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Amorphous solid dispersions of sulfonamide/soluplus® and sulfonamide/pvp prepared by ball milling
Caron, Vincent; Hu, Yun; Tajber, Lidia; Erxleben, Andrea; Corrigan, Owen I.; McArdle, Patrick; Healy, Anne Marie
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.
Keyword(s): amorphous dispersions; milling; polyvinylpyrrolidone; soluplus; sulphonamide; spray-dried composites; glass-transition; sulfamerazine polymorphs; state amorphization; molecular mobility; powder diffraction; crystallization; pharmaceuticals; indomethacin; systems
Publication Date:
Type: Journal article
Peer-Reviewed: Unknown
Institution: NUI Galway
Publisher(s): American Association of Pharmaceutical Scientists (AAPS)
First Indexed: 2019-03-23 06:41:48 Last Updated: 2019-09-20 06:59:20