Pharmaceutical relationships of three solid state forms of stavudine

The effect of temperature and moisture on the amorphous-to-crystalline transformation of stavudine

“…Polymorphic forms I, II and III (a hydrated form with a stavudine:water stoichiometry of 3:1) were also prepared for comparison with the amorphous solid. These crystalline solids were obtained from recrystallization of the stavudine raw material form ethanol, methanol and milli-Q water, respectively (Gandhi et al, 2000).…”

“…Perhaps the inconsistent pharmacokinetic parameters are related to the unique physicochemical properties of stavudine. Stavudine has two known monotropically related polymorphs, form I is the more stable least soluble (89 mg/ml) and form II is the metastable more soluble form (106 mg/ml) (Gandhi et al, 2000;Mirmehrabi et al, 2006a,b). A hydrated form with a stavudine:water stoichiometry of 3:1 (form III, solubility 90 mg/ml) and a few solvates has also been described (Gandhi et al, 2000;Radatus and Murthy, 2003).…”

“…Stavudine has two known monotropically related polymorphs, form I is the more stable least soluble (89 mg/ml) and form II is the metastable more soluble form (106 mg/ml) (Gandhi et al, 2000;Mirmehrabi et al, 2006a,b). A hydrated form with a stavudine:water stoichiometry of 3:1 (form III, solubility 90 mg/ml) and a few solvates has also been described (Gandhi et al, 2000;Radatus and Murthy, 2003). Stavudine is highly susceptible to chemical degradation by hydrolysis (Dunge et al, 2005;Kaul et al, 2005).…”

Crystal Forms of Anti-HIV Drugs: Role of Recrystallization

“…Harte et al and Guruskaya et al have reported the single crystal of Form I and Form II respectively (Harte et al, 1991as sited in Gandhi et al, 2000Guruskaya et al, 1991as sited in Gandhi et al, 2000. However, the production of pure Form I i.,s reported by Gandhi et al who have established the conditions of recrystallization governing the formation of this thermodynamically most stable form (Gandhi et al, 2000). The stavudine obtained during the synthesis process is recrystallized from hot organic solvents as the final step in the synthesis.…”

Desenvolvimento e validação de método por cromatografia líquida de alta eficiência para determinação simultânea das impurezas timina e timidina na matéria-prima estavudina

“…Em estudos de análise térmica, o aquecimento da estavudina, após a fusão, promoveu a decomposição do fármaco e formação da timina como produto principal. 4 Relatou-se também que a timina é o principal produto da degradação hidrolítica e oxidativa da estavudina. 5 A timidina pode ser considerada uma impureza de síntese uma vez que é descrita como sendo um precursor químico utilizado em diferentes rotas de síntese da estavudina.…”