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Caron, V., Hu, Y., Tajber, L., Erxleben, A., Corrigan, O.I., McArdle, P, Healy, A.M.
2013
March
Aaps Pharmscitech
Amorphous solid dispersions of sulfonamide/soluplus (R) and sulfonamide/PVP prepared by ball milling
Published
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amorphous dispersions milling polyvinylpyrrolidone Soluplus sulphonamide SPRAY-DRIED COMPOSITES GLASS-TRANSITION SULFAMERAZINE POLYMORPHS STATE AMORPHIZATION MOLECULAR MOBILITY POWDER DIFFRACTION CRYSTALLIZATION PHARMACEUTICALS INDOMETHACIN SYSTEMS
14
464
474
The aim of this paper is to investigate the physicochemical properties of binary amorphous dispersions of poorly soluble sulfonamide/polymeric excipient prepared by ball milling. The sulfonamides selected were sulfathiazole (STZ), sulfadimidine (SDM), sulfamerazine (SMZ) and sulfadiazine (SDZ). The excipients were polyvinylpyrrolidone (PVP) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer, commercially known as Soluplus (R). Co-milled systems were characterised by powder X-ray diffraction and differential scanning calorimetry. PVP was shown to form amorphous dispersions over a wider composition range than Soluplus (R) for the four sulfonamides tested. Moreover, amorphous dispersions made with PVP were homogeneous [single glass transition (Tg)], while amorphous dispersions made from Soluplus (R) were heterogeneous (two Tgs). This behaviour is consistent with the fact that all the sulfonamides tested presented a lower solubility in Soluplus (R) than in PVP, as evidenced by Flory-Huggins parameters determined. Amorphous dispersions of SDM with Soluplus (R) could be produced even though SDM does not amorphise alone upon milling and Soluplus (R) presents Tg at a lower temperature than SDM. Amorphous dispersions of SMZ could be prepared with a lower excipient concentration compared to STZ, SDM and SDZ, which may reflect the one-dimensional H-bonding network in SMZ compared to the 2D or 3D H-bonding network found in the other sulfonamides. Stability tests (60% RH/25 degrees C) revealed that dispersions made with Soluplus (R) remained dry and powdery compared to those made with PVP that formed a sticky paste in less than 2 weeks, indicating a possible advantage of using Soluplus (R) in terms of increased physical stability under high humidity storage conditions.
DOI 10.1208/s12249-013-9931-7
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