetrahedral shape with purity 95% and crystallization yield 60.2% was obtained from the clarified xylitol fermentation broth. An intact, economical and environmental-friendly route of purification and crystallization of xylitol from fermentation of corncob hydrolysates was obtained, and its experimental procedure and data provided a sound basis for large-scale industrial production.
  • Research articles
    Crystal modification of rifapentine using different solvents
    Kun ZHOU, Jun LI, Jianhong LUO, Dongsheng ZHENG,
    2010, 4(1): 65-69. https://doi.org/10.1007/s11705-009-0302-6
    Download PDF
    Rifapentine crystals with different habits were prepared by recrystallization from selected solvents, such as methanol, ethanol, chloroform, and acetic acid. Scanning electron microscopy, X-ray powder diffractometry, infrared spectrometry, and differential scanning calorimetry were used to investigate the physicochemical characteristics of the prepared crystals. The comparative dissolution behaviors of the newly developed crystals and of rifapentine without being treated were also studied. Results show that the newly developed crystals were different from each other with respect to physical properties but were identical chemically. Needle-shaped crystals were obtained from methanol, ethanol, and chloroform solvents, and the block-shaped crystals were obtained from acetic acid solvent. X-ray diffraction spectra and differential scanning calorimetry investigation on those developed crystals clearly indicate that rifapentine has different crystal structure modification. When the crystal was obtained from acetic acid, the change of crystal habit was originated from the crystal structure modification. The dissolution rate of newly developed crystals was found to be higher than that of rifapentine without being treated. However, the modified crystal obtained from acetic acid shows the lower dissolution rate than crystals obtained from other solvents.
  • Research articles
    Effects of ionic impurities on crystallization of cobalamin
    Baoli SHAO, Hui CHEN, Shuang WANG, Haijun WANG, Shenmin XU,
    2010, 4(1): 70-74. https://doi.org/10.1007/s11705-009-0293-3
    Download PDF
    In this paper, the influence of two typical ionic impurities (Na+ and Mg2+) is investigated with the focused beam reflectance measurement (FBRM) technique. In this system, the on-line FBRM is used as a tool for monitoring the crystallization process of cobalamin by measuring the chord length distribution of particles and the particle counts. It is noted that impurity Mg2+ has a more significant effect than Na2+ in crystal growth of the whole crystallization process. From the microscopic observation of crystals, Mg2+ has an obvious effect on the crystal habit, while Na2+ has little effect. In addition, the crystal habit changes can be monitored by particle vision measurement (PVM). Understanding these effects is helpful to aid optimization and improve process control.
  • Research articles
    Phase equilibrium of the ternary system of NH 4 Cl—CaCl 2 —H 2 O at 50°C
    Xia LI, Junsheng YUAN, Zhiyong JI, Jianxin CHEN,
    2010, 4(1): 75-77. https://doi.org/10.1007/s11705-009-0296-0
    Download PDF
    The equilibrium data on the ternary system of NH4Cl—CaCl2—H2O at 50°C were investigated using the wet-residue method. The experimental results show that there are three pure phase crystal areas of NH4Cl, 2NH4Cl·CaCl2·3H2O and CaCl·2H2O, two mixture phase crystal areas of NH4Cl and 2NH4Cl·CaCl·3H2O, and 2NH4Cl·CaCl2·3H2O and CaCl·2H2O in the system. A new hydration double salt (2NH4Cl·CaCl·3H2O) was found in the ternary equilibrium system for the first time.
  • Research articles
    Influences of additives on the crystal habit of potassium chloride
    Xiaofu GUO, Junsheng YUAN, Zhiyong JI, Min SU,
    2010, 4(1): 78-81. https://doi.org/10.1007/s11705-009-0300-8
    Download PDF
    By means of constant control speed cooling crystallization, the influences of four additives, including lead chloride, cadmium chloride, sodium salicylate, and quaternary ammonium salt, on the crystal habit of KCl were investigated. The results show that the crystal habit of KCl is cube without additives, the crystal habit of KCl is ellipsoid-like in the presence of Pb2+, the crystal habit of KCl is strip in the presence of Cd2+, and the crystal habit of KCl is cavate cube in the presence of sodium salicylate. X-ray diffractometry analysis reveals that these additives can change the crystal habit of KCl but not its crystal structure.
  • Research articles
    Protein microspheres for pulmonary drug delivery
    Yongda SUN,
    2010, 4(1): 82-86. https://doi.org/10.1007/s11705-009-0307-1
    Download PDF
    A new supercritical fluid (SCF) technique was developed for the preparation of microspheres for pulmonary drug delivery (PDD). This technique, based on the anti-solvent process, has incorporated advanced engineering design features to enable improved control of the particle formation process. Human recombinant insulin (HRI) was used as a model compound to evaluate the efficiency of this SCF process. An aqueous solution of HRI with a co-solvent was sprayed into high pressure carbon dioxide that extracted the solvent and water, leading to a dry fine powder with good particle size distribution and near ideal morphology for pulmonary drug delivery.
