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Sci. Pharm. 2011, 79(3), 479-492; doi:10.3797/scipharm.1105-04

Preformulation Studies of Zidovudine Derivatives: Acid Dissociation Constants, Differential Scanning Calorimetry, Thermogravimetry, X-Ray Powder Diffractometry and Aqueous Stability Studies

Departamento de Farmacia, Facultad de Ciencias Químicas, Ciudad Universitaria, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina
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Received: 2 May 2011 / Accepted: 25 July 2011 / Published: 25 July 2011
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Abstract

As part as of the preformulation studies of new 5'-OH derivatives of zidovudine, compounds 2–6, their acid dissociation constants, Differential Scanning Calorimetry (DSC) and Thermogravimetry (TG) curves, X-Ray Powder diffractograms and aqueous stability are reported. A sensitive technique such as differential scanning potentiometry was used to determine the pKa constants of the above mentioned compounds. In addition, pKa values were calculated from theoretical methods, and no significant differences with those of experimental ones were observed. X-Ray Powder Diffractometry data demonstrated that compounds 2–4 were crystalline while 5 and 6 were amorphous. DSC analysis indicated that all of them presented an exothermic decomposition peak above 150 °C which is accompanied by a weight loss in the respective TG curves. The stability of these compounds in aqueous medium at different pH values was investigated, using a validated High Performance Liquid Chromatography (HPLC) method, which demonstrated to be rapid, selective, sensitive, accurate and stability-indicating. Good recovery, linearity and precision were also achieved. For all compounds the aqueous hydrolysis followed a pseudo-first-order kinetics, depending on pH and the union existing between AZT and the associate moiety. The hydrolysis was catalyzed by hydroxide ion in the 7.4–13.2 pH range, while all compounds exhibited pH-independent stability from acidic to neutral media (pHs 1.0–7.4).
Keywords: AZT derivatives; Acid dissociation constants; DSC and TG; X-Ray Powder Diffractometry; Aqueous stability AZT derivatives; Acid dissociation constants; DSC and TG; X-Ray Powder Diffractometry; Aqueous stability
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

RAVIOLO, M.A.; BRIÑÓN, M.C. Preformulation Studies of Zidovudine Derivatives: Acid Dissociation Constants, Differential Scanning Calorimetry, Thermogravimetry, X-Ray Powder Diffractometry and Aqueous Stability Studies. Sci. Pharm. 2011, 79, 479-492.

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