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2002 Fiscal Year Final Research Report Summary

Optimization of transdermal and transmucosal drug delivery systems utilizing artificial neural networks

Research Project

Project/Area Number 12672096
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Physical pharmacy
Research InstitutionHoshi University

Principal Investigator

TAKAYAMA Kozo  Hoshi University, Pharmaceutics, Professor, 薬学部, 教授 (00130758)

Project Period (FY) 2000 – 2002
KeywordsOptimization / Artificial neural network / Response surface method / Formulation / Transdermal absorption / Chemical enhancer / Drug delivery / Ketoprofen
Research Abstract

A pharmaceutical formulation is composed of several formulation factors and process variables. Several responses relating to the effectiveness, usefulness, stability, as well as safety must be optimized simultaneously. Consequently, expertise and experience are required to design acceptable pharmaceutical formulations. A response surface method (RSM) has widely been used for selecting acceptable pharmaceutical formulations. However, prediction of pharmaceutical responses based on the second-order polynomial equation commonly used in RSM, is often limited to low levels, resulting in poor estimations of optimal formulations. A multi-objective simultaneous optimization method incorporating an artificial neural network (ANN) was developed. The method was applied to the optimization of ketoprofen hydrogel formulations including 1-O-ethyl-3-n-butylcyclohexanol as absorption enhancer. ANNs are being increasingly used in pharmaceutical research to predict the nonlinear relationship between causal factors and response variables. The observed results of several characteristics in the optimum formulations coincided well with the predictions, suggesting superior function of the ANN approach.

  • Research Products

    (72 results)

All Other

All Publications (72 results)

