The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Yoshiaki Kawashima - One of the best experts on this subject based on the ideXlab platform.
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Effect of three types of additives in poor solvent on preparation of sustained-release nitrendipine microspheres by the quasi-emulsion solvent diffusion method
Journal of Drug Delivery Science and Technology, 2005Co-Authors: Mingshi Yang, Fude Cui, Yong Fan, B. You, K. Ren, H. Feng, Yoshiaki KawashimaAbstract:Sustained-release microspheres of nitrendipine with Hydroxypropylmethylcellulose Phthalate (HP-55) having a solid dispersion structure were prepared by using the quasi-emulsion solvent diffusion method of the spherical crystallization technique. To investigate the effect of the additives in poor solvent on the preparation of the nitrendipine microspheres, three types of additives, i.e. C 12 H 25 ,NaO 4 S (sodium dodecyl sulfate), NaOH, and KH 2 PO 4 NaOH mixture, were chosen. The resultant microspheres were evaluated with respect to their recoveries, micromeritic properties and release rates. The mechanisms involved in the effect of different poor solvents on formation of the microspheres are discussed. The sustained-release nitrendipine microspheres could not be prepared without using any additives added to the poor solvent. The additives dissolved in poor solvent could affect the micromeritic properties and the release profiles of the resultant microspheres. On increasing the amount of additives, the total recoveries of microspheres were increased and the average diameter of the microspheres was reduced. It was found that a dissociation of HP-55 in poor solvent contributed to the formation of sustained-release nitrendipine microspheres. The release rate of the microspheres prepared with sodium dodecyl sulfate aqueous solution was slower than that of the other two additives, due to the more dense structure formed. Since HP-55, a pH-dependent polymer, was formulated in the present microspheres, the pH value of dissolution medium was one of critical factors to determine the dissolution rate.
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A novel pH-dependent gradient-release delivery system for nitrendipine: I. Manufacturing, evaluation in vitro and bioavailability in healthy dogs
Journal of controlled release : official journal of the Controlled Release Society, 2004Co-Authors: Mingshi Yang, Fude Cui, Bengang You, Jian You, Liang Wang, Liqiang Zhang, Yoshiaki KawashimaAbstract:Abstract A novel pH-dependent gradient-release delivery system was developed by mixing three kinds of pH-dependent microspheres. Nitrendipine, a dihydropyridine calcium antagonist, was selected as the poorly water-soluble model drug. To obtain gradient-release of the active drug in the stomach, duodenum and lower segment of the small intestine, respectively, three kinds of pH-dependent polymers, i.e. Acrylic resins Eudragit E-100, Hydroxypropylmethylcellulose Phthalate and Hydroxypropylmethylcellulose acetate succinate, were formulated to produce the microspheres, which dissolve at an acid condition, the pH of ≥5.5 and ≥6.5, respectively. The quasi-emulsion solvent diffusion method was employed in the manufacturing process for the microspheres. All three kinds of microspheres had a highly spherical shape and high incorporation efficiency (>91.0%). The particle sizes were mainly affected by the agitation speed and temperature of the manufacturing process. The results of X-ray diffraction suggested that nitrendipine in the microspheres was molecularly dispersed in an amorphous state. The drug dissolution behavior of the system under the simulated gastrointestinal pH conditions revealed obvious gradient-release characteristics. The dissolution profiles and content of the systems stored at a temperature of 40 °C and a relative humidity of 75% were unchanged during a 3-month period of accelerating storage conditions. The results of the bioavailability testing in six healthy dogs suggested that the pH-dependent gradient-release delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the T max value in vivo.
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The preparation of enteric solid dispersions with Hydroxypropylmethylcellulose acetate succinate using a twin-screw extruder
Journal of Drug Delivery Science and Technology, 2004Co-Authors: K. Nakamichi, T. Nakano, S. Izumi, H. Yasuura, Yoshiaki KawashimaAbstract:Hydroxypropylmethylcellulose acetate succinate (HPMCAS) has a ductile nature at ca. 130°C and can be readily extruded with a twin-screw extruder. It was found that dissolved HPMCAS retarded the crystallization of nifedipine (NP) in an aqueous medium compared with Hydroxypropylmethylcellulose Phthalate (HPMCP) and was a suitable carrier for preparing NP solid dispersions. Three weight ratios of the mixtures of NP and HPMCAS (1:1, 1:3, 1:5) were extruded with a twin-screw extruder. At a weight ratio of 1:5, crystalline peaks of NP observed in the physical mixture were not detected by powder X-ray diffractometry and differential scanning calorimetry (DSC). In an alkali medium, the concentration of dissolved NP increased and was maintained. Similarly, indomethacin (IM), nicardipine hydrochloride and oxybutynin hydrochloride with HPMCAS (weight ratio 1:5) were extruded. There were no crystalline peaks of each drug in the powder X-ray diffractometry and DSC scans. Also, the dissolution of IM was improved by extrusion. These results show that HPMCAS can be used to improve the dissolution of poorly water-soluble compounds and a twin-screw extruder is useful for efficiently preparing a solid dispersion.
