The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform

Yoshiaki Kawashima - One of the best experts on this subject based on the ideXlab platform.

  • Aerosolization of Lactide/Glycolide Copolymer(PLGA)Nanospheres for Pulmonary Delivery of Peptide-drugs.
    Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Yoshiaki Kawashima
    Abstract:

    : Lactide/glycolide copolymer (PLGA) nanospheres with Nafarelin Acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

  • biodegradable submicron carriers for peptide drugs preparation of dl lactide glycolide copolymer plga nanospheres with Nafarelin Acetate by a novel emulsion phase separation method in an oil system
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • Biodegradable submicron carriers for peptide drugs : Preparation of DL-lactide/glycolide copolymer(PLGA)nanospheres with Nafarelin Acetate by a novel emulsion-phase separation method in an oil system.
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • in vitro drug release behavior of d l lactide glycolide copolymer plga nanospheres with Nafarelin Acetate prepared by a novel spontaneous emulsification solvent diffusion method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

  • In Vitro Drug Release Behavior of D, L‐Lactide/Glycolide Copolymer (PLGA) Nanospheres with Nafarelin Acetate Prepared by a Novel Spontaneous Emulsification Solvent Diffusion Method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

Toshiyuki Niwa - One of the best experts on this subject based on the ideXlab platform.

  • Aerosolization of Lactide/Glycolide Copolymer(PLGA)Nanospheres for Pulmonary Delivery of Peptide-drugs.
    Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Yoshiaki Kawashima
    Abstract:

    : Lactide/glycolide copolymer (PLGA) nanospheres with Nafarelin Acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

  • biodegradable submicron carriers for peptide drugs preparation of dl lactide glycolide copolymer plga nanospheres with Nafarelin Acetate by a novel emulsion phase separation method in an oil system
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • Biodegradable submicron carriers for peptide drugs : Preparation of DL-lactide/glycolide copolymer(PLGA)nanospheres with Nafarelin Acetate by a novel emulsion-phase separation method in an oil system.
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • in vitro drug release behavior of d l lactide glycolide copolymer plga nanospheres with Nafarelin Acetate prepared by a novel spontaneous emulsification solvent diffusion method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

  • In Vitro Drug Release Behavior of D, L‐Lactide/Glycolide Copolymer (PLGA) Nanospheres with Nafarelin Acetate Prepared by a Novel Spontaneous Emulsification Solvent Diffusion Method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

Hirofumi Takeuchi - One of the best experts on this subject based on the ideXlab platform.

  • Aerosolization of Lactide/Glycolide Copolymer(PLGA)Nanospheres for Pulmonary Delivery of Peptide-drugs.
    Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Yoshiaki Kawashima
    Abstract:

    : Lactide/glycolide copolymer (PLGA) nanospheres with Nafarelin Acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

  • biodegradable submicron carriers for peptide drugs preparation of dl lactide glycolide copolymer plga nanospheres with Nafarelin Acetate by a novel emulsion phase separation method in an oil system
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • Biodegradable submicron carriers for peptide drugs : Preparation of DL-lactide/glycolide copolymer(PLGA)nanospheres with Nafarelin Acetate by a novel emulsion-phase separation method in an oil system.
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • in vitro drug release behavior of d l lactide glycolide copolymer plga nanospheres with Nafarelin Acetate prepared by a novel spontaneous emulsification solvent diffusion method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

  • In Vitro Drug Release Behavior of D, L‐Lactide/Glycolide Copolymer (PLGA) Nanospheres with Nafarelin Acetate Prepared by a Novel Spontaneous Emulsification Solvent Diffusion Method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

Tomoaki Hino - One of the best experts on this subject based on the ideXlab platform.

