Influence of Soluplus on Solid-State Properties and Physical Stability of Indomethacin-Saccharin Co-crystal Formation Prepared by Air-Drying Process
- 261 Downloads
The effect of Soluplus on the solid-state characteristics and physical transformation of indomethacin (IMC), saccharin (SAC), IMC-SAC physical mixture, and the previously prepared IMC-SAC co-crystal was investigated after solvent evaporation via air-drying process.
Soluplus with γ-IMC or SAC (weight ratio = 1:1) was respectively prepared by completely dissolving both components in acetone by ultrasonication, and then evaporated via air-drying process. Soluplus was fully co-dissolved with the previously prepared IMC-SAC co-crystal (procedure I) or completely dissolved together with IMC-SAC physical mixture (procedure II) in acetone by ultrasonication, and then evaporated through air-drying process. The physical stability of both Soluplus/IMC-SAC systems was also carried out under accelerated storage conditions. All the samples were determined by thermoanalytical and FTIR spectroscopic studies with spectral curve-fitting technique.
Soluplus caused the amorphous formation of IMC or SAC in the Soluplus solid dispersion, in which the intermolecular hydrogen bonding interaction between SAC and Soluplus occurred. Although Soluplus did not influence the co-crystal formation between IMC and SAC in the solid dispersion, the polymorphic transformation and physical stability of Soluplus/IMC-SAC solid dispersion were markedly influenced by procedures I and II after evaporation via air-drying process.
Soluplus influences the amorphous or crystalline IMC-SAC co-crystal formulated in the solid dispersion prepared by procedure I or II via air-drying process. The amorphous IMC-SAC co-crystal in the Soluplus solid dispersion prepared by procedure I gradually transformed to a crystalline IMC-SAC co-crystal after storage at 40 ± 2 °C/75 ± 5 % RH conditions for 28 days, whereas the crystalline IMC-SAC co-crystal in the Soluplus solid dispersion prepared by procedure II via air-drying process maintained a long-term storage stability.
KeywordsSoluplus Indomethacin (IMC) Saccharin (SAC) Solid dispersion Co-crystal Stability Amorphous Crystalline Storage
This work was supported by Ministry of Science and Technology, Taipei, Taiwan, ROC (MOST 103-2320-B-264-002-MY2).
Compliance with Ethical Standards
Conflict of Interest
The authors declare no competing financial interest.
- 9.Ghadi R, Ghuge A, Ghumre S, Waghmare N, Kadam DVJ. Co-crystals: emerging approach in pharmaceutical design. Indo Am J Pharm Res. 2014;4:3881–93.Google Scholar
- 10.US FDA. Regulatory classification of pharmaceutical co-crystals, 2013.Google Scholar
- 17.Bevernage J, Forier T, Brouwers J, Tack J, Annaert P, Augustijns P. Excipient-mediated supersaturation stabilization in human intestinal fluids. Mol. Pharm. 2011;8564-70.Google Scholar
- 20.Surwase SA, Itkonen L, Aaltonen J, Saville D, Rades T, Peltonen L, Strachan CJ. Polymer incorporation method affects the physical stability of amorphous indomethacin in aqueous suspension. Eur J Pharm Biopharm. 2015.Google Scholar
- 30.Reintjes T. Solubility enhancement with BASF pharma polymers: solubilizer compendium. Germany: BASF SE Pharma Ingredients & Services; 2011.Google Scholar
- 35.Kao CY, Huang HH, Huang YT, Lin LH, Lin SY. Thermoanalytical and spectroscopic studies on amorphization and phase transition of amorphous indomethacin prepared by two melt-cooling processes. ScienceJet. 2015;4:148.Google Scholar
- 41.Nanjwade VK, Manvi FV, Ali SM, Nanjwade BK, Maste MM. New trend in the cocrystallization of active pharmaceutical ingredient. J Appl Pharm Sci. 2011;8:1–5.Google Scholar