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The role of the kneading paddle and the effects of screw revolution speed and water content on the preparation of solid dispersions using a twin-screw extruder.
International journal of pharmaceutics, 2002Co-Authors: Kouichi Nakamichi, Tomio Nakano, Hiroyuki Yasuura, Shogo Izumi, Yoshiaki KawashimaAbstract:The twin-screw hot-melt extrusion process is useful for preparing solid dispersions which can improve the dissolution and absorption of drugs. The kneading paddle elements of the screws play an important role in changing the crystallinity and dissolution properties of a solid dispersion of kneaded nifedipine-Hydroxypropylmethylcellulose Phthalate (NP-HPMCP). After operating the machine, a small amount of kneaded material adhering to the screws was collected and its physicochemical properties examined. Samples from the kneading paddle with a twist angle of 60 degrees were transparent and exhibited super-saturation on dissolution testing. When the kneading paddle elements were detached from the screws and only the feed screw elements were operated, the physicochemical properties of the extruded material were significantly influenced by the operating conditions of the machine e.g. revolution rate of screws, and the amount of water added to the feed materials. Slow revolution of the screws and the addition of a suitable amount of water to the mixture increased the rate of drug dissolution, although no super-saturation occurred. As the kneading paddle elements can retain the mixture in the machine for a longer period under intense shear, desired solid dispersions can be prepared routinely irrespective of the operating conditions. Moreover, a capillary rheometer can be useful to predetermine the amount of water added and the temperature for the preparation of solid dispersions using a twin-screw extruder.
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Design of Polymeric Nanoparticulate System for Mucosal Peptide Delivery.
Drug Delivery System, 2000Co-Authors: Hiromitsu Yamamoto, Hirofumi Takeuchi, Yoshiaki KawashimaAbstract:Firstly the superior properties of polymeric nanoparticulate systems to other systems for mucosal peptide delivery as an alternative injection are over looked. Then novel mucosal peptide delivery systems developed by using those particulate systems are reviewed with introducing our systems. The oral mucoadhesive lactide glycolide copolymer (PLGA) nanospheres improved the absorption of calcitonin due to prolonging the retention time and the drug release at the absorption site in rat. Powdered pulmonary systems with PLGA nanospheres and Hydroxypropylmethylcellulose Phthalate (HPMCP) nanospheres for prolonged and rapid acting peptide delivery systems were successfully developed by us, respectively.
Hirofumi Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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Design of Polymeric Nanoparticulate System for Mucosal Peptide Delivery.
Drug Delivery System, 2000Co-Authors: Hiromitsu Yamamoto, Hirofumi Takeuchi, Yoshiaki KawashimaAbstract:Firstly the superior properties of polymeric nanoparticulate systems to other systems for mucosal peptide delivery as an alternative injection are over looked. Then novel mucosal peptide delivery systems developed by using those particulate systems are reviewed with introducing our systems. The oral mucoadhesive lactide glycolide copolymer (PLGA) nanospheres improved the absorption of calcitonin due to prolonging the retention time and the drug release at the absorption site in rat. Powdered pulmonary systems with PLGA nanospheres and Hydroxypropylmethylcellulose Phthalate (HPMCP) nanospheres for prolonged and rapid acting peptide delivery systems were successfully developed by us, respectively.
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A New Powder Design Method to Improve Inhalation Efficiency of Pranlukast Hydrate Dry Powder Aerosols by Surface Modification with Hydroxypropylmethylcellulose Phthalate Nanospheres
Pharmaceutical Research, 1998Co-Authors: Yoshiaki Kawashima, Takanori Serigano, Tomoaki Hino, Hiromitsu Yamamoto, Hirofumi TakeuchiAbstract:Purpose . A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, Hydroxypropylmethylcellulose Phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro. Methods . Drug particles were introduced to aqueous colloidal HPMCP dispersions prepared by emulsion-solvent diffusion techniques followed by freeze- or spray-drying of the resultant aqueous dispersions. The surface-modified powders obtained with HPMCP nanospheres and their mixture with lactose powders were aerosolized by Spinhaler and their mode of deposition in lung was evaluated in vitro using a twin impinger. To elucidate the inhalation mechanism of these surface modified particles, we measured their modified micromeritic properties, such as surface topography, specific surface area, dissolution rate, and dispersibility in air. Results . Dramatically improved inhalation properties of the surface modified powder, i.e. a two-fold increase in emission and a three-fold increase in delivery to deep lung, were found in vitro compared with the original unmodified powder. Improved inhalation was also found with the surf ace-modified drug deposited on lactose particles. Those improvements were attributed to the increased surface roughness and hydrophilicity of the surface-modified particles, and the resultant increased dispersibility in air. Conclusions . Surface modification of hydrophobic drug particles with HPMCP nanospheres to improve hydrophilicity was extremely useful in increasing the inhalation efficiency of the drug itself and the drug deposited on carrier; this was attributed to increased dispersibility in air and emission from the device, for spray- and freeze-dried particles, respectively.
