TY  - JOUR
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4936
AB  - The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,2019), was applied. An improved and more detailed experimentaldesign of the Nor solubility measurement allowed us to exploit thefull capacity of the pH-RSF method. Complex equilibria in theaqueous phase (cationic and anionic complex formation betweenNor and the phosphate) and solid-phase transformations (Nor freebase, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)were characterized by a detailed analysis of the solubilitymeasurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustratethe influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in theformulation of drug products.
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
VL  - 19
IS  - 2
SP  - 710
EP  - 719
DO  - 10.1021/acs.molpharmaceut.1c00919
ER  - 

@article{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,2019), was applied. An improved and more detailed experimentaldesign of the Nor solubility measurement allowed us to exploit thefull capacity of the pH-RSF method. Complex equilibria in theaqueous phase (cationic and anionic complex formation betweenNor and the phosphate) and solid-phase transformations (Nor freebase, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)were characterized by a detailed analysis of the solubilitymeasurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustratethe influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in theformulation of drug products.",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints",
volume = "19",
number = "2",
pages = "710-719",
doi = "10.1021/acs.molpharmaceut.1c00919"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics
American Chemical Society (ACS)., 19(2), 710-719.
https://doi.org/10.1021/acs.molpharmaceut.1c00919

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics. 2022;19(2):710-719.
doi:10.1021/acs.molpharmaceut.1c00919 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints" in Molecular Pharmaceutics, 19, no. 2 (2022):710-719,
https://doi.org/10.1021/acs.molpharmaceut.1c00919 . .

TY  - JOUR
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4934
AB  - The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
VL  - 19
IS  - 2
SP  - 710
EP  - 719
DO  - 10.1021/acs.molpharmaceut.1c00919
ER  - 

@article{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published “white paper” (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pHRSF) method, introduced in our earlier work (Marković et al.,
2019), was applied. An improved and more detailed experimental
design of the Nor solubility measurement allowed us to exploit the
full capacity of the pH-RSF method. Complex equilibria in the
aqueous phase (cationic and anionic complex formation between
Nor and the phosphate) and solid-phase transformations (Nor free
base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts)
were characterized by a detailed analysis of the solubility
measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis,
differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate
the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth,
on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the
formulation of drug products.",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints",
volume = "19",
number = "2",
pages = "710-719",
doi = "10.1021/acs.molpharmaceut.1c00919"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics
American Chemical Society (ACS)., 19(2), 710-719.
https://doi.org/10.1021/acs.molpharmaceut.1c00919

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints. in Molecular Pharmaceutics. 2022;19(2):710-719.
doi:10.1021/acs.molpharmaceut.1c00919 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints" in Molecular Pharmaceutics, 19, no. 2 (2022):710-719,
https://doi.org/10.1021/acs.molpharmaceut.1c00919 . .

TY  - DATA
AU  - Marković, Olivera
AU  - Patel, Nirali G.
AU  - Serajuddin, Abu T. M.
AU  - Avdeef, Alex
AU  - Verbić, Tatjana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4935
AB  - Additional experimental details; preparation of stock suspensions for low-to-high pH and high-to-low pH titrations; titration and solubility data for titration sets 1–11; elemental analysis data from titration sets 9, 3, 6, and 7; and HPLC UV/VIS analysis─sample chromatograms and calibration diagram
PB  - American Chemical Society (ACS)
T2  - Molecular Pharmaceutics
T1  - Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"
DO  - 10.1021/acs.molpharmaceut.1c00919.s001
ER  - 

@misc{
author = "Marković, Olivera and Patel, Nirali G. and Serajuddin, Abu T. M. and Avdeef, Alex and Verbić, Tatjana",
year = "2022",
abstract = "Additional experimental details; preparation of stock suspensions for low-to-high pH and high-to-low pH titrations; titration and solubility data for titration sets 1–11; elemental analysis data from titration sets 9, 3, 6, and 7; and HPLC UV/VIS analysis─sample chromatograms and calibration diagram",
publisher = "American Chemical Society (ACS)",
journal = "Molecular Pharmaceutics",
title = "Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"",
doi = "10.1021/acs.molpharmaceut.1c00919.s001"
}

Marković, O., Patel, N. G., Serajuddin, A. T. M., Avdeef, A.,& Verbić, T.. (2022). Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints". in Molecular Pharmaceutics
American Chemical Society (ACS)..
https://doi.org/10.1021/acs.molpharmaceut.1c00919.s001

Marković O, Patel NG, Serajuddin ATM, Avdeef A, Verbić T. Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints". in Molecular Pharmaceutics. 2022;.
doi:10.1021/acs.molpharmaceut.1c00919.s001 .

Marković, Olivera, Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana, "Supporting information for: "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints"" in Molecular Pharmaceutics (2022),
https://doi.org/10.1021/acs.molpharmaceut.1c00919.s001 . .