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dc.creatorMarković, Olivera
dc.creatorPešić, Miloš P.
dc.creatorShah, Ankita V.
dc.creatorSerajuddin, Abu T.M.
dc.creatorVerbić, Tatjana
dc.creatorAvdeef, Alex
dc.date.accessioned2020-01-17T06:47:19Z
dc.date.available2020-03-18
dc.date.issued2019
dc.identifier.issn0928-0987
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/3342
dc.description.abstractAlthough solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published “white paper” (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12 0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsH.Cl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8 9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.sr
dc.language.isoensr
dc.publisherElseviersr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172035/RS//sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//sr
dc.rightsembargoedAccesssr
dc.sourceEuropean Journal of Pharmaceutical Sciencessr
dc.subjectdesipramine-phosphate complexessr
dc.subjectpH effectsr
dc.subjectbuffer effectsr
dc.subjectsolubility productsr
dc.subjectpH-Ramp Shake-Flask methodsr
dc.subjectpDISOL-Xsr
dc.titleSolubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregatessr
dc.typearticlesr
dc.rights.licenseBY-NC-NDsr
dcterms.abstractСхах, Aнкита В.; Серајуддин, Aбу Т.М.; Пешић, Милош П.; Вербић, Татјана; Марковић, Оливера; Aвдееф, Aлеx;
dc.rights.holderElseviersr
dc.citation.volume133
dc.citation.spage264
dc.citation.epage274
dc.citation.rankM21~
dc.description.otherThis is the peer-reviewed version of the following article: Marković, O. S.; Pešić, M. P.; Shah, A. V.; Serajuddin, A. T. M.; Verbić, T. Ž.; Avdeef, A. Solubility-PH Profile of Desipramine Hydrochloride in Saline Phosphate Buffer: Enhanced Solubility Due to Drug-Buffer Aggregates. European Journal of Pharmaceutical Sciences 2019, 133, 264–274. [https://doi.org/10.1016/j.ejps.2019.03.014]
dc.description.otherThe published version: [http://cer.ihtm.bg.ac.rs/handle/123456789/3211]
dc.identifier.pmid30914359
dc.identifier.doi10.1016/j.ejps.2019.03.014
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs/bitstream/id/15887/solubility_phprofile_acc.pdf
dc.identifier.scopus2-s2.0-85064240235
dc.identifier.wos000465174500026
dc.type.versionacceptedVersionsr


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