Physiological Bicarbonate Buffers: Stablisation and Use as Dissolution Media for Modified Release Systems

Hamid Merchant, Hala M. Fadda, Basel T. Arafat, Abdul W. Basit

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Bicarbonate media are reflective of the ionic composition and buffer capacity of small intestinal luminal fluids. Here we investigate methods to stabilise bicarbonate buffers which can be readily applied to USP-II dissolution apparatus. The in vitro drug release behaviour of three enteric coated mesalazine (mesalamine) products is investigated. Asacol® 400 mg and Asacol® 800 mg (Asacol® HD) and the new generation, high dose (1200 mg) delayed and sustained release formulation, Mezavant® (Lialda®), are compared in pH 7.4 Krebs bicarbonate and phosphate buffers. Bicarbonate stabilisation was achieved by: continuous sparging of the medium with 5% CO2(g), application of a layer of liquid paraffin above the medium, or a specially designed in-house seal device that prevents CO2(g) loss. Each of the products displayed a delayed onset of drug release in physiological bicarbonate media compared to phosphate buffer. Moreover, Mezavant® displayed a zero-order, sustained release profile in phosphate buffer; in bicarbonate media, however, this slow drug release was no longer apparent and a profile similar to that of Asacol® 400 mg was observed. These similar release patterns of Asacol® 400 mg and Mezavant® displayed in bicarbonate media are in agreement with their pharmacokinetic profiles in humans. Bicarbonate media provide a better prediction of the in vivo behaviour of the mesalazine preparations investigated.

LanguageEnglish
Pages56-60
Number of pages5
JournalInternational Journal of Pharmaceutics
Volume382
Issue number1-2
DOIs
Publication statusPublished - 1 Dec 2009
Externally publishedYes

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Mesalamine
Bicarbonates
Buffers
Phosphates
Mineral Oil
Pharmacokinetics
Equipment and Supplies

Cite this

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title = "Physiological Bicarbonate Buffers: Stablisation and Use as Dissolution Media for Modified Release Systems",
abstract = "Bicarbonate media are reflective of the ionic composition and buffer capacity of small intestinal luminal fluids. Here we investigate methods to stabilise bicarbonate buffers which can be readily applied to USP-II dissolution apparatus. The in vitro drug release behaviour of three enteric coated mesalazine (mesalamine) products is investigated. Asacol{\circledR} 400 mg and Asacol{\circledR} 800 mg (Asacol{\circledR} HD) and the new generation, high dose (1200 mg) delayed and sustained release formulation, Mezavant{\circledR} (Lialda{\circledR}), are compared in pH 7.4 Krebs bicarbonate and phosphate buffers. Bicarbonate stabilisation was achieved by: continuous sparging of the medium with 5{\%} CO2(g), application of a layer of liquid paraffin above the medium, or a specially designed in-house seal device that prevents CO2(g) loss. Each of the products displayed a delayed onset of drug release in physiological bicarbonate media compared to phosphate buffer. Moreover, Mezavant{\circledR} displayed a zero-order, sustained release profile in phosphate buffer; in bicarbonate media, however, this slow drug release was no longer apparent and a profile similar to that of Asacol{\circledR} 400 mg was observed. These similar release patterns of Asacol{\circledR} 400 mg and Mezavant{\circledR} displayed in bicarbonate media are in agreement with their pharmacokinetic profiles in humans. Bicarbonate media provide a better prediction of the in vivo behaviour of the mesalazine preparations investigated.",
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Physiological Bicarbonate Buffers : Stablisation and Use as Dissolution Media for Modified Release Systems. / Merchant, Hamid; Fadda, Hala M.; Arafat, Basel T.; Basit, Abdul W.

In: International Journal of Pharmaceutics, Vol. 382, No. 1-2, 01.12.2009, p. 56-60.

Research output: Contribution to journalArticle

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