Drug Stability

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Concepcion Domingo - One of the best experts on this subject based on the ideXlab platform.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug–matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • impregnation of a biocompatible polymer aided by supercritical co2 evaluation of Drug Stability and Drug matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana M Lopezperiago, Jesús Saurina, A. Argemí, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Carlos A Garciagonzalez, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug-matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO2) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time. © 2008 Elsevier B.V. All rights reserved.

Daniel E Otzen - One of the best experts on this subject based on the ideXlab platform.

  • Protein Drug Stability: a formulation challenge
    Nature Reviews Drug Discovery, 2005
    Co-Authors: Sven Frokjaer, Daniel E Otzen
    Abstract:

    Recombinantly expressed proteins are increasingly important in Drug therapy. This makes it crucial to assess how their properties as proteins affect Drug efficacy, targeting and side effects, as well as the ability to survive long-term storage. Amino-acid substitutions have led to therapeutically improved variants of, for example, insulin and interleukin-2, but modifications such as acylation and PEGylation can be just as effective, by causing a decrease in the clearing rate and reducing immunogenicity. Aggregation and misfolding is a fundamental issue in the long-term storage of protein therapeutics before administration. Although the mechanisms of aggregation are complex and can differ between even closely related proteins, methods have been developed to predict how amino-acid substitutions can affect this process. An easier approach might be to modify Drug formulations. Simple additives, such as detergents, amino-acid pairs or cyclodextrins, can markedly reduce aggregation. Furthermore, judicious use of lyophilization can also provide a very reliable way to extend shelf-life. The increasing use of recombinantly expressed therapeutic proteins in the pharmaceutical industry has highlighted issues such as their Stability during long-term storage and means of efficacious delivery that avoid adverse immunogenic side effects. Controlled chemical modifications, such as substitutions, acylation and PEGylation, have fulfilled some but not all of their promises, while hydrogels and lipid-based formulations could well be developed into generic delivery systems. Strategies to curb the aggregation and misfolding of proteins during storage are likely to benefit from the recent surge of interest in protein fibrillation. This might in turn lead to generally accepted guidelines and tests to avoid unforeseen adverse effects in Drug delivery.

  • Protein Drug Stability: A formulation challenge
    Nature Reviews Drug Discovery, 2005
    Co-Authors: Sven Frokjaer, Daniel E Otzen
    Abstract:

    The increasing use of recombinantly expressed therapeutic proteins in the pharmaceutical industry has highlighted issues such as their Stability during long-term storage and means of efficacious delivery that avoid adverse immunogenic side effects. Controlled chemical modifications, such as substitutions, acylation and PEGylation, have fulfilled some but not all of their promises, while hydrogels and lipid-based formulations could well be developed into generic delivery systems. Strategies to curb the aggregation and misfolding of proteins during storage are likely to benefit from the recent surge of interest in protein fibrillation. This might in turn lead to generally accepted guidelines and tests to avoid unforeseen adverse effects in Drug delivery.

Sven Frokjaer - One of the best experts on this subject based on the ideXlab platform.

  • Protein Drug Stability: a formulation challenge
    Nature Reviews Drug Discovery, 2005
    Co-Authors: Sven Frokjaer, Daniel E Otzen
    Abstract:

