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dc.creatorMarković, Olivera S.
dc.creatorPatel, Nirali G.
dc.creatorSerajuddin, Abu T. M.
dc.creatorAvdeef, Alex
dc.creatorVerbić, Tatjana
dc.date.accessioned2022-05-09T17:05:26Z
dc.date.available2023-02-07
dc.date.issued2022
dc.identifier.issn1543-8384
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/5039
dc.description.abstractThe 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.sr
dc.language.isoensr
dc.publisherAmerican Chemical Societysr
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200026/RS//sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/inst-2020/200168/RS//sr
dc.rightsembargoedAccesssr
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceMolecular pharmaceuticssr
dc.subjectnortriptylinesr
dc.subjectnortriptyline hydrochloridesr
dc.subjectphosphate saltssr
dc.subjectcomplexessr
dc.subjectsolubilitysr
dc.subjectsolubility productsr
dc.subjectpH and buffer effectsr
dc.titleNortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule “Soft” Constraintssr
dc.typearticlesr
dc.rights.licenseBY-NC-NDsr
dc.rights.holderAmerican Chemical Societysr
dc.citation.volume19
dc.citation.issue2
dc.citation.spage710
dc.citation.epage719
dc.identifier.wos000763597800030
dc.identifier.doi10.1021/acs.molpharmaceut.1c00919
dc.type.versionpublishedVersionsr
dc.identifier.scopus2-s2.0-85123926863


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