title: Comparison of Aqueous and 1-Octanol Solubility as well as Liquid-Liquid Distribution of Acyclovir Derivatives and Their Complexes with Hydroxypropyl-β-Cyclodextrin.
abstract: The aim of the presented work is the comparison of aqueous and 1-octanol solubilities of different acyclovir derivatives and their hydroxypropyl-β-cyclodextrin inclusion complexes. The solubility measurements were carried out at different temperatures over the range 25-45 °C using water, 1-octanol, water saturated with 1-octanol, 1-octanol saturated with water, buffered aqueous solutions (pH = 5.5 and 7.0) and buffered aqueous solutions containing cyclodextrin as solvents. The aqueous solubilities of the compounds are very low but may be enhanced by complexation with hydroxypropyl-β-cyclodextrin, especially if the acyclovir derivatives have aromatic groups which may be included in the cyclodextrin cavity. The values of 1-octanol-water partition coefficients of acyclovir derivatives, obtained using extraction experiments, showed a similar sequence as the solubility results in 1-octanol. Additionally, some molecular mechanics and molecular dynamic calculations were performed to determine optimized structures of acyclovir derivative complexes with β-cyclodextrin treated as a model.
authors: Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors: Małgorzata
authors: M
authors: Koźbiał
authors: Paweł
authors: P
authors: Gierycz
keywords: Acyclovir derivatives; Complexation; Cyclodextrin; Partition; Solubility
references: AAPS PharmSciTech. 2003;4(3):E45
references: 14621977
references: Int J Pharm. 2007 Feb 1;329(1-2):1-11
references: 17137734
references: Antiviral Res. 2006 Sep;71(2-3):134-40
references: 16780965
references: Acta Pharm Nord. 1989;1(4):185-94
references: 2590460
references: Bioorg Med Chem. 2005 Mar 15;13(6):2089-96
references: 15727862
references: J Med Chem. 2002 Nov 7;45(23):5052-7
references: 12408716
references: J Med Chem. 2001 Nov 22;44(24):4284-7
references: 11708929
references: J Med Chem. 1984 Nov;27(11):1486-92
references: 6092636
references: Acta Crystallogr C. 2001 Jun;57(Pt 6):767-9
references: 11408700
references: Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):911-4
references: 14565309
references: Bioorg Med Chem. 2006 May 15;14(10):3535-42
references: 16458009
references: J Med Chem. 1991 Aug;34(8):2380-3
references: 1652016
references: J Pharm Sci. 2002 Dec;91(12):2593-8
references: 12434403
references: J Med Chem. 1994 Sep 16;37(19):3187-90
references: 7932543