Az egysúlyi oldhatóság meghatározá sának helyes gyakorlata II. Ionizálható vegyületek pH-függo{combining double acute accent} oldhatóságának vizsgálata

Translated title of the contribution: Good laboratory practice of equilibrium solubility measurement II. Study of pH-dependent solubility of ionizable compounds

Gergely Völgyt, Edit Baka, Márta Kovács, K. Takács-Novák

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In this paper the pH-equilibrium solubility profiles of ionizable drugs are presented. The aim of the present work was to study the validity of the Henderson-Hasselbaich (HH) relationship in the case of structurally diverse weak bases. In the case of monoprotic bases, namely papaverine, promethazine and propafenone the experimental equilibrium solubility data precisely follow the theoretical HH curve until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. It is critical that the pKa value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs.

Original languageHungarian
Pages (from-to)87-95
Number of pages9
JournalActa Pharmaceutica Hungarica
Volume81
Issue number2
Publication statusPublished - 2011

Fingerprint

Solubility
Salts
Propafenone
Promethazine
Papaverine
Fumarates
Pharmaceutical Preparations
Hydrogen
Ions

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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title = "Az egys{\'u}lyi oldhat{\'o}s{\'a}g meghat{\'a}roz{\'a} s{\'a}nak helyes gyakorlata II. Ioniz{\'a}lhat{\'o} vegy{\"u}letek pH-f{\"u}ggo{combining double acute accent} oldhat{\'o}s{\'a}g{\'a}nak vizsg{\'a}lata",
abstract = "In this paper the pH-equilibrium solubility profiles of ionizable drugs are presented. The aim of the present work was to study the validity of the Henderson-Hasselbaich (HH) relationship in the case of structurally diverse weak bases. In the case of monoprotic bases, namely papaverine, promethazine and propafenone the experimental equilibrium solubility data precisely follow the theoretical HH curve until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. It is critical that the pKa value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs.",
keywords = "Henderson-Hasselbaich relationship, Intrinsic solubility, Ionizable drugs, pH-dependent solubility, Shake-flask method",
author = "Gergely V{\"o}lgyt and Edit Baka and M{\'a}rta Kov{\'a}cs and K. Tak{\'a}cs-Nov{\'a}k",
year = "2011",
language = "Hungarian",
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T1 - Az egysúlyi oldhatóság meghatározá sának helyes gyakorlata II. Ionizálható vegyületek pH-függo{combining double acute accent} oldhatóságának vizsgálata

AU - Völgyt, Gergely

AU - Baka, Edit

AU - Kovács, Márta

AU - Takács-Novák, K.

PY - 2011

Y1 - 2011

N2 - In this paper the pH-equilibrium solubility profiles of ionizable drugs are presented. The aim of the present work was to study the validity of the Henderson-Hasselbaich (HH) relationship in the case of structurally diverse weak bases. In the case of monoprotic bases, namely papaverine, promethazine and propafenone the experimental equilibrium solubility data precisely follow the theoretical HH curve until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. It is critical that the pKa value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs.

AB - In this paper the pH-equilibrium solubility profiles of ionizable drugs are presented. The aim of the present work was to study the validity of the Henderson-Hasselbaich (HH) relationship in the case of structurally diverse weak bases. In the case of monoprotic bases, namely papaverine, promethazine and propafenone the experimental equilibrium solubility data precisely follow the theoretical HH curve until the limit of salt solubility. The common ion effect on salt solubility was found to be significant at low pHs. Deviation from the HH equation in the case of dibasic quetiapine hydrogen fumarate can be easily interpreted with the formation of different salt compositions. The significance of pH control and the effect of the salt form (e.g., fumarate) was also investigated. It is critical that the pKa value and the intrinsic solubility are accurately determined when the HH relationship is used to predict the pH-dependent aqueous solubility of drugs.

KW - Henderson-Hasselbaich relationship

KW - Intrinsic solubility

KW - Ionizable drugs

KW - pH-dependent solubility

KW - Shake-flask method

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