Inhibition of albendazole crystallization in poly(vinylpyrrolidone) solid molecular dispersions.
The main aim of the study was to investigate the mechanisms of the stabilizing effect of poly(vinylpyrrolidone) (PVP) on amorphous albendazole (ABZ). Solid dispersions of ABZ with PVP polymers and with a copolymer containing poly(vinylacetate) (PVP/VA) were prepared using the solvent casting method. The effects of PVP molecular weight, composition and content on the crystallization of ABZ from the amorphous state were investigated using differential scanning calorimetry. Stability of the amorphous drug with respect to isothermal crystallization was studied at different polymer concentrations and storage temperatures. Solid dispersions were found to be X-ray amorphous and exhibited a single glass transition temperature (Tg). Onset of crystallization and extent of inhibition increased with concentration and molecular weight of the homopolymer. In spite of its having a higher molecular weight, replacement of about 40% of vinylpyrrolidone monomers with vinylacetate groups (as in the copolymer) resulted in reduced inhibition of crystallization. ABZ crystallized from the amorphous state in the absence of polymer even when stored below the Tg. The solvent casting method greatly reduced the requirement for polymer to achieve X-ray amorphous solid dispersions. Such dispersions exhibited a significant increase in induction time and reduction in the rate of crystallization at polymer concentrations as low as 5% and at temperatures as high as 70 degrees C. Factors other than mobility, such as drug-polymer hydrogen bonding' were also found to be involved in crystallization inhibition.
Kalaiselvan
R
R
Department of Pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India. kalaipharmacy@yahoo.com
Mohanta
G P
GP
Manna
P K
PK
Manavalan
R
R
D015766:Albendazole / Q000737:chemistry*; D000871:Anthelmintics / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D010592:Pharmaceutic Aids; D011205:Povidone; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry
D000871:Anthelmintics; D010592:Pharmaceutic Aids; D015766:Albendazole; D011205:Povidone