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Development of pulmonary drug delivery system with dry powder and aqueous suspension aerosols

Research Project

Project/Area Number 08457595
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionGIFU PHARMACEUTICAL UNIVERSITY

Principal Investigator

KAWASHIMA Yoshiaki  Gifu Pharmaceutical University, Pharmacy, Professor, 薬学部, 教授 (30082978)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Hiromitsu  Gifu Pharmaceutical University, Pharmacy, Assistant, 薬学部, 助手 (30275094)
HINO Tomoaki  Gifu Pharmaceutical University, Pharmacy, Assistant (Present, Tokushima Universi, 薬学部, 助教授 (90208778)
TAKEUCHI Hirofumi  Gifu Pharmaceutical University, Pharmacy, Associate Professor, 薬学部, 助教授 (50171616)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1996: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywordsdry powder inhalation / pulmonary delivery / aerosolized aqueous suspension / nanocapsule / lactide / glycolide copolymer / nebulizer / insulin / surface modification / ツインインピンジャー / ペプチド / 表面改質法 / 超音波ネブライザー / ペフチド
Research Abstract

The evaluation methods for the dry powder inhalation dosage forms (DPI) were developed by using cascade impactor and twinimpinger, which have been utilizing to evaluate for metered dose inhalation dosage forms. The in vivo evaluation system for DPI with aerosol generator, dispersing chamber, respirator and particle concentration monitoring system was successfully established. The in vivo evaluation system for the nebulized aqueous suspension was also designed consisting with nebulizer, spacer and respirator.
Dry powder inhalation dosage forms (DPI) with fine dispersibility into the air were successfully developed by modifying particle surface. Pranlukast hydrate (antiasthmatic drug) was used as a model drug particle. Colloidal hydrophilic light anhydrous silicic acid (AEROSIL 200) or hydroxypropylmethylcellulose phthalate (HP-55) nanosphere was used as surface modifying agent. Particle surfaces were modified with AEROSIL 200 and HP-55 by high-speed elliptical-rotor type mixer and freeze … More -dry or spray dry method, respectively. The inhalation characteristics of pranlukast hydrate were improved significantly with the surface modification. The pharmacological activity of surface modified drug after pulmonary administration to guinea pig was also enhanced compared with unmodified particle. The ED5O of pulmonaryly administered drug was smaller than that of intravenous administration.
DL-lactide/glycolide copolymer nanocapsules with insulin were developed by the emulsion solvent diffusion method in water. The nebulized PLGA nanospheres by a sieve type ultrasonic nebulizer were administered by using a respirator into the trachea of the fasted guinea pig. After the administration of insulin encapsulated in the PLGA nanospheres, the blood glucose level reduced significantly and the hypoglycemia prolonged over 48hrs, compared to the nebulized aqueous solution of insulin as a reference (8 hrs). This result could be attributed to the sustained releasing of insulin from the nanospheres deposited widely on the whole lung. It might be possible to develop a new non-parenteral dosage form of peptide drug by using the present system developed. Less

