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Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions
In vitro-in vivo correlations (IVIVCs) play an important role in formulation development and drug approval. At the heart of IVIVC is deconvolution, the method of deriving an in vivo “dissolution profile” for comparison with in vitro dissolution data. IVIVCs are generally believed to be possible for...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779109/ https://www.ncbi.nlm.nih.gov/pubmed/26667356 http://dx.doi.org/10.1208/s12248-015-9849-y |
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author | Margolskee, Alison Darwich, Adam S. Galetin, Aleksandra Rostami-Hodjegan, Amin Aarons, Leon |
author_facet | Margolskee, Alison Darwich, Adam S. Galetin, Aleksandra Rostami-Hodjegan, Amin Aarons, Leon |
author_sort | Margolskee, Alison |
collection | PubMed |
description | In vitro-in vivo correlations (IVIVCs) play an important role in formulation development and drug approval. At the heart of IVIVC is deconvolution, the method of deriving an in vivo “dissolution profile” for comparison with in vitro dissolution data. IVIVCs are generally believed to be possible for highly permeable and highly soluble compounds with release/dissolution as the rate-limiting step. In this manuscript, we apply the traditional deconvolution methods, Wagner-Nelson and numerical deconvolution, to profiles simulated using a simplified small intestine absorption and transit model. Small intestinal transit, dissolution, and absorption rate constants are varied across a range of values approximately covering those observed in the literature. IVIVC plots and their corresponding correlation coefficients are analyzed for each combination of parameters to determine the applicability of the deconvolution methods under a range of rate-limiting conditions. For highly absorbed formulations, the correlation coefficients obtained during IVIVC are comparable for both methods and steadily decline with decreasing dissolution rate and increasing transit rate. The applicability of numerical deconvolution to IVIVC is not greatly affected by absorption rate, whereas the applicability of Wagner-Nelson falls when dissolution rate overcomes absorption rate and absorption becomes the rate-limiting step. The discrepancy between the expected and deconvolved input arises from the violation of a key assumption of deconvolution that the unknown input and unit impulse enter the system in the same location. |
format | Online Article Text |
id | pubmed-4779109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-47791092016-03-22 Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions Margolskee, Alison Darwich, Adam S. Galetin, Aleksandra Rostami-Hodjegan, Amin Aarons, Leon AAPS J Research Article In vitro-in vivo correlations (IVIVCs) play an important role in formulation development and drug approval. At the heart of IVIVC is deconvolution, the method of deriving an in vivo “dissolution profile” for comparison with in vitro dissolution data. IVIVCs are generally believed to be possible for highly permeable and highly soluble compounds with release/dissolution as the rate-limiting step. In this manuscript, we apply the traditional deconvolution methods, Wagner-Nelson and numerical deconvolution, to profiles simulated using a simplified small intestine absorption and transit model. Small intestinal transit, dissolution, and absorption rate constants are varied across a range of values approximately covering those observed in the literature. IVIVC plots and their corresponding correlation coefficients are analyzed for each combination of parameters to determine the applicability of the deconvolution methods under a range of rate-limiting conditions. For highly absorbed formulations, the correlation coefficients obtained during IVIVC are comparable for both methods and steadily decline with decreasing dissolution rate and increasing transit rate. The applicability of numerical deconvolution to IVIVC is not greatly affected by absorption rate, whereas the applicability of Wagner-Nelson falls when dissolution rate overcomes absorption rate and absorption becomes the rate-limiting step. The discrepancy between the expected and deconvolved input arises from the violation of a key assumption of deconvolution that the unknown input and unit impulse enter the system in the same location. Springer US 2015-12-14 /pmc/articles/PMC4779109/ /pubmed/26667356 http://dx.doi.org/10.1208/s12248-015-9849-y Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Article Margolskee, Alison Darwich, Adam S. Galetin, Aleksandra Rostami-Hodjegan, Amin Aarons, Leon Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title | Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title_full | Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title_fullStr | Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title_full_unstemmed | Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title_short | Deconvolution and IVIVC: Exploring the Role of Rate-Limiting Conditions |
title_sort | deconvolution and ivivc: exploring the role of rate-limiting conditions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779109/ https://www.ncbi.nlm.nih.gov/pubmed/26667356 http://dx.doi.org/10.1208/s12248-015-9849-y |
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