  • [Publications] S.H.Hwang: "High entrapment of insulin and bovine serum albumin into neutral and positively-charged liposomes by the remote loading method"Chem.Pharm.Bull.. 48. 325-329 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Onuki: "In vivo effects of highly purified docosahexaenoic acid on rectal insulin absorption"Int.J.Pharm.. 198. 147-156 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Obata: "Effect of synthesized cyclohexanol derivatives using L-menthol as a lead compound on the percutaneous absorption of ketoprofen"Int.J.Pharm.. 198. 191-200 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Maitani: "The enhancing effect of soybean-derived sterylglucoside and β-sitosterol β-D-glucoside on nasal absorption in rabbits"Int.J.Pharm.. 2000. 17-26 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 浅井和範: "薬物血中濃度分析における固相抽出法を用いたセミミクロ高速液体クロマトグラフィーの有用性"病院薬学. 26. 219-226 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Obata: "Evaluation of skin damage caused by percutaneous absorption enhancers using fractal analysis"J.Pharm.Sci.. 89. 556-561 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小幡誉子: "ジルチアゼムの皮膚透過に及ぼすメントールおよびO-エチルメントールの効果"DDS. 15. 129-136 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Muramatsu: "Electron spin resonance studies of dipalmitoylphosphatidylcholine liposomes containing soybean-derived sterylglucoside"Chem.Pharm.Bull.. 48. 610-613 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Takayama: "Formula optimization of theophylline tablet based on artificial neural networks"J.Controlled Rel.. 68. 145-186 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.P.Wang: "In vivo evaluation of doxorubicin carried with long circulating and remote loading proliposome"Int. J. Pharm.. 203. 61-69 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Kajita: "Enhanced enteral bioavailability of vancomycin using water-in-oil-in-water multiple emulsion incorporating highly purified unsaturated fatty acid"J.Pharm.Sci.. 89. 1243-1252 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Maitani: "Physicochemical characteristics and transfection efficiency of DNA in liposomes with soybean-derived sterylglucoside into HepG2 cells"J.Pharm.Sci.Technol., Jpn.. 61. 1-10 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Morishita: "Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin"Int.J.Pharm.. 212. 289-293 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩田政則: "徐放性プロカイン坐薬の物性と薬物吸収に対するカプリン酸ナトリウムの添加効果"医療薬学. 27. 137-142 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Obata: "Evaluation and structure-activity relationship of synthesized cyclohexanol derivatives on percutaneous absorption of ketoprofen"Int.J.Pharm.. 212. 223-231 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.P.Wang: "Pharmacokinetics and antitumor effect of doxorubicin carried by stealth and remote loading proliposome"Pharm.Res.. 17. 782-787 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮崎靖則: "反対荷電を持つデキストラン誘導体間の複合体形成に関する検討"薬剤学. 61. 59-70 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Maitani: "Modified ethanol injection method for liposomes containing β-sitosterol β-D-glucoside"J.Liposome Research. 11. 115-125 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Maitani: "Efficency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrier in HepG2 cells"J.Controlled Rel.. 75. 137-142 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C.J.Li: "Promoting mechanism of menthol derivatives, 1-O-ethyl-3-buthylcylohexanol, on the percutaneous absorption of ketoprofen"Biol.Pharm.Bull.. 24. 1044-1048 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] P.C.Wu: "Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer"J.Pharm.Sci.. 90. 1004-1014 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.H.Hwang: "Liver-targeted gene transfer into a human hepattoblastoma cell line and in vivo by steryglucoside-containg cationic liposomes"Gene Therapy. 8. 1276-1280 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Watanabe: "Utility of the three-dimensional cultured human skin model as a tool to evaluate skin permeation of drugs"Altern.Animal Test.Experiment.. 8. 1-14 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 安野伸浩: "Ethenzamideの経皮吸収に及ぼすN-Methyl-2-pyrrolidoneの効果"薬剤学. 61. 154-162 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakamura: "Enhancement of FITC-dextran absorption via nasal mucosa by nanoparticles based on β-sitosterol β-D-glucoside and its aglycon"S.T.P.Pharm., Sci.. 12. 63-68 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 宮崎靖則: "固体状態におけるデキストラン誘導体の粘膜付着性の評価"薬剤学. 62. 14-22 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakamura: "The enhancing effect of nasal absorption of FITC-dextran 4,400 by β-sitosterol β-D-glicoside in rabbits"J.Controlled Rel.. 79. 147-155 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.P.Wang: "Antitumor effects and pharmacokinetics of aclacinomycin A carried by injectable emulsions composed of vitamin E, cholesterol and PEG-lipid"J.Pharm.Sci.. 91. 1128-1134 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kawano: "Liver targeting liposomes containing β-sitosterol glucoside with regard to penetration-enhancing effect on HepG2 cells"Biol.Pharm.Bull.. 25. 