Polymorphic and pseudomorphic transformation behavior of acyclovir based on thermodynamics and crystallography

Solvent driven phase transitions of acyclovir – the role of water and solvent polarity

“…This observation was attributed to similar arrangements of the purine rings in the crystal structures of forms I and VI, and the substantial difference in the ring arrangement between the forms I and V. Furthermore, Terada et al hypothesized that anhydrous forms I and II do not undergo direct reciprocal transformation due to different arrangements of the purine rings in both crystal structures. 5 In this manuscript we show that ACV form I undergoes transformation to ACV form II in anhydrous methanol, ethanol, N,N-dimethylformamide and dimethylsulfoxide. To the best of our knowledge, very little is known about solvent induced phase transitions of ACV.…”

“…The reported crystalline phases were obtained using polymer-induced heteronucleation (PIHn) and at increased temperatures by Lutker et al 4 and through the application of dynamic vapour sorption by Terada et al ( Figure 1B, ESI Figure S11). 5 Based on the studies of Lutker et al 4 and Terada et al 5 ACV forms two hydrates -the commercially available 3:2 ACV:water hydrate (form V) and a 1:2 dihydrate (form VI), two anhydrous forms, I and II, and two forms stable only at high temperature, forms III and IV. 4 ACV form V was first reported by Birnbaum et al in 1980s.…”

“…The second anhydrous form, ACV form II, can be obtained via solution crystallisation of the commercial form of acyclovir in methanol at 68 °C in a closed vial followed by evaporating the solvent under continuous heating 4 or by precipitation from NNDMF using acetonitrile as antisolvent. 5 Dynamic vapor sorption studies carried out by Terada et al have shown that above 90% RH form I transforms into dihydrate (form VI), while form II transforms to 3:2 hydrate (form V) above 95% RH. 5 The metastable anhydrous form III can be obtained by heating the commercial form V between 130 and 150 °C and rapidly returns to the form V during cooling upon exposure to atmospheric water.…”

“…5 Dynamic vapor sorption studies carried out by Terada et al have shown that above 90% RH form I transforms into dihydrate (form VI), while form II transforms to 3:2 hydrate (form V) above 95% RH. 5 The metastable anhydrous form III can be obtained by heating the commercial form V between 130 and 150 °C and rapidly returns to the form V during cooling upon exposure to atmospheric water. Further heating of the metastable form III to 180 °C leads to the formation of the high-temperature stable form IV, which after cooling to room temperature undergoes a phase change to form I, which is stable at room temperature.…”

Drug delivery approaches of an antiviral drug: A comprehensive review

“…The drawbacks observed in the physicochemical and pharmacokinetic properties of this guanine derivative such as slight water solubility (1.3 mg/mL at 25°C), poor permeability (0.12 × 10 −6 -2.0 × 10 −6 cm / s), short half-life (2.5-3.3 h) and poor oral bioavailability (10-20%) have attracted the attention of many researchers to make efforts in designing modified novel dosage forms, ultimately aiming to achieve 100% success in its therapy. Since the physicochemical characteristics of an active pharmaceutical ingredient (API) are the exclusive criteria responsible for its stability, solubility and permeability, certain scientists have worked on these properties of ACV such as ionization, [1] structural and electronic properties, [2] polymorphism and pseudopolymorphism, [3][4][5] compatibility study with excipient, [6] which ultimately helped in the suitable modifications for the dosage form designing. This paper is a review that focuses on different research works, especially aimed on the modification and development of ACV drug therapy by applying modern techniques as shown in Figure 1, to enhance the bioavailability and therapeutic efficacy of the drug.…”