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Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints
dc.creator | Marković, Olivera | |
dc.creator | Patel, Nirali G. | |
dc.creator | Serajuddin, Abu T. M. | |
dc.creator | Avdeef, Alex | |
dc.creator | Verbić, Tatjana | |
dc.date.accessioned | 2022-02-08T10:49:54Z | |
dc.date.available | 2023-01-20 | |
dc.date.issued | 2022 | |
dc.identifier.issn | 1543-8384 | |
dc.identifier.uri | https://cer.ihtm.bg.ac.rs/handle/123456789/4936 | |
dc.description.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. | sr |
dc.language.iso | en | sr |
dc.publisher | American Chemical Society (ACS) | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200026/RS// | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/inst-2020/200168/RS// | sr |
dc.relation.isversionof | https://cer.ihtm.bg.ac.rs/handle/123456789/4934 | |
dc.relation.isversionof | https://doi.org/10.1021/acs.molpharmaceut.1c00919 | |
dc.relation.isreferencedby | https://cer.ihtm.bg.ac.rs/handle/123456789/4935 | |
dc.rights | embargoedAccess | sr |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | Molecular Pharmaceutics | sr |
dc.subject | nortriptyline | sr |
dc.subject | nortriptyline hydrochloride | sr |
dc.subject | phosphate salts | sr |
dc.subject | complexes | sr |
dc.subject | solubility | sr |
dc.subject | solubility product | sr |
dc.subject | pH and buffer effect | sr |
dc.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 | sr |
dc.type | article | sr |
dc.rights.license | BY-NC | sr |
dc.citation.volume | 19 | |
dc.citation.issue | 2 | |
dc.citation.spage | 710 | |
dc.citation.epage | 719 | |
dc.citation.rank | M21~ | |
dc.description.other | This is the peer-reviewed version of the article: Marković, Olivera S., Patel, Nirali G., Serajuddin, Abu T. M., Avdeef, Alex, Verbić, Tatjana Ž., "Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraints", Molecular Pharmaceutics, 19, no. 2 (2022):710-719, [https://doi.org/10.1021/acs.molpharmaceut.1c00919] | |
dc.description.other | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [https://doi.org/10.1021/acs.molpharmaceut.1c00919] | |
dc.description.other | The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/4934] | |
dc.description.other | Supporting information: [https://cer.ihtm.bg.ac.rs/handle/123456789/4935] | |
dc.identifier.pmid | 35050628 | |
dc.identifier.doi | 10.1021/acs.molpharmaceut.1c00919 | |
dc.identifier.fulltext | http://cer.ihtm.bg.ac.rs/bitstream/id/21366/acc-post-combined.pdf | |
dc.identifier.wos | 000746418500001 | |
dc.type.version | acceptedVersion | sr |