  • Research articles
    Immobilization of penicillin G acylase onto amino-modified silica hydrogel
    Weibing Dong, Huining HE, Junbo Gong, Victor C. YANG,
    2010, 4(1): 87-90. https://doi.org/10.1007/s11705-009-0298-y
    Download PDF
    Amino-modified silica hydrogel (N-MSHG) was prepared by a simple sol-gel processing via the co-condensation of commercial silica sol with 3-aminopropyltrie-oxysilane. Penicillin G acylase (PGA), a model enzyme, was covalently immobilized onto the N-MSHG and then was used for the enzymatic synthesis of amoxicillin. The samples were characterized by Nitrogen sorption analysis, FT-IR and thermal gravimetric analysis (TGA). The results showed that the amino-modified gel was a mesoporous material with an average pore size of 12.64±0.17nm. The immobilization process was efficient and the immobilized enzyme showed high catalytic efficiency. The yield of the synthesis of amoxicillin in aqueous media was 38% for 2.5h. This sol-gel preparation is simple and shows prominent potential value in industrial processing.
  • Research articles
    A novel cataplasma matrix of traditional Chinese medicine
    Jing TIAN, Xiaolei ZHANG, Xueqin ZHOU,
    2010, 4(1): 91-95. https://doi.org/10.1007/s11705-009-0304-4
    Download PDF
    The aim of this paper was to develop a cataplasma matrix that can be applicable to both watersoluble and liposoluble drugs. The gellan gum and konjaku were employed as the scaffold materials of the matrix. With polyacrylic acid sodium and oligosaccharides as tacktifier, the formula of the cataplasma matrix was optimized in the orthogonal method as: gellan gum 0.4 g, xanthan€gum 0.03 g, konjac glue 0.1 g, glycerin 4 g, Gluco-Adhesive T (GAT) 6 g, Gluco-Adhesive E (GAE) 6 g, polyacrylic acid sodium 0.22 g, and sorbitol 3 g. The 180° peel strength, the tensile strength and the elongation at break was 3.043 N, 0.275 MPa and 91.05%, respectively. Furthermore, the drug-compatibilities of the matrix were investigated with baicalin, berberine and curcumin, which were used as the models of hydrophilic, poor-water-soluble and hydrophobic ingredients. The drug contents could reach 4.12% , 2.42% and 3.75%, while the in vitro release rate were measured as, 361.79, 55.85 and 104.41 μg·cm−2·h−1 for baicalin, berberine and curcumin, respectively. These results indicated that the obtained matrix had good drug-compatibility and drug-release properties for different ingredients.
  • Research articles
    LC-ELSD analysis for simultaneous determination of five components in the Xue-Fu-Zhu-Yu capsules
    Ying GAO, Wenyuan GAO, Xuan DONG, Fengge LI, Xinying YANG,
    2010, 4(1): 96-101. https://doi.org/10.1007/s11705-009-0309-z
    Download PDF
    A reliable and accurate liquid chromatography with evaporative light scattering detection (LC-ELSD) method was developed for simultaneous determination of five constituents in Xue-Fu-Zhu-Yu capsule, a widely used prescription of traditional Chinese medicine (TCM). The chromatographic separation was performed on a Symmetry C18 column (150mm×4.6mm, 5.0μm) using gradient elution of acetonitrile and water (containing 1.0% acetic acid). The flow rate was 0.6mL/min and the temperature of column was 30°C. A good linearity correlation was obtained over the investigated concentration ranges. Recoveries of the five components varied from 97.31% to 99.84% (RSD<4.0%). The validated method was successfully applied to the quality assessment of Xue-Fu-Zhu-Yu capsule.
  • Research articles
    Konjac glucomannan and xanthan gum as compression coat for colonic drug delivery: experimental and theoretical evaluations
    Kang WANG, Jiangyang FAN, Yanjun LIU, Zhimin HE,
    2010, 4(1): 102-108. https://doi.org/10.1007/s11705-009-0299-x
    Download PDF
    Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan (KGM) and xanthan gum (XG) as the compression coat. Diffusion of cimetidine from compression coated tablets was investigated by release experiment in Vitro. 0.22U/mL β-mannanase was applied in the mimic colon solution. The structure of the mixture polysaccharide was studied by an atomic force microscope (AFM). The experimental results indicate that a KGM70 tablet with a 0.4g coat is of good design, due to a less than 5% drug loss in the mimic upper gastrointestinal solution by the synergistic interaction between XG and KGM, and due to about 50% cumulative release in the mimic colon solution by degradation after 24 hours. The release mechanism and model are discussed based on different periods of drug release including the delay of the drug, the constant release without an enzyme and the delay of degradation. Under hydrolysis by β-mannanase, drug release from the tablet with KGM coat shows an exponential increase, while that from the dosage with the mixture polysaccharide coat is an approximately zero-order process in which the constant release rate relates to the release velocity of a non-degraded system, the content of KGM within the coat and the average molecular weight ratio of KGM to XG. It was found that XG was the framework of the polysaccharide mixtures by AFM, which is similar to the analysis results from experiments on drug release.