766-770 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Kanebako: "Transdermal delivery of indomethacin by iontophoresis"Biol.Pharm.Bull.. 25. 779-782 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Sudo: "Elevation of plasma levels of L-dopa in transdermal administration of L-dopa-butylester in rats"Drug Dev.Ind.Pharm.. 28. 59-65 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Morishita: "Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers"J.Controlled Rel.. 81. 25-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Tsutsumi: "Buccal absorption of ergotamine tertrate using the bioadhesive tablet system in guinea-pigs"Int.J.Pharm.. 238. 161-170 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Morita: "Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera"Chem.Pharm.Bull.. 50. 1181-1186 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Asai: "The effects of water-soluble cyclodextrine on the histological integrity of the rat nasal mucosa"Int.J.Pharm.. 246. 25-35 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Kanebako: "Evaluation of skin barrier function using direct current I : Effect of conductivity, voltage, distance between electrodes and electrode area"Biol.Pharm.Bull.. 25. 1456-1460 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 小川法子: "花粉症治療を目的としたflunisolide含有持続性鼻腔用軟膏の開発"薬剤学. 63. 161-168 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Kanebako: "Evaluation of skin barrier function using direct current II : Effects of duty cycle, waveform, frequency and mode"Biol.Pharm.Bull.. 25. 1623-1628 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakamura: "Regional intestinal absorption of FITC-dextran 4,400 with nanoparticles based on β-sitosterol β-D-glucoside in rats"J.Pharm.Sci.. 92. 311-318 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Takayama: "A novel method based on artificial neural networks for optimizing transdermal drug delivery systems, Handbook of Pharmaceutical Controlled Release Technology"Marcel Dekker, Inc.. 890 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. H. Hwang, Y. Maitani, K. Takayama and T. Nagai: "High entrapment of insulin and bovine serum albumin into neutral and positively-charged liposomes by the remote loading method"Chem. Pharm. Bull.. 48. 325-329 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Onuki, M. Morishita, K. Takayama, S. Tokiwa, Y. Chiba, K. Isowa and T. Nagai: "In vivo effects of highly purified docosahexaenoic acid on rectal insulin absorption"Int. J. Pharm.. 198. 147-156 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Obata, H. Sato, C. J. Li, K. Takayama, K. Higashiyama, T. Nagai and K. Isowa: "Effect of synthesized cyclohexanol derivatives using L-menthol as a lead compound on the percutaneous absorption of ketoprofen"Int. J. Pharm.. 198. 191-200 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Maitani, K. Nakamura, H. Suenaga, K. Kamata, K. Takayama and T. Nagai: "The enhancing effect of soybean-derived sterylglucoside and β-sitosterol β-D-glucoside on nasal absorption in rabbits"Int. J. Pharm.. 200. 17-26 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Obata, T. Sesumi, K. Takayama, K. Isowa, S. Grosh, S. Wick, R. Sitz and T. Naga: "Evaluation of skin damage caused by percutaneous absorption enhancers using fractal analysis"J. Pharm. Sci.. 89. 556-561 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Muramatsu, T. Masumizu, Y. Maitani, S. H. Hwang, M. Kohno, K. Takayama and T. Nagai: "Electron spin resonance studies of dipalmitoylphosphatidylcholine liposomes containing soybean-derived sterylglucoside"Chem. Pharm. Bull.. 48. 610-613 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Takayama, A. Morva, M. Fujikawa, Y. Hattori, Y. Obata and T. Nagai: "Formula optimization of theophylline tablet based on artificial neural networks"J. Controlled Rel.. 68. 145-186 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. P. Wang, Y. Maitani, K. Takayama and T. Nagai: "In vivo evaluation of doxorubicin carried with long circulating and remote loading proliposome"Int. J. Pharm.. 203. 61-69 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Kajita, M. Morishita, K. Takayama, Y. Chiba, S. Tokiwa and T. Nagai: "Enhanced enteral bioavailability of vancomycin uisng water-in-oil-in-water multiple emulsion incorporating highly purified unsaturated fatty acid"J. Pharm. Sci.. 89. 1243-1252 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Maitani, S. H. Hwang, S. Tanaka, K. Takayama and T. Nagai: "Physicochemical characteristics and transfection efficiency of DNA in liposomes with soybean-derived sterylglucoside into HepG2 cells"J. Pharm. Sci. Technol, Jpn.. 61. 1-10 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Morishita, J. M. Barichello, K. Takayama, Y. Chiba, S. Tokiwa and T. Nagai: "Pluronic F-127 gels incorporating highly purified unsaturated fatty acids for buccal delivery of insulin"Int. J. Pharm.. 212. 289-293 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Obata, C. J. Li, M. Fujikawa, K. Takayama, H. Sato, K. Higashiyama, K. Isowa and T. Nagai: "Evaluation and structure-activity relationship of synthesized cyclohexanol derivatives on percutaneous absorption of ketoprofen using artificial neural network"Int. J. Pharm.. 