  • Aerosolization of Lactide/Glycolide Copolymer(PLGA)Nanospheres for Pulmonary Delivery of Peptide-drugs.
    Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Yoshiaki Kawashima
    Abstract:

    : Lactide/glycolide copolymer (PLGA) nanospheres with Nafarelin Acetate (NA) used as a model peptide-drug have been developed by the emulsion-phase separation method in an oil phase as reported previously. In the present study, the aerosolization of nanospheres in dry and wet dispersion methods was investigated in vitro to evaluate their applications to pulmonary delivery of peptide-drug. The size distribution of aerosolized nanosphere dispersions and pulmonary deposition behaviors of inhaled particles were investigated using a lazer diffraction light-scattering particle sizer and an artificial model lung (Cascade Impactor: CI), respectively. It was found that the freeze-drying of nanospheres with a hydrophilic surface active agent effectively improved the inhalation behavior. Further, the mixing of nanospheres with lactose led to the reduction of their adhesion to an inhalation device (Spinhaler). It was supposed that the mists of nanosphere-suspension generated from a jet nebulizer might be inhaled into the lower bronchus and alveolus, because their respirable fraction (RF) value, i.e., the deposition percentage on stage 2 to 6 of CI, defined as a pulmonary inhalation index, reached a maximum of over 50%.

  • biodegradable submicron carriers for peptide drugs preparation of dl lactide glycolide copolymer plga nanospheres with Nafarelin Acetate by a novel emulsion phase separation method in an oil system
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • Biodegradable submicron carriers for peptide drugs : Preparation of DL-lactide/glycolide copolymer(PLGA)nanospheres with Nafarelin Acetate by a novel emulsion-phase separation method in an oil system.
    International Journal of Pharmaceutics, 1995
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Masami Nohara, Yoshiaki Kawashima
    Abstract:

    Abstract PLGA nanospheres, biodegradable polymeric carriers for peptide drugs, were prepared by a novel emulsion-phase separation method. The preparation was carried out in an oil phase system in order to improve the entrapment efficiency of water-soluble peptide. An LH-RH analogue (Nafarelin Acetate (NA)) was employed as a model peptide drug to investigate the encapsulation efficiency. An aqueous solution of the drug was emulsified by addition with stirring to a dichloromethane-acetone mixture containing dissolved PLGA. The gradual addition of Triester oil (caprylate and caprate triglyceride) into the resultant w/o emulsion induced phase separation of PLGA at the interface of aqueous droplets. It was found that the aqueous droplets effectively worked as a coacervation-inducing agent of the polymer. PLGA coacervates precipitated around the aqueous emulsion droplets containing the peptide which were hardened by evaporation of the solvent, producing spherical drug carriers. The presence of surfactant significantly reduced the size of the aqueous droplets, resulting in submicron-sized PLGA spheres (mean diameter, 500–800 nm). The recovery of drug entrapped in the nanospheres was markedly increased compared with our previous preparation technique in a water system. Further, optimum conditions in the present method for preparing nanospheres were established to enhance the recovery of nanospheres and the efficiency of drug entrapment.

  • in vitro drug release behavior of d l lactide glycolide copolymer plga nanospheres with Nafarelin Acetate prepared by a novel spontaneous emulsification solvent diffusion method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

  • In Vitro Drug Release Behavior of D, L‐Lactide/Glycolide Copolymer (PLGA) Nanospheres with Nafarelin Acetate Prepared by a Novel Spontaneous Emulsification Solvent Diffusion Method
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: Toshiyuki Niwa, Hirofumi Takeuchi, Tomoaki Hino, Noriyuki Kunou, Yoshiaki Kawashima
    Abstract:

    Abstract Nanospheres with D, L‐lactide/glycolide copolymer (PLGA) were prepared as a biodegradable and biocompatible polymeric carrier for peptide drugs by a novel spontaneous emulsification solvent diffusion mathod. Nafarelin Acetate (NA), a luteinizing hormone‐releasing hormone analogue, was employed as a model peptide drug to investigate the encapsulation efficiency. The drug and PLGA, dissolved in an acetone–dichloromethane–water mixture, were poured into an aqueous solution of polyvinyl alcohol under moderate stirring at room temperature. Spontaneous emulsification arising from a rapid diffusion of acetone from the organic to the aqueous phase enables preparation of PLGA submicron spheres 200–300 nm in size. The entrapment of NA in nanospheres was improved by blending low molecular weight (Mw = 4500) PLGA with higher molecular weight PLGA due to the synergistic effect of thrapid deposition of PLGA and the ionic interaction between NA and PLGA. By coadmixing a small amount of negatively charged phospholipids such as dipalmitoyl phosphatidylglycerol or dicetyl phosphate, the leakage of water‐soluble NA was further prevented. The NA encapsulated in PLGA nanospheres was more stable than native NA in acidic medium (pH = 1.2). The drug‐release behavior from nanospheres suspended in the disintegration test solution no. 1 (Japanese Pharmacopeia XII) exhibited a biphasic pattern. It was found that the initial burst of release might be due to the degradation of the PLGA chain, as monitored by gel permeation chromatography. At a later stage, the drug was released more slowly, the rate of which was determined by the diffusion of the drug in the poruos matrix structure. In the test solution no. 2(pH = 6.8), the drug release rate from the nanospheres was much slower than that in solution no. 1.

