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In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms
The objective of this study was to compare the in vitro behavior of four long-acting subcutaneous risperidone formulations with in vivo performance, with the intent of establishing an IVIVC. Two copolymers of PLGA (50:50 and 75:25) were used to prepare four microsphere formulations of risperidone, a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301450/ https://www.ncbi.nlm.nih.gov/pubmed/29470771 http://dx.doi.org/10.1007/s40204-014-0029-4 |
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author | D’Souza, Susan Faraj, Jabar A. Giovagnoli, Stefano DeLuca, Patrick P. |
author_facet | D’Souza, Susan Faraj, Jabar A. Giovagnoli, Stefano DeLuca, Patrick P. |
author_sort | D’Souza, Susan |
collection | PubMed |
description | The objective of this study was to compare the in vitro behavior of four long-acting subcutaneous risperidone formulations with in vivo performance, with the intent of establishing an IVIVC. Two copolymers of PLGA (50:50 and 75:25) were used to prepare four microsphere formulations of risperidone, an atypical antipsychotic. In vitro behavior was assessed at the physiological temperature (37 °C) using the ‘modified dialysis’ technique. The in vitro release profile demonstrated rank order behavior with Formulations A and B, prepared using the 50:50 copolymer, exhibiting rapid drug release, while Formulations C and D, prepared using 75:25 PLGA, released drug in a slower manner. In vivo profiles were obtained by two approaches, i.e., deconvolution using the Nelson–Wagner equation (the FDA recommended approach) and using fractional AUC. With both in vivo approaches, the 50:50 PLGA preparations released drug faster than the 75:25 PLGA microspheres, exhibiting the same rank order observed in vitro. Additionally, profiles for the four formulations obtained using the deconvolution approach were nearly superimposable with fractional AUC, implying that the latter procedure could be used as a substitute for the Nelson–Wagner method. A comparison of drug release profiles for the four formulations revealed that in three of the four formulations, in vivo release was slightly faster than that in vitro, but the results were not statistically significant (P > 0.0001). An excellent linear correlation (R(2) values between 0.97 and 0.99) was obtained when % in vitro release for each formulation was compared with its corresponding in vivo release profile, obtained by using fraction absorbed (Nelson–Wagner method) or fractional AUC. In summary, using the four formulations that exhibited different release rates, a Level A IVIVC was established using the FDA-recommended deconvolution method and fractional AUC approach. The excellent relationship between in vitro drug release and the amount of drug absorbed in vivo in this study was corroborated by the nearly 1:1 correlation (R(2) greater than 0.97) between in vitro release and in vivo performance. Thus, the results of the current study suggest that proper selection of an in vitro method to assess drug release from long-acting injectables will aid in obtaining a Level A IVIVC. |
format | Online Article Text |
id | pubmed-5301450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-53014502017-02-24 In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms D’Souza, Susan Faraj, Jabar A. Giovagnoli, Stefano DeLuca, Patrick P. Prog Biomater Original Research The objective of this study was to compare the in vitro behavior of four long-acting subcutaneous risperidone formulations with in vivo performance, with the intent of establishing an IVIVC. Two copolymers of PLGA (50:50 and 75:25) were used to prepare four microsphere formulations of risperidone, an atypical antipsychotic. In vitro behavior was assessed at the physiological temperature (37 °C) using the ‘modified dialysis’ technique. The in vitro release profile demonstrated rank order behavior with Formulations A and B, prepared using the 50:50 copolymer, exhibiting rapid drug release, while Formulations C and D, prepared using 75:25 PLGA, released drug in a slower manner. In vivo profiles were obtained by two approaches, i.e., deconvolution using the Nelson–Wagner equation (the FDA recommended approach) and using fractional AUC. With both in vivo approaches, the 50:50 PLGA preparations released drug faster than the 75:25 PLGA microspheres, exhibiting the same rank order observed in vitro. Additionally, profiles for the four formulations obtained using the deconvolution approach were nearly superimposable with fractional AUC, implying that the latter procedure could be used as a substitute for the Nelson–Wagner method. A comparison of drug release profiles for the four formulations revealed that in three of the four formulations, in vivo release was slightly faster than that in vitro, but the results were not statistically significant (P > 0.0001). An excellent linear correlation (R(2) values between 0.97 and 0.99) was obtained when % in vitro release for each formulation was compared with its corresponding in vivo release profile, obtained by using fraction absorbed (Nelson–Wagner method) or fractional AUC. In summary, using the four formulations that exhibited different release rates, a Level A IVIVC was established using the FDA-recommended deconvolution method and fractional AUC approach. The excellent relationship between in vitro drug release and the amount of drug absorbed in vivo in this study was corroborated by the nearly 1:1 correlation (R(2) greater than 0.97) between in vitro release and in vivo performance. Thus, the results of the current study suggest that proper selection of an in vitro method to assess drug release from long-acting injectables will aid in obtaining a Level A IVIVC. Springer Berlin Heidelberg 2014-12-02 /pmc/articles/PMC5301450/ /pubmed/29470771 http://dx.doi.org/10.1007/s40204-014-0029-4 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Research D’Souza, Susan Faraj, Jabar A. Giovagnoli, Stefano DeLuca, Patrick P. In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title | In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title_full | In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title_fullStr | In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title_full_unstemmed | In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title_short | In vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
title_sort | in vitro–in vivo correlation from lactide-co-glycolide polymeric dosage forms |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301450/ https://www.ncbi.nlm.nih.gov/pubmed/29470771 http://dx.doi.org/10.1007/s40204-014-0029-4 |
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