    Recombinantly expressed proteins are increasingly important in Drug therapy. This makes it crucial to assess how their properties as proteins affect Drug efficacy, targeting and side effects, as well as the ability to survive long-term storage. Amino-acid substitutions have led to therapeutically improved variants of, for example, insulin and interleukin-2, but modifications such as acylation and PEGylation can be just as effective, by causing a decrease in the clearing rate and reducing immunogenicity. Aggregation and misfolding is a fundamental issue in the long-term storage of protein therapeutics before administration. Although the mechanisms of aggregation are complex and can differ between even closely related proteins, methods have been developed to predict how amino-acid substitutions can affect this process. An easier approach might be to modify Drug formulations. Simple additives, such as detergents, amino-acid pairs or cyclodextrins, can markedly reduce aggregation. Furthermore, judicious use of lyophilization can also provide a very reliable way to extend shelf-life. The increasing use of recombinantly expressed therapeutic proteins in the pharmaceutical industry has highlighted issues such as their Stability during long-term storage and means of efficacious delivery that avoid adverse immunogenic side effects. Controlled chemical modifications, such as substitutions, acylation and PEGylation, have fulfilled some but not all of their promises, while hydrogels and lipid-based formulations could well be developed into generic delivery systems. Strategies to curb the aggregation and misfolding of proteins during storage are likely to benefit from the recent surge of interest in protein fibrillation. This might in turn lead to generally accepted guidelines and tests to avoid unforeseen adverse effects in Drug delivery.

  • Protein Drug Stability: A formulation challenge
    Nature Reviews Drug Discovery, 2005
    Co-Authors: Sven Frokjaer, Daniel E Otzen
    Abstract:

    The increasing use of recombinantly expressed therapeutic proteins in the pharmaceutical industry has highlighted issues such as their Stability during long-term storage and means of efficacious delivery that avoid adverse immunogenic side effects. Controlled chemical modifications, such as substitutions, acylation and PEGylation, have fulfilled some but not all of their promises, while hydrogels and lipid-based formulations could well be developed into generic delivery systems. Strategies to curb the aggregation and misfolding of proteins during storage are likely to benefit from the recent surge of interest in protein fibrillation. This might in turn lead to generally accepted guidelines and tests to avoid unforeseen adverse effects in Drug delivery.

Jean-michel Andanson - One of the best experts on this subject based on the ideXlab platform.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug–matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • impregnation of a biocompatible polymer aided by supercritical co2 evaluation of Drug Stability and Drug matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana M Lopezperiago, Jesús Saurina, A. Argemí, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Carlos A Garciagonzalez, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug-matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO2) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time. © 2008 Elsevier B.V. All rights reserved.

Jesús Saurina - One of the best experts on this subject based on the ideXlab platform.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug–matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • impregnation of a biocompatible polymer aided by supercritical co2 evaluation of Drug Stability and Drug matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana M Lopezperiago, Jesús Saurina, A. Argemí, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Carlos A Garciagonzalez, Concepcion Domingo
    Abstract:

    Abstract Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO 2 ) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1 H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time.

  • Impregnation of a biocompatible polymer aided by supercritical CO2: Evaluation of Drug Stability and Drug-matrix interactions
    Journal of Supercritical Fluids, 2009
    Co-Authors: Ana López-periago, Jesús Saurina, A. Argemí, Carlos A. García-gonzález, Sergei G. Kazarian, V Fernandez, Jean-michel Andanson, Concepcion Domingo
    Abstract:

    Poly (methyl methacrylate) (PMMA) was loaded with 2-acetyloxy-4-(trifluoromethyl) benzoic acid (triflusal) by using a supercritical carbon dioxide (scCO2) impregnation method. The main objective of this work was to provide information for the infusion of additives into nonporous polymeric substrates for design of sustained release systems. Chemical and H-bonding interactions between the matrix and the infused Drug were evaluated together with the impregnated Drug Stability. The composition of the obtained systems was characterized by 1H magnetic nuclear resonance and liquid chromatography. The microstructure of the impregnated matrix was studied using thermal analysis. The affinity of the solute to the polymer was explored via attenuated total reflection (ATR)-FTIR and Raman spectroscopies. Finally, an in vitro elution method coupled with high-performance liquid chromatography was used to evaluate the release behavior of prepared formulations. Loadings of ca. 20 wt% of active agent in PMMA were obtained, while the Drug crystallization was avoided. From a pharmaceutical point of view, the impregnated samples had an excellent potential for the preparation of sustained formulations, since the delivery profiles were consistent with keeping stable levels of the Drug over a long period of time. © 2008 Elsevier B.V. All rights reserved.