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

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).

Zidovudine-Poly(l-Lactic Acid) Solid Dispersions with Improved Intestinal Permeability Prepared by Supercritical Antisolvent Process

“…Results obtained in this are in close agreement with those described in the literature . Hence, results from both the XRD and DSC analyses of the L3, L5, and L9 SD systems strongly suggest that AZT is in crystalline form in those systems.…”

Poly(ethylene glycol) enclatherated pectin-mucin submicron matrices for intravaginal anti-HIV-1 drug delivery

“…AZT was shown to be crystalline by several sharp peaks that include major peaks at 2θ equal to 9.000º, 14.891, 15.725º, 16.040º, 17.304º, 21.41º, 21.640º, 24.513º, 27.140º, 28.050º and 29.500º observed on its diffractogram shown in Fig. 8d which are similar to the ones previously reported by Raviolo and Briñón (Raviolo and Briñón, 2011). The observed patten in the diffractograms in Fig.…”

“…The XRD diffractograms generated were used to evaluate the crystallinity of the respective samples Mishra et al, 2008;Kumar et al, 2010;Raviolo and Briñón, 2011).…”

Ozonation products of zidovudine and thymidine in oxidative water treatment

“…Second order rate constants of ZDV ranged from 2.79 ∙ 10 4 M −1 s −1 at pH 7 up to 3.18 ∙ 10 4 M −1 s −1 at pH 3, corresponding to half-lives from 21 to 24 s at concentration levels of 1.5 μM, respectively ( Table 2 ). The absence of a pH dependence is expected considering pKa values of 9.45 for THY, as well as 9.42 for ZDV ( Raviolo and Brinon 2011 ). Similar kinetics in the absence of t -BuOH indicate that contribution of hydroxyl radicals to ZDV and THY degradation is negligible.…”