Accelerating the dissolution of enteric coatings in the upper small intestine: Evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release

F. J. Varum, Hamid Merchant, A. Goyanes, V. Zboranová, A. W. Basit

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ system, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5mg/cm2 of partially neutralized EUDRAGIT® L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT® L 30 D-55 was applied at 5mg/cm2. For comparison purposes, a standard single layer of EUDRAGIT® L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1M HCl for 2h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT® L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75min in buffer, whereas release from the EUDRAGIT® L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages in the development of dosage forms designed to release in the upper small intestine.
LanguageEnglish
Pages172-177
Number of pages6
JournalInternational Journal of Pharmaceutics
Volume468
Issue number1-2
DOIs
Publication statusPublished - Jul 2014

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L 30
Bicarbonates
Small Intestine
Buffers
Tablets
Dosage Forms
Prednisolone
Drug Liberation
Phosphates

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title = "Accelerating the dissolution of enteric coatings in the upper small intestine: Evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release",
abstract = "Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ system, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5mg/cm2 of partially neutralized EUDRAGIT{\circledR} L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT{\circledR} L 30 D-55 was applied at 5mg/cm2. For comparison purposes, a standard single layer of EUDRAGIT{\circledR} L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1M HCl for 2h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT{\circledR} L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75min in buffer, whereas release from the EUDRAGIT{\circledR} L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages in the development of dosage forms designed to release in the upper small intestine.",
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Accelerating the dissolution of enteric coatings in the upper small intestine : Evolution of a novel pH 5.6 bicarbonate buffer system to assess drug release. / Varum, F. J. ; Merchant, Hamid; Goyanes, A.; Zboranová, V.; Basit, A. W. .

In: International Journal of Pharmaceutics, Vol. 468, No. 1-2, 07.2014, p. 172-177.

Research output: Contribution to journalArticle

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T1 - Accelerating the dissolution of enteric coatings in the upper small intestine

T2 - International Journal of Pharmaceutics

AU - Varum, F. J.

AU - Merchant, Hamid

AU - Goyanes, A.

AU - Zboranová, V.

AU - Basit, A. W.

PY - 2014/7

Y1 - 2014/7

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AB - Despite rapid dissolution in compendial phosphate buffers, gastro resistant (enteric coated) products can take up to 2h to disintegrate in the human small intestine, which clearly highlights the inadequacy of the in vitro test method to predict in vivo behaviour of these formulations. The aim of this study was to establish the utility of a novel pH 5.6 bicarbonate buffer, stabilized by an Auto pH™ system, as a better surrogate of the conditions of the proximal small intestine to investigate the dissolution behaviour of standard and accelerated release enteric double coating formulations. Prednisolone tablets were coated with 3 or 5mg/cm2 of partially neutralized EUDRAGIT® L 30 D-55, HP-55 or HPMC adjusted to pH 6 or 8. An outer layer of EUDRAGIT® L 30 D-55 was applied at 5mg/cm2. For comparison purposes, a standard single layer of EUDRAGIT® L 30 D-55 was applied to the tablets. Dissolution was carried out using USP II apparatus in 0.1M HCl for 2h, followed by pH 5.6 bicarbonate buffer. EUDRAGIT® L 30 D-55 single-coated tablets showed a slow drug release with a lag time of 75min in buffer, whereas release from the EUDRAGIT® L 30 D-55 double-coated tablets was accelerated. These in vitro lag times closely match the in vivo disintegration times for these coated tablets reported previously. Drug release was further accelerated from modified double coatings, particularly in the case of coatings with a thinner inner layer of HP-55 or HPMC (pH 8 and KH2PO4). This study confirms that the pH 5.6 bicarbonate buffer system offers significant advantages in the development of dosage forms designed to release in the upper small intestine.

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M3 - Article

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SP - 172

EP - 177

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

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