Direct imaging of the dissolution of salt forms of a carboxylic acid drug

Kofi Asare-Addo, Karl Walton, Adam Ward, Ana-Maria Totea, Sadaf Taheri, Maen Al Shafiee, Nihad Mawla, Antony Bondi, William Evans, Adeola Adebisi, Barbara Conway, Peter Timmins

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV-imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV-imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV-imaging IDR data.
Original languageEnglish
Pages (from-to)290-299
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume551
Issue number1-2
Early online date20 Sep 2018
DOIs
Publication statusPublished - 15 Nov 2018

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Carboxylic Acids
Salts
Gemfibrozil
Pharmaceutical Preparations
Solubility
Cyclohexylamines
Dosage Forms
Biological Availability
Capsules
Industry

Cite this

Asare-Addo, Kofi ; Walton, Karl ; Ward, Adam ; Totea, Ana-Maria ; Taheri, Sadaf ; Al Shafiee, Maen ; Mawla, Nihad ; Bondi, Antony ; Evans, William ; Adebisi, Adeola ; Conway, Barbara ; Timmins, Peter. / Direct imaging of the dissolution of salt forms of a carboxylic acid drug. In: International Journal of Pharmaceutics. 2018 ; Vol. 551, No. 1-2. pp. 290-299.
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Direct imaging of the dissolution of salt forms of a carboxylic acid drug. / Asare-Addo, Kofi; Walton, Karl; Ward, Adam; Totea, Ana-Maria; Taheri, Sadaf; Al Shafiee, Maen; Mawla, Nihad; Bondi, Antony; Evans, William; Adebisi, Adeola; Conway, Barbara; Timmins, Peter.

In: International Journal of Pharmaceutics, Vol. 551, No. 1-2, 15.11.2018, p. 290-299.

Research output: Contribution to journalArticle

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T1 - Direct imaging of the dissolution of salt forms of a carboxylic acid drug

AU - Asare-Addo, Kofi

AU - Walton, Karl

AU - Ward, Adam

AU - Totea, Ana-Maria

AU - Taheri, Sadaf

AU - Al Shafiee, Maen

AU - Mawla, Nihad

AU - Bondi, Antony

AU - Evans, William

AU - Adebisi, Adeola

AU - Conway, Barbara

AU - Timmins, Peter

PY - 2018/11/15

Y1 - 2018/11/15

N2 - The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV-imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV-imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV-imaging IDR data.

AB - The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV-imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV-imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV-imaging IDR data.

KW - Salts

KW - Gemfibrozil

KW - Intrinsic dissolution rate

KW - Focus variation

KW - Surface dissolution imaging

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JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

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