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] 川島 嘉明等: "薬物粒子の表面改質(複合化)によるドライパウダー吸入製剤の設計" 粉体工学会誌. 33. 559-563 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 日野 知証等: "Assessment of inertial separation techniques used for pressurized metered dose inhalers to evaluate respiratory deposition of aerosolized Wogon extract dry powder in vitro" S.T.P.Pharm.Sci.7. 307-314 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Properties of peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods" Europ.J.Pharm.and Biopharm.45. 41-48 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 日野 知証等: "Particle design of Wogon extract dry powder for inhalation aerosols with granulation method" Int.J.Pharm.168. 59-68 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Effect of surface morphorogy of carrier lactose on dry powder for inhalation property pranlukast hydrate" Int.J.Pharm.172. 179-188 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Design of inhalation dry powder of pranlukast hydrate to improve dispersibility by the surface modification with light anhydrous silicic acid (AEROSIL200)" Int.J.Pharm.173. 243-251 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethyl cellulose phtalate nanospheres" Pharm.Res.15. 1748-1752 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Surface-modified antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose" Pharm.Res.15. 1753-1759 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hyperglycemic effect" J.Control Release. 受理. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "造粒プロセスの最新動向と応用技術" 技術情報協会, 27 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "粒子設計工学" 粒体工学会, 20 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Serigano, T.Hino, H.Yamamoto, H.Takeuchi, Y.Kawashima: "The design of inhalation dry powders by the surface modification of drug particles" J.Soc.Powder Technol., Japan. 33. 559-563 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Hino, T.Serigano, H.Yamamoto, H.Takeuchi, T.Niwa and Y Kawashima: "Assessment of inertial separation techniques used for pressurized metered dose inhalers to evaluate respiratory deposition of aerosolized Wogon extract dry powder in vitro" S.T.P.Pharm.Sci.7. 307-314 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, H.Yamamoto, H.Takeuchi, T.Hino and T.Niwa: "Properties of peptide containing DL-lactide/glycolide copolymer nanospheres prepared by novel emulsion solvent diffusion methods" Europ.J.Pharm.and Biopharm.45. 41-48 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Hino, T.Serigano, H.Yamamoto, H.Takeuchi, T.Niwa and Y.Kawashima: "Particle design of Wogon extract dry powder for inhalation aerosols with granulation method" J.Pharm. 168. 59-68 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, T.Serigano, T.Hino, H.Yamamoto and H.Takeuchi: "Effect of surface morphology of carrier lactose on dry powder inhalation property of pranlukast hydrate" Int.J.Pharm.172. 179-188 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, T.Serigano, T.Hino, H.Yamamoto and H.Takeuchi: "Design of inhalation dry powder of pranlukast hydrate to improve dispersibility by the surface modification with light anhydrous silicic acid (AEROSIL 200)" Int.J.Pharm.173. 243-251 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, T.Serigano, T.Hino, H.Yamamoto and H.Takeuchi: "A new powder design method to improve inhalation efficiency of pranlukast hydrate dry powder aerosols by surface modification with hydroxypropylmethylcel-lulose phthalate nanospheres" Pharm.Res.15. 1748-1752 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, T.Serigano, T.Hino, H.Yamamoto and H.Takeuchi: "Surface-modifi*d antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose" Pharm.Res.15. 1753-1759 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kawashima, H.Yamamoto, H.Takeuchi, S.Fujioka and T.Hino: "Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hyperglycemic effect" J.Control.Release. (accepted). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 川島 嘉明等: "Effect of surface morphorogy of carrier lactose on dry powder for inhalation property pranlukast hydrate" Int.J.Pharm.172. 179-188 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "Design of inhalation dry powder of pranlkast hydrate to improve dispersibility by the surface modification with light anhydrous silicic acid(AEROSIL200)" Int.J.Pharm.173. 243-251 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "A new powder design method to improve inhalation efficiency of pranlkast hydrate dry powder aerosols by surface modification with hydroxypropylmethyl cellulose phtalate nanospheres" Pharm.Res.15. 1748-1752 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "Surface-modified antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose" Pharm.Res.15. 1753-1759 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hyperglycemic effect" J.Control Release. (受理). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "造粒プロセスの最新動向と応用技術" 技術情報協会, 27 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 川島 嘉明等: "粒子設計工学" 粉体工学会, 20 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 日野知証 等: "Assessment of Inertial Separation Techniques Used for Presouriged Metered Dese Inhalers to Evaluate Respiratory Depesition" S.T.P.PHARMA SCIENCES. 7. 307-314 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 川島嘉明 等: "Properties of a Peptide Containing DL-lactide/glycolide Copolymer Nanospheres Prepared by Novel Emulsion Soluent Diffusion Methods" European J.Pharm.Biopharm.45. 41-48 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 日野知証 等: "Particle Design of Wogon Extract Dry Powder for Inhalation Aerosobs with Granulation Method" Int J.Pharm.(予定). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 芹ヶ野孝則 等: "薬物粒子の表面改質(複合化)によるドライパウダー吸入製剤の設計" 粉体工学会誌. 33・7. 559-563 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshiaki KAWASHIMA: "International Symposium on Dry Powder Inhalers" Capsugel Library, 8 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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