Rational use of antioxidants in solid oral pharmaceutical preparations
Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.
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Universidade de São Paulo, Faculdade de Ciências Farmacêuticas
2012
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oai:scielo:S1984-825020120003000072012-10-18Rational use of antioxidants in solid oral pharmaceutical preparationsCelestino,Maísa TeodoroMagalhães,Uiaran de OliveiraFraga,Aline Guerra ManssourCarmo,Flávia Almada doLione,VivianeCastro,Helena CarlaSousa,Valeria Pereira deRodrigues,Carlos RangelCabral,Lucio Mendes Antioxidants/rational use Excipients/evaluation Butylated hydroxyanisole/rational use Butylated hydroxytoluene/rational use Sodium metabisulfite/rational use Propyl gallate/rational use Cysteine/rational use Simvastatin/tablets Simvastatin/evaluation Ketoconazole/tablets Ketoconazole/evaluation Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations.info:eu-repo/semantics/openAccessUniversidade de São Paulo, Faculdade de Ciências FarmacêuticasBrazilian Journal of Pharmaceutical Sciences v.48 n.3 20122012-09-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502012000300007en10.1590/S1984-82502012000300007 |
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Celestino,Maísa Teodoro Magalhães,Uiaran de Oliveira Fraga,Aline Guerra Manssour Carmo,Flávia Almada do Lione,Viviane Castro,Helena Carla Sousa,Valeria Pereira de Rodrigues,Carlos Rangel Cabral,Lucio Mendes |
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Celestino,Maísa Teodoro Magalhães,Uiaran de Oliveira Fraga,Aline Guerra Manssour Carmo,Flávia Almada do Lione,Viviane Castro,Helena Carla Sousa,Valeria Pereira de Rodrigues,Carlos Rangel Cabral,Lucio Mendes Rational use of antioxidants in solid oral pharmaceutical preparations |
author_facet |
Celestino,Maísa Teodoro Magalhães,Uiaran de Oliveira Fraga,Aline Guerra Manssour Carmo,Flávia Almada do Lione,Viviane Castro,Helena Carla Sousa,Valeria Pereira de Rodrigues,Carlos Rangel Cabral,Lucio Mendes |
author_sort |
Celestino,Maísa Teodoro |
title |
Rational use of antioxidants in solid oral pharmaceutical preparations |
title_short |
Rational use of antioxidants in solid oral pharmaceutical preparations |
title_full |
Rational use of antioxidants in solid oral pharmaceutical preparations |
title_fullStr |
Rational use of antioxidants in solid oral pharmaceutical preparations |
title_full_unstemmed |
Rational use of antioxidants in solid oral pharmaceutical preparations |
title_sort |
rational use of antioxidants in solid oral pharmaceutical preparations |
description |
Antioxidants are currently used as efficient excipients that delay or inhibit the oxidation process of molecules. Excipients are often associated with adverse reactions. Stability studies can guide the search for solutions that minimize or delay the processes of degradation. The ability to predict oxidation reactions in different drugs is important. Methods: This study was conducted to assess the rational use of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite (SMB), propyl gallate (PG) and cysteine (CYS) in tablet formulations of simvastatin and ketoconazole. These antioxidants were evaluated according to stability parameters and the relationship between efficiency of the antioxidant and chemical structure of the drugs. Results were compared with DPPH tests and computational simulations. BHT was most efficient regarding simvastatin stability, and the most effective BHT concentrations for maintaining stability were 0.5 and 0.1%. In relation to ketoconazole, SMB was most efficient for maintaining content and dissolution profile. The evaluation by DPPH showed that the largest percentage of absorbance reduction was observed for PG, while SMB proved most efficient and had lower consumption of DPPH. The same pattern was observed, albeit with lower efficiency, for the other lipophilic antioxidants such as BHT and BHA. The results of the molecular modeling study demonstrated that electronic properties obtained were correlated with antioxidant activity in solution, being useful for the rational development of liquid pharmaceutical formulations but not for solid oral formulations. This study demonstrated the importance of considering stability parameters and molecular modeling to elucidate the chemical phenomena involved in antioxidant activity, being useful for the rational use of antioxidants in the development of pharmaceutical formulations. |
publisher |
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas |
publishDate |
2012 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502012000300007 |
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