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  • comparison between Nafarelin and leuprolide Acetate for in vitro fertilization preliminary clinical study
    Fertility and Sterility, 1994
    Co-Authors: Zoetania Nery Dantas, Mario Vicino, Jose P Balmaceda, Ricardo H Asch, Sergio C Stone
    Abstract:

    Objective To evaluate the clinical effect of two different biochemical GnRH agonists (GnRH-a), Nafarelin Acetate and leuprolide Acetate (LA), as adjunct to induction of ovulation in patients for IVF. Design Twenty-four women were assigned randomly to either Nafarelin Acetate or LA during IVF cycles. Setting University-affiliated clinics. Patients Infertile women undergoing IVF cycles in an academic research environment. Interventions Intranasal Nafarelin at a dosage of 200 μ g twice daily or LA at a dose of 1mg/d SC was administered. Blood samples were collected on day 21 of previous cycle, days 2 and 8, and before hCG injection. Main Outcome Measure Patient response as indicated by follicular phase serum levels of E 2 , FSH, and LH. Results Hormone profiles on cycle day 2 showed no statistical difference between both GnRH-a groups in FSH levels and a slight statistical difference for E 2 levels. Patient response as demonstrated by follicular phase of E 2 , FSH, and LH measured on cycle day 8 and the day of hCG injection showed no statistically significant difference in both groups. Furthermore, the mean number of follicles, eggs retrieved, egg quality, fertilization rate, and number of embryos transferred and frozen were similar. The cycle cancellation rate and pregnancy rate per stimulation start were also not statistically different between the two groups. Conclusion The study shows the comparable efficacy of these two drugs in controlled ovarian hyperstimulation (COH) protocols. The easy administration of Nafarelin with prompt nasal absorption and the readily achieved blood level made Nafarelin an option for use in COH in assisted reproductive technology.

  • Comparison between Nafarelin and leuprolide Acetate for in vitro fertilization: preliminary clinical study * †
    Fertility and Sterility, 1994
    Co-Authors: Zoetania Nery Dantas, Mario Vicino, Jose P Balmaceda, Ricardo H Asch, Sergio C Stone
    Abstract:

    Objective To evaluate the clinical effect of two different biochemical GnRH agonists (GnRH-a), Nafarelin Acetate and leuprolide Acetate (LA), as adjunct to induction of ovulation in patients for IVF. Design Twenty-four women were assigned randomly to either Nafarelin Acetate or LA during IVF cycles. Setting University-affiliated clinics. Patients Infertile women undergoing IVF cycles in an academic research environment. Interventions Intranasal Nafarelin at a dosage of 200 μ g twice daily or LA at a dose of 1mg/d SC was administered. Blood samples were collected on day 21 of previous cycle, days 2 and 8, and before hCG injection. Main Outcome Measure Patient response as indicated by follicular phase serum levels of E 2 , FSH, and LH. Results Hormone profiles on cycle day 2 showed no statistical difference between both GnRH-a groups in FSH levels and a slight statistical difference for E 2 levels. Patient response as demonstrated by follicular phase of E 2 , FSH, and LH measured on cycle day 8 and the day of hCG injection showed no statistically significant difference in both groups. Furthermore, the mean number of follicles, eggs retrieved, egg quality, fertilization rate, and number of embryos transferred and frozen were similar. The cycle cancellation rate and pregnancy rate per stimulation start were also not statistically different between the two groups. Conclusion The study shows the comparable efficacy of these two drugs in controlled ovarian hyperstimulation (COH) protocols. The easy administration of Nafarelin with prompt nasal absorption and the readily achieved blood level made Nafarelin an option for use in COH in assisted reproductive technology.