Predicting the gastrointestinal behaviour of modified-release products: Utility of a novel dynamic dissolution test apparatus involving the use of bicarbonate buffers

Hamid Merchant, Alvaro Goyanes, Narendra Parashar, Abdul W. Basit

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The establishment of physiologically relevant in vitro-in vivo correlations (IV-IVCs) is key for any biorelevant dissolution test. Historically, bicarbonate buffers have produced better correlations than compendial phosphate buffered media, though such tests are usually performed at a constant pH experiment, overlooking the notion that the pH of the luminal fluids is variable and fluctuating. In this work, we have devised a dynamic dissolution test method employing a physiological bicarbonate buffer under pH conditions of the proximal gut in order to assess the dissolution behaviour of various enteric polymer-coated (gastro-resistant) prednisolone tablets. The pH of the media is modulated and controlled by an Auto pH System™ which exploits the physiological equilibria between [H2CO3] and [HCO3-], to match it to the aboral change in pH with transit of the dosage form through the proximal small intestine (from pH 5.6 up to 6.8). The lag time values for an accelerated release and standard EUDRAGIT® L30D-55 coated formulation (25min and 60min, respectively) were close to the previously reported initial tablet disintegration time data obtained in-vivo by γ-scintigraphy (28min and 66min, respectively). Dissolution of alternative delayed release coated products was also better discriminated in the dynamic buffer system. These data confirm the dynamic dissolution system provides a robust and reliable platform to predict the in vivo fate of oral products in a laboratory setting.
LanguageEnglish
Pages585-591
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume475
Issue number1-2
Early online date6 Sep 2014
DOIs
Publication statusPublished - 20 Nov 2014
Externally publishedYes

Fingerprint

Bicarbonates
Buffers
Tablets
Dosage Forms
Prednisolone
Radionuclide Imaging
Small Intestine
Polymers
Phosphates

Cite this

@article{9ee0f607354d4d7988760132b26f1861,
title = "Predicting the gastrointestinal behaviour of modified-release products: Utility of a novel dynamic dissolution test apparatus involving the use of bicarbonate buffers",
abstract = "The establishment of physiologically relevant in vitro-in vivo correlations (IV-IVCs) is key for any biorelevant dissolution test. Historically, bicarbonate buffers have produced better correlations than compendial phosphate buffered media, though such tests are usually performed at a constant pH experiment, overlooking the notion that the pH of the luminal fluids is variable and fluctuating. In this work, we have devised a dynamic dissolution test method employing a physiological bicarbonate buffer under pH conditions of the proximal gut in order to assess the dissolution behaviour of various enteric polymer-coated (gastro-resistant) prednisolone tablets. The pH of the media is modulated and controlled by an Auto pH System™ which exploits the physiological equilibria between [H2CO3] and [HCO3-], to match it to the aboral change in pH with transit of the dosage form through the proximal small intestine (from pH 5.6 up to 6.8). The lag time values for an accelerated release and standard EUDRAGIT{\circledR} L30D-55 coated formulation (25min and 60min, respectively) were close to the previously reported initial tablet disintegration time data obtained in-vivo by γ-scintigraphy (28min and 66min, respectively). Dissolution of alternative delayed release coated products was also better discriminated in the dynamic buffer system. These data confirm the dynamic dissolution system provides a robust and reliable platform to predict the in vivo fate of oral products in a laboratory setting.",
keywords = "Physiological bicarbonate buffer, Hydrogen carbonate buffer, Biorelevant dissolution, pH-sensitive polymers, Enteric polymers, Gastro-resistant coatings",
author = "Hamid Merchant and Alvaro Goyanes and Narendra Parashar and Basit, {Abdul W.}",
year = "2014",
month = "11",
day = "20",
doi = "10.1016/j.ijpharm.2014.09.003",
language = "English",
volume = "475",
pages = "585--591",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

Predicting the gastrointestinal behaviour of modified-release products : Utility of a novel dynamic dissolution test apparatus involving the use of bicarbonate buffers. / Merchant, Hamid; Goyanes, Alvaro; Parashar, Narendra; Basit, Abdul W.

In: International Journal of Pharmaceutics, Vol. 475, No. 1-2, 20.11.2014, p. 585-591.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Predicting the gastrointestinal behaviour of modified-release products

T2 - International Journal of Pharmaceutics

AU - Merchant, Hamid

AU - Goyanes, Alvaro

AU - Parashar, Narendra

AU - Basit, Abdul W.

PY - 2014/11/20

Y1 - 2014/11/20

N2 - The establishment of physiologically relevant in vitro-in vivo correlations (IV-IVCs) is key for any biorelevant dissolution test. Historically, bicarbonate buffers have produced better correlations than compendial phosphate buffered media, though such tests are usually performed at a constant pH experiment, overlooking the notion that the pH of the luminal fluids is variable and fluctuating. In this work, we have devised a dynamic dissolution test method employing a physiological bicarbonate buffer under pH conditions of the proximal gut in order to assess the dissolution behaviour of various enteric polymer-coated (gastro-resistant) prednisolone tablets. The pH of the media is modulated and controlled by an Auto pH System™ which exploits the physiological equilibria between [H2CO3] and [HCO3-], to match it to the aboral change in pH with transit of the dosage form through the proximal small intestine (from pH 5.6 up to 6.8). The lag time values for an accelerated release and standard EUDRAGIT® L30D-55 coated formulation (25min and 60min, respectively) were close to the previously reported initial tablet disintegration time data obtained in-vivo by γ-scintigraphy (28min and 66min, respectively). Dissolution of alternative delayed release coated products was also better discriminated in the dynamic buffer system. These data confirm the dynamic dissolution system provides a robust and reliable platform to predict the in vivo fate of oral products in a laboratory setting.

AB - The establishment of physiologically relevant in vitro-in vivo correlations (IV-IVCs) is key for any biorelevant dissolution test. Historically, bicarbonate buffers have produced better correlations than compendial phosphate buffered media, though such tests are usually performed at a constant pH experiment, overlooking the notion that the pH of the luminal fluids is variable and fluctuating. In this work, we have devised a dynamic dissolution test method employing a physiological bicarbonate buffer under pH conditions of the proximal gut in order to assess the dissolution behaviour of various enteric polymer-coated (gastro-resistant) prednisolone tablets. The pH of the media is modulated and controlled by an Auto pH System™ which exploits the physiological equilibria between [H2CO3] and [HCO3-], to match it to the aboral change in pH with transit of the dosage form through the proximal small intestine (from pH 5.6 up to 6.8). The lag time values for an accelerated release and standard EUDRAGIT® L30D-55 coated formulation (25min and 60min, respectively) were close to the previously reported initial tablet disintegration time data obtained in-vivo by γ-scintigraphy (28min and 66min, respectively). Dissolution of alternative delayed release coated products was also better discriminated in the dynamic buffer system. These data confirm the dynamic dissolution system provides a robust and reliable platform to predict the in vivo fate of oral products in a laboratory setting.

KW - Physiological bicarbonate buffer

KW - Hydrogen carbonate buffer

KW - Biorelevant dissolution

KW - pH-sensitive polymers

KW - Enteric polymers

KW - Gastro-resistant coatings

UR - https://www.sciencedirect.com/science/article/pii/S0378517314006462

U2 - 10.1016/j.ijpharm.2014.09.003

DO - 10.1016/j.ijpharm.2014.09.003

M3 - Article

VL - 475

SP - 585

EP - 591

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -