The effect of temperature and moisture on the amorphous-to-crystalline transformation of stavudine.
Stavudine is a nucleoside reverse transcriptase inhibitor active against HIV, and is known to exist in two polymorphic forms designated as forms I and II, and a hydrate form III. An amorphous solid of stavudine was successfully prepared and characterized during this investigation. A comprehensive evaluation of the stability of this amorphous solid showed that the amorphous solid transforms to either form II (anhydrous) or form III (hydrate) when exposed to temperature, in the absence or presence of moisture, respectively. The amorphous-to-hydrate transformation occurred at relatively low RH (>32%) and led to the formation of crystal aggregates of the hydrated form. Steady state growth rate analyses also showed that the amorphous-to-crystalline transformation occurs at a greater rate in the presence of moisture, compared to the transformation at the same temperature in a dry environment. Crystal growth studies showed that it is possible to stabilize the amorphous solid of stavudine against crystal transformations in the absence of moisture by coating it with poly(methyl methacrylate). However, this polymer coating could not prevent crystal growth from the amorphous solid during exposure to moisture.
Strydom
Schalk
S
Unit for Drug Research and Development, Faculty of Health Sciences, North-West University, Potchefstroom 2520, South Africa.
Liebenberg
Wilna
W
Yu
Lian
L
de Villiers
Melgardt
M
D019380:Anti-HIV Agents / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D006813:Humidity; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D018119:Stavudine / Q000737:chemistry*; D013696:Temperature
D019380:Anti-HIV Agents; D005079:Excipients; D019904:Polymethyl Methacrylate; D018119:Stavudine