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the development of an aqueous polymeric enteric coating system with Hydroxypropylmethylcellulose Phthalate nanoparticles
Journal of The Society of Powder Technology Japan, 1998Co-Authors: Hiromitsu Yamamoto, Hirofumi Takeuchi, Ikumasa Ohno, Yoshiaki KawashimaAbstract:A new aqueous polymeric enteric coating system was developed with the aqueous dispersions of Hydroxypropylmethylcellulose Phthalate (HPMCP) nanoparticles prepared by the emulsion solvent diffusion method. The average diameter of HPMCP nanoparticles (pseudolatex) was 120nm with a polydispersity index of 0.172. The enteric coating of riboflavin granules with the present system was successfully conducted using a fluidized bed coating.To obtain satisfactory acid resistance (i. e. enteric properties) of the coated granules with HPMCP nanoparticles, the coating film thickness needed to be 10μm or more. The coating amount required to obtain satisfactory acid resistance of the coated granules with HPMCP nanoparticles was found to be much smaller than with the pulverized HPMCP available on the market. This is because the coating film with HPMCP nanoparticles was closer and more uniform than that with pulverized HPMCP particles. The equation to predict the amount of polymer required for satisfactory enteric coating was proposed in the present study.
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A New Powder Design Method to Improve Inhalation Efficiency of Pranlukast Hydrate Dry Powder Aerosols by Surface Modification with Hydroxypropylmethylcellulose Phthalate Nanospheres.
Pharmaceutical research, 1998Co-Authors: Yoshiaki Kawashima, Takanori Serigano, Tomoaki Hino, Hiromitsu Yamamoto, Hirofumi TakeuchiAbstract:Purpose. A new particle design method to improve the aerosolization properties of a dry powder inhalation system was developed using surface modification of hydrophobic drug powders (pranlukast hydrate) with ultrafine hydrophilic particles, Hydroxypropylmethylcellulose Phthalate (HPMCP) nanospheres. The mechanism of the improved inhalation properties of the surface-modified particles and their deposits on carrier particles (lactose) was clarified in vitro.
Sante Martelli - One of the best experts on this subject based on the ideXlab platform.
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Polymers with pH-dependent solubility: possibility of use in the formulation of gastroresistant and controlled-release matrix tablets.
Drug development and industrial pharmacy, 2000Co-Authors: Giovanni Filippo Palmieri, S. Michelini, P. Di Martino, Sante MartelliAbstract:Polymers usually utilized for gastroresistant film coating of tablets or pellets such as cellulose acetate Phthalate (CAP), cellulose acetate trimellitate (CAT), Hydroxypropylmethylcellulose Phthalate (HPMCP), and Eudragit L and S were used in the preparation of drug/polymer matrix tablets. These tablets were prepared either by direct compression of both powders or by the formulation of microspheres that were then compressed. The microspheres were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry analyses. Dissolution studies were finally carried out to verify if the tablets possessed gastroresistant or controlled-release characteristics. Except for Eudragit L, the polymers can be used under certain conditions in the formulation of modified-release tablets.
Lynne S. Taylor - One of the best experts on this subject based on the ideXlab platform.
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Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation.
