pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides
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Amphiphilic tricyclic bases are surface-active, sparingly-soluble drugs, which can exhibit
complicated aqueous solution chemistry. New pH-Ramp Shake-Flask method was
previously applied to desipramine hydrochloride solubility studies and described in the
literature [1]. Solubility was measured using state-of-the-art experimental design,
recommended in the white paper on equilibrium solubility measurements [2]. The aim of
this study was to examine solubility-pH behavior of desipramine structural analogues:
imipramine and amitriptyline hydrochlorides (Figure 1). Imipramine and amitriptyline are
tricyclic antidepressants, which are used in the treatment of mental illnesses. pH-Ramp
Shake-Flask method was applied. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow
sedimentation, and oil forms make solubility determination extremely challenging. Oils
which are more soluble than crystalline forms are formed in alkaline solutions (above pH...
7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be
unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult,
especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis
detection. Different techniques were used for solid phase characterization. Solid phase
characterization is particularly important in complicated systems like this.
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8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019, 2019, 51-51Publisher:
- International Association of Physical Chemists
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-MESTD-Basic Research (BR or ON)-172008)
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
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Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Marković, Olivera S. AU - Pešić, Miloš P. AU - Avdeef, Alex AU - Verbić, Tatjana PY - 2019 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5942 AB - Amphiphilic tricyclic bases are surface-active, sparingly-soluble drugs, which can exhibit complicated aqueous solution chemistry. New pH-Ramp Shake-Flask method was previously applied to desipramine hydrochloride solubility studies and described in the literature [1]. Solubility was measured using state-of-the-art experimental design, recommended in the white paper on equilibrium solubility measurements [2]. The aim of this study was to examine solubility-pH behavior of desipramine structural analogues: imipramine and amitriptyline hydrochlorides (Figure 1). Imipramine and amitriptyline are tricyclic antidepressants, which are used in the treatment of mental illnesses. pH-Ramp Shake-Flask method was applied. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult, especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis detection. Different techniques were used for solid phase characterization. Solid phase characterization is particularly important in complicated systems like this. PB - International Association of Physical Chemists C3 - 8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019 T1 - pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides SP - 51 EP - 51 UR - https://hdl.handle.net/21.15107/rcub_cherry_5942 ER -
@conference{ author = "Marković, Olivera S. and Pešić, Miloš P. and Avdeef, Alex and Verbić, Tatjana", year = "2019", abstract = "Amphiphilic tricyclic bases are surface-active, sparingly-soluble drugs, which can exhibit complicated aqueous solution chemistry. New pH-Ramp Shake-Flask method was previously applied to desipramine hydrochloride solubility studies and described in the literature [1]. Solubility was measured using state-of-the-art experimental design, recommended in the white paper on equilibrium solubility measurements [2]. The aim of this study was to examine solubility-pH behavior of desipramine structural analogues: imipramine and amitriptyline hydrochlorides (Figure 1). Imipramine and amitriptyline are tricyclic antidepressants, which are used in the treatment of mental illnesses. pH-Ramp Shake-Flask method was applied. Appearance of aggregates (trimer, around pH 4 in imipramine case), which lead to slow sedimentation, and oil forms make solubility determination extremely challenging. Oils which are more soluble than crystalline forms are formed in alkaline solutions (above pH 7.8 in imipramine case). Sometimes in such cases, pH adjustment in that pH region can be unpredictable. Furthermore, oil sticks to electrode making pH measurement difficult, especially in amitryptiline case. Concentration was measured using HPLC with UV/Vis detection. Different techniques were used for solid phase characterization. Solid phase characterization is particularly important in complicated systems like this.", publisher = "International Association of Physical Chemists", journal = "8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019", title = "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides", pages = "51-51", url = "https://hdl.handle.net/21.15107/rcub_cherry_5942" }
Marković, O. S., Pešić, M. P., Avdeef, A.,& Verbić, T.. (2019). pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019 International Association of Physical Chemists., 51-51. https://hdl.handle.net/21.15107/rcub_cherry_5942
Marković OS, Pešić MP, Avdeef A, Verbić T. pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides. in 8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019. 2019;:51-51. https://hdl.handle.net/21.15107/rcub_cherry_5942 .
Marković, Olivera S., Pešić, Miloš P., Avdeef, Alex, Verbić, Tatjana, "pH-Dependent solubility profiles of imipramine and amitriptyline hydrochlorides" in 8th IAPC Meeting Eighth World Conference on Physico-Chemical Methods in Drug Discovery & Fifth World Conference on ADMET and DMPK , Split, Croatia, September 9-11, 2019 (2019):51-51, https://hdl.handle.net/21.15107/rcub_cherry_5942 .