212. 223-231 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. P. Wang, Y. Maitani, K. Takayama and T. Nagai: "Pharmacokinetics and antitumor effect of doxorubicin carried by stealth and remote loading proliposome"Pharm. Res.. 17. 782-787 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Maitani, H. Soeda, J. P. Wang and K. Takayama: "Modified ethanol injection method for liposomes containing -sitosterol -D-glucoside"J. Liposome Research. 11. 115-125 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Maitani, K. Kawano, K. Yamada, T. Nagai and K. Takayama: "Efficency of liposomes surface-modified with soybean-derived sterylglucoside as a liver targeting carrier in HepG2 cells"J. Controlled Rel.. 75. 137-142 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C. J. Li, K. Higashiyama, Y. Yoshimura, T. Nagai, K. Takayama and Y. Obata: "Promoting mechanism of menthol derivatives, 1-O-ethyl-3-buthylcylohexanol, on the percutaneous absorption of ketoprofen"Biol. Pharm. Bull.. 24. 1044-1048 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] P. C. Wu, Y. Obata, M. Fujikawa, C. J. Li, K. Higashiyama and K. Takayama: "Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer"J. Pharm. Sci.. 90. 1004-1014 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. H. Hwang, K. Hayashi, K. Takayama and Y. Maitani: "Liver-targeted gene transfer into a human hepattoblastoma cell line and in vivo by sterylglucoside-containg cationic liposomes"Gene Therapy. 8. 1276-1280 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Watanabe, T. Hasegawa, H. Takahashi, T. Ishibashi, K. Takayama and K.Sugibayashi: "Utility of the three-dimensional cultured human skin model as a tool to evaluate skin permeation of drugs"Altern. Animal Test. Experiment.. 8. 1-14 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Nakamura, Y. Maitani and K. Takayama: "Enhancement of FITC-dextran absorption via nasal mucosa by nanoparticles based on β-sitosterol β-D-glucoside and its aglycon"S.T.P. Pharm., Sci.. 12. 63-68 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Nakamura, Y. Maitani and K. Takayama: "The enhancing effect of nasal absorption of FITC-dextran 4,400 by β-sitosterol β-D-glicoside in rabbits"J. Controlled Rel.. 79. 147-155 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. P. Wang, Y. Maitani and K. Takayama: "Antitumor effects and pharmacokinetics of aclacinomycin A carried by injectable emulsions composed of vitamin E, cholesterol and PEG-lipid"J. Pharm. Sci.. 91. 1128-1134 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Kawano, K. Nakamura, K. Hayashi, T. Nagai, K. Takayama and Y. Maitani: "Liver targeting liposomes containing β-sitosterol glucoside with regard to penetration-enhancing effect on HepG2 cells"Biol. Pharm. Bull.. 25. 766-770 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Kanebako, T. Inagi and K. Takayama: "Transdermal delivery of indomethacin by iontophoresis"Biol. Pharm. Bull.. 25. 779-782 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Sudo, U. Iwase, K. Higashiyama, K. Kakuno, F. Miyasaka, T. Meguro and K. Takayama: "Elevation of plasma levels of L-dopa in transdermal administration of L-dopa-butylester in rats"Drug Dev. Ind. Pharm.. 28. 59-65 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Morishita, A. M. Lowman, K. Takayama, T. Nagai and N. A. Peppas: "Elucidation of the mechanism of incorporation of insulin in controlled irelease systems based on complexation polymers"J. Controlled Rel.. 81. 25-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Tsutsumi, Y. Obata, T. Nagai, T. Loftsson and K. Takayama: "Buccal absorption of ergotamine tertrate using the bioadhesive tablet system in guinea-pigs"Int. J. Pharm.. 238. 161-170 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Morita, Y. Tsushima, M. Yasui, R. Termoz, J. Ajioka and K. Takayama: "Evaluation of the disintegration time of rapidly disintegrating tablets via a movel method utilizing a CCD camera"Chem. Pharm. Bull.. 50. 1181-1186 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Asai, M. Morishita, H. Katsuta, S. Hosoda, K. Shinomiya, M. Noro, T. Nagai and K. Takayama: "The effects of water-soluble cyclodextrine on the histolegical integrity of the rat nasal mucosa"Int. J. Pharm.. 246. 25-35 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Kanebako, T. Inagi and K. Takayama: "Evaluation of skin barrier function using direct current I: Effect of conductivity, voltage, distance between electrodes and electrode area"Biol Pharm. Bull.. 25. 1456-1460 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Kanebako, T. Inagi and K. Takayama: "Evaluation of skin barrier function using direct current II: Effects of duty cycle, waveform, frequency and mode"Biol Pharm. Bull.. 25. 1623-1628 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Nakamura, K. Takayama, T, Nagai and Y. Maitani: "Regional intestinal absorption of FITC-dextran 4,400 with nanoparticles based on β-sitosterol β-D-glucoside in rats"J. Pharm, Sci.. 92. 311-318 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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