Journal of pharmaceutical sciences, 2020Co-Authors: Sonal Bhujbal, Lynne S. Taylor, Vaibhav Pathak, Dmitry Zemlyanov, Qi Tony ZhouAbstract:This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, Hydroxypropylmethylcellulose Phthalate (HPMCP), Hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid-ethyl acrylate) (EL100) and cellulose acetate Phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40°C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 hours, which is significantly higher than the currently marketed formulation of Coartem® (
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Leaching of Lopinavir Amorphous Solid Dispersions in Acidic Media
Pharmaceutical Research, 2016Co-Authors: James D. Ormes, Lynne S. TaylorAbstract:Purpose Amorphous solid dispersions (ASDs) formulated with acid-insoluble (enteric) polymers form suspensions in acidic media where the polymer is largely insoluble. However, a small amount of drug can dissolve and a supersaturated solution may be generated. The goal of this study was to gain insight into the leaching mechanisms of both drug and polymer from the suspended particles, studying the impact of solution additives such as surfactants. Methods ASDs were prepared by spray drying lopinavir (LPV) with an enteric polymer, either Hydroxypropylmethylcellulose acetate succinate (HPMCAS) or Hydroxypropylmethylcellulose Phthalate (HPMCP). Four surfactants and a suspending agent were added to the liquid media to evaluate the effect of these excipients on leaching. pH 3 and pH 5 buffers were used to investigate the effect of pH. Results The extent of drug leaching from the amorphous formulation was proportional to the crystalline solubility of the drug in the same medium. All surfactants promoted solubilization of LPV with the exception of poloxamer and sodium dodecyl sulfate-HPMCP combinations. A small amount of polymer ionization significantly enhanced LPV leaching in solutions containing an ionic surfactant. Conclusions The mechanism of enhanced leaching appeared to be solubilization, with the apparent supersaturation remaining the same for systems containing the same polymer.
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Leaching of Lopinavir Amorphous Solid Dispersions in Acidic Media
Pharmaceutical research, 2016Co-Authors: James D. Ormes, Lynne S. TaylorAbstract:Amorphous solid dispersions (ASDs) formulated with acid-insoluble (enteric) polymers form suspensions in acidic media where the polymer is largely insoluble. However, a small amount of drug can dissolve and a supersaturated solution may be generated. The goal of this study was to gain insight into the leaching mechanisms of both drug and polymer from the suspended particles, studying the impact of solution additives such as surfactants. ASDs were prepared by spray drying lopinavir (LPV) with an enteric polymer, either Hydroxypropylmethylcellulose acetate succinate (HPMCAS) or Hydroxypropylmethylcellulose Phthalate (HPMCP). Four surfactants and a suspending agent were added to the liquid media to evaluate the effect of these excipients on leaching. pH 3 and pH 5 buffers were used to investigate the effect of pH. The extent of drug leaching from the amorphous formulation was proportional to the crystalline solubility of the drug in the same medium. All surfactants promoted solubilization of LPV with the exception of poloxamer and sodium dodecyl sulfate-HPMCP combinations. A small amount of polymer ionization significantly enhanced LPV leaching in solutions containing an ionic surfactant. The mechanism of enhanced leaching appeared to be solubilization, with the apparent supersaturation remaining the same for systems containing the same polymer.
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Chiral discrimination by a cellulose polymer: differential crystallization inhibition of enantiomers in amorphous dispersions
CrystEngComm, 2015Co-Authors: Takafumi Sato, Lynne S. TaylorAbstract:With the goal of better understanding how polymers inhibit crystallization in amorphous solid dispersions, crystal growth rates of the R and S enantiomers of a model chiral compound in the presence of chiral and achiral polymers were evaluated. The crystal growth rates of enantiomers in undercooled melts were inhibited to different extents by the same mass fraction of a chiral polymer, hydroxypropylmethyl cellulose acetate succinate. This is most likely due to differences in the ability of each enantiomer to form hydrogen bonding interactions with the polymer, which in turn impacts the crystallization behavior of the low molecular weight organic compound. In contrast, the achiral polymer polyvinylpyrrolidone, and the chiral polymer, Hydroxypropylmethylcellulose Phthalate showed the same inhibitory impact on each enantiomer.
Katsumi Miyazaki - One of the best experts on this subject based on the ideXlab platform.
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improving the oral bioavailability of albendazole in rabbits by the solid dispersion technique
Journal of Pharmacy and Pharmacology, 1999Co-Authors: Naonori Kohri, Yasuko Yamayoshi, He Xin, Ken Iseki, Naoki Sato, Satoru Todo, Katsumi MiyazakiAbstract:We have investigated the oral bioavailability of granules of albendazole, a drug used for treating echinococcosis in man, prepared by the solid dispersion technique. Rapid dissolution and supersaturation were observed when Hydroxypropylmethylcellulose and Hydroxypropylmethylcellulose Phthalate were used as carriers in the solid dispersion. They inhibited the crystallization of albendazole from the supersaturated solution and maintained an amorphous state for 8h. Gastric acidity-controlled rabbits were used to evaluate the variation in absorption after oral administration of the albendazole solid dispersion. For rabbits with low gastric acidity the bioavailability of orally administered albendazole in the granular form prepared by solid dispersion was more than three times that of albendazole in physical mixtures. These results suggest that the bioavailability of albendazole in solid dispersions might be high even if there is a great variation in the gastric pH of patients.
