The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method

Kelly Etherson, Gavin Halbert, Moira Elliott

Research output: Contribution to journalArticle

Abstract

Objectives: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl--cyclodextrin (HPCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method.
Methods: The drug’s kinetic and intrinsic aqueous solubility was measured in the presence of increasing excipient concentrations using the CheqSol solubility method. Experimental data for example rate of change of pH with time was also examined to determine excipient induced parachute effects and influence on precipitation rates.
Key Findings: The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters for example the precipitation pH or percentage ionized drug at the precipitation point which provide further information on the excipient induced changes in precipitation performance.
Conclusion: This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behavior of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.
LanguageEnglish
Pages1131-1142
Number of pages12
JournalJournal of Pharmacy and Pharmacology
Volume68
Issue number9
Early online date1 Jul 2016
DOIs
Publication statusPublished - 30 Sep 2016

Fingerprint

Excipients
Solubility
Poloxamer
Gliclazide
Atenolol
Ibuprofen
Cyclodextrins
Propranolol
Pharmaceutical Preparations
Area Under Curve
Pharmacokinetics

Keywords

  • non-ionisable excipients
  • supersaturation
  • precipitation kinetics
  • ibuprofen
  • gliclazide
  • propranolol
  • atenolol
  • kinetic solubilities
  • intrinsic solubilities
  • ionisable drugs

Cite this

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title = "The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method",
abstract = "Objectives: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl--cyclodextrin (HPCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method. Methods: The drug’s kinetic and intrinsic aqueous solubility was measured in the presence of increasing excipient concentrations using the CheqSol solubility method. Experimental data for example rate of change of pH with time was also examined to determine excipient induced parachute effects and influence on precipitation rates. Key Findings: The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters for example the precipitation pH or percentage ionized drug at the precipitation point which provide further information on the excipient induced changes in precipitation performance. Conclusion: This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behavior of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.",
keywords = "non-ionisable excipients, supersaturation, precipitation kinetics, ibuprofen, gliclazide, propranolol, atenolol, kinetic solubilities, intrinsic solubilities, ionisable drugs",
author = "Kelly Etherson and Gavin Halbert and Moira Elliott",
note = "This is the peer reviewed version of the following article: Etherson, K., Halbert, G., & Elliott, M. (2016). The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method. Journal of Pharmacy and Pharmacology, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jphp.12602. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.",
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The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method. / Etherson, Kelly; Halbert, Gavin; Elliott, Moira.

In: Journal of Pharmacy and Pharmacology, Vol. 68, No. 9, 30.09.2016, p. 1131-1142.

Research output: Contribution to journalArticle

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AU - Etherson, Kelly

AU - Halbert, Gavin

AU - Elliott, Moira

N1 - This is the peer reviewed version of the following article: Etherson, K., Halbert, G., & Elliott, M. (2016). The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method. Journal of Pharmacy and Pharmacology, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/jphp.12602. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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Y1 - 2016/9/30

N2 - Objectives: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl--cyclodextrin (HPCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method. Methods: The drug’s kinetic and intrinsic aqueous solubility was measured in the presence of increasing excipient concentrations using the CheqSol solubility method. Experimental data for example rate of change of pH with time was also examined to determine excipient induced parachute effects and influence on precipitation rates. Key Findings: The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters for example the precipitation pH or percentage ionized drug at the precipitation point which provide further information on the excipient induced changes in precipitation performance. Conclusion: This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behavior of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.

AB - Objectives: The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl--cyclodextrin (HPCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method. Methods: The drug’s kinetic and intrinsic aqueous solubility was measured in the presence of increasing excipient concentrations using the CheqSol solubility method. Experimental data for example rate of change of pH with time was also examined to determine excipient induced parachute effects and influence on precipitation rates. Key Findings: The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters for example the precipitation pH or percentage ionized drug at the precipitation point which provide further information on the excipient induced changes in precipitation performance. Conclusion: This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behavior of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.

KW - non-ionisable excipients

KW - supersaturation

KW - precipitation kinetics

KW - ibuprofen

KW - gliclazide

KW - propranolol

KW - atenolol

KW - kinetic solubilities

KW - intrinsic solubilities

KW - ionisable drugs

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EP - 1142

JO - Journal of Pharmacy and Pharmacology

T2 - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 9

ER -