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LIU Juan, ZHENG Xueqin, CHENG Linfeng, ZHANG Ying, GAO Yuan, ZHANG Jianjun. Effect of polymers on the formation thermodynamics of adefovir dipifoxil-saccharin cocrystal[J]. Journal of China Pharmaceutical University, 2015, 46(2): 194-200. DOI: 10.11665/j.issn.1000-5048.20150210
Citation: LIU Juan, ZHENG Xueqin, CHENG Linfeng, ZHANG Ying, GAO Yuan, ZHANG Jianjun. Effect of polymers on the formation thermodynamics of adefovir dipifoxil-saccharin cocrystal[J]. Journal of China Pharmaceutical University, 2015, 46(2): 194-200. DOI: 10.11665/j.issn.1000-5048.20150210

Effect of polymers on the formation thermodynamics of adefovir dipifoxil-saccharin cocrystal

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  • The aim of this study was to investigate the effect of polymers on the formation thermodynamics of adefovir dipifoxil(AD)-saccharin(SAC)cocrystal. In the absence and presence of polymers such as polyethylene glycol, ethyl cellulose, polyvinylpyrrolidone and Eudragit E100, solubilities of AD and SAC in ethanol solution containing different concentrations of SAC at variable temperatures were determined by high-performance liquid chromatography(HPLC). Appropriate mathematical model for the description of the influence of polymers and temperature on the solubility of AD-SAC cocrystal was established. The ternary phase diagrams were set up using the assayed solubilities data, and they were used to predict changes of cocrystals solubility and product yield. Addition of polymers resulted in increased solubility of AD-SAC cocrystal, decreased complexation constants(K11), enhanced solubility products(Ksp), but there was a gradually decreased free energy change(ΔG0). The areas of homogeneous liquid phase and pure solid cocrystal in equilibrium with the liquid phase in ternary phase diagrams were also found to be larger. Therefore, although there was no change to the spontaneity of AD-SAC cocrystal formation, there existed retardation to cocrystal formation and reduction in product yield of pure cocrystal in the presence of polymers. Moreover, application of polymers could broaden the concentration range of AD and SAC solutions when solution crystallization was selected to prepare cocrystal.
  • [1]
    Miroshnyk I,Mirza S,Sandler N.Pharmaceutical co-crystals—an opportunity for drug product enhancement[J].Expert Opin Drug Deliv,2009,6(4):333-341.
    [2]
    Gao Y,Zu H,Zhang JJ.Pharmaceutical cocrystals[J].Prog Chem(化学进展),2010,22(5):829-836.
    [3]
    Starrett JE,Tortolani DR,Russell J,et al.Synthesis,oral bioavailability determination,and in vitro evaluation of prodrugs of the antiviral agent 9-[2-(phosphonomethoxy)ethyl]adenine(PMEA)[J].J Med Chem,1994,37(12):1857-1864.
    [4]
    Gao Y,Zu H,Zhang JJ.Enhanced dissolution and stability of adefovir dipivoxil by cocrystal formation[J].J Pharm Pharmacol,2011,63(4):483-490.
    [5]
    Gao Y,Gao J,Liu ZL,et al.Coformer selection based on degradation pathway of drugs:a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals[J].Int J Pharm,2012,438(1):327-335.
    [6]
    Ma K, Zhang Y, Kan HL, et al. Thermodynamic and kinetic investigation on the crucial factors affecting adefovir dipivoxil-saccharin cocrystallization[J].Pharm Res,2014,31(7):1766-1778.
    [7]
    Zhang JJ,Zu H,Gao Y.Formation thermodynamics of adefovir dipivoxil-saccharin co-crystals[J].Acta Phys Chim Sin(物理化学学报),2011,27(3):547-552.
    [8]
    Myerson A.Handbook of Industrial Crystallization[M].Boston:Butterworth-Heinemann,1993:65-87.
    [9]
    Lee MK,Lee H,Kim I,et al.Novel polymorphic form of adefovir dipivoxil derived from polymer-directed crystallization[J].Pharmazie,2011,66(10):766-770.
    [10]
    Jung S,Ha JM,Kim IW.Phase Transformation of adefovir dipivoxil/succinic acid cocrystals regulated by polymeric additives[J].Polymers,2013,6(1):1-11.
    [11]
    Nehm SJ,Rodríguez-Spong B,Rodríguez-Hornedo N.Phase solubility diagrams of cocrystals are explained by solubility product and solution complexation[J].Cryst Growth Des,2006,6(2):592-600.
    [12]
    Ilevbare GA,Liu H,Edgar KJ,et al.Understanding polymer properties important for crystal growth inhibition-impact of chemically diverse polymers on solution crystal growth of ritonavir[J].Cryst Growth Des,2012,12(6):3133-3143.
    [13]
    Zheng JM.Medical Polymer Materials(药用高分子材料学)[M].3rd ed.Beijing:Chinese Medical Science Press,2009:200-211
    [14]
    Schartman RR.On the thermodynamics of cocrystal formation[J].Int J Pharm,2009,365(1):77-80.
    [15]
    Ozaki S, Kushida I, Yamashita T, et al. Inhibition of crystal nucleation and growth by water-soluble polymers and its impact on the supersaturation profiles of amorphous drugs[J].J Pharm Sci,2013,102(7):2273-2281.
    [16]
    Xu S,Dai WG.Drug precipitation inhibitors in supersaturable formulations[J].Int J Pharm,2013,453(1):36-43.
    [17]
    Raghavan SL, Trividic A, Davis AF, et al. Crystallization of hydrocortisone acetate:influence of polymers[J].Int J Pharm,2001,212(2):213-221.
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