Polymorphs of the antiviral drug ganciclovir

Abstract

Ganciclovir (GCV; systematic name: 2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-1H-purin-6-one), CHNO, an antiviral drug for treating cytomegalovirus infections, has two known polymorphs (Forms I and II), but only the structure of the metastable Form II has been reported [Kawamura & Hirayama (2009). X-ray Struct. Anal. Online, 25, 51-52]. We describe a successful preparation of GCV Form I and its crystal structure. GCV is an achiral molecule in the sense that its individual conformers, which are generally chiral objects, undergo fast interconversion in the liquid state and cannot be isolated. In the crystalline state, GCV exists as two inversion-related conformers in Form I and as a single chiral conformer in Form II. This situation is similar to that observed for glycine, also an achiral molecule, whose α-polymorph contains two inversion-related conformers, while the γ-polymorph contains a single conformer that is chiral. The hydrogen bonds are exclusively intermolecular in Form I, but both inter- and intramolecular in Form II, which accounts for the different molecular conformations in the two polymorphs.

Are Myths and Preconceptions Preventing Us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis?

“…This required market withdrawal and subsequent re-formulation [ 10 ]. Among other drugs currently investigated for COVID-19 treatment, HIV protease inhibitor lopinavir exists in as many as ten polymorphic forms [ 11 ] the macrolide antibiotic azithromycin (Zithromax ® ) occurs as three polymorphs [ 12 , 13 ], and a final form of the malaria medication hydroxychloroquine monosulfate is reported to exist as two polymorphs [Among other antivirals (i.e., not considered for COVID-19 treatment), the guanine nucleoside ganciclovir [ 14 , 15 ], a commonly used antiviral for herpes simplex virus acyclovir [ 16 ], and the anti-hepatitis drug clevudine [ 17 ] are polymorphic.…”

Ionic Liquids as Tools to Incorporate Pharmaceutical Ingredients into Biopolymer-Based Drug Delivery Systems

“…Further, APIs can crystallize in the form of solvates and hydrates which can also have polymorphs with different solubilities [ 17 , 18 ] and bioavailabilities [ 19 , 20 ]. The classic example is Ganciclovir, an antiviral guanine nucleoside that has two polymorphic forms and two hydrates [ 21 , 22 ] significantly less water-soluble than its originally marketed form [ 23 ]. Another example is the accidental discovery of polymorph II of Ritonavir which resulted in its market withdrawal [ 24 ].…”