Role of Mechanochemistry in Solid Form Selection and Identification of the Drug Praziquantel

Abstract

Identification of all possible polymorphs for a pharmaceutical compound is vital for the better formulation of medicine with desired properties. This study demonstrates the application of a mechanochemical approach to reveal new polymorphs of a drug and the potential of variable amounts of solvent in liquid-assisted grinding for solid form screening. Without solvent and by varying the amount of solvent added, we found two new polymorphs and an amorphous form, which were not reported previously. The finding portrays the advantage of the mechanochemical approach as a means of the polymorph screening strategy. While the focus here was on praziquantel, a similar approach is applicable to other pharmaceutical systems. This study also contributed to reinvestigate the solid-state behavior of the chiral praziquantel system, including the melt phase diagram and the role of experimental conditions on its phase behavior.

The origin of delayed polymorphism in molecular crystals under mechanochemical conditions

“…the ability of a molecule to crystallize in different packing arrangements) has proved to be a powerful probe for such investigations. 31,[35][36][37][38] Polymorphic crystalline forms typically differ only slightly in energy (ca. < 5 kJ.mol -1 ) 39 , and their interconversions occur with only small changes in the environmental conditions.…”

Quantitative reversible one pot interconversion of three crystalline polymorphs by ball mill grinding

“…liquid) acts to stabilize these surfaces, 25,34,35 thereby altering the relative stability of nanocrystals, and therefore with the potential to cause a polymorph conversion. 22,25 These fundamental concepts are universal and apply to all chemistries.…”

“…In most cases only two polymorphs have been prepared by ball mill grinding. 17,18 Only a handful of examples of the full or partial preparation of three polymorphic forms of the same substance (crystalline or amorphous) by ball mill grinding have been published to date: anthranilic acid, 19 γ-aminobutyric acid (GABA), 20 N-acetyl-L-phenylalanylamino, 21 praziquantel, 22 1 : 1 caffeine-anthranilic acid cocrystal, 23 and 1 : 1 salt of vinpocetine oxalate. 24 Polymorph conversion by ball mill grinding has been an area of interest, as it enables the formation of bulk quantities of metastable polymorphs by alternative techniques to traditional ones, 19 though often not accessible by classical solution methods.…”

“…24 Polymorph conversion by ball mill grinding has been an area of interest, as it enables the formation of bulk quantities of metastable polymorphs by alternative techniques to traditional ones, 19 though often not accessible by classical solution methods. [20][21][22] Recently, Arhangelskis et al demonstrated reversibility between two crystalline and one amorphous form of the 1 : 1 salt of vinpocetine oxalate. 24 Only partial reversibility of polymorph transformation between pairs of polymorphs has been shown in those cases where three crystalline polymorphs were obtained by ball mill grinding.…”

Sustainable solid form screening: mechanochemical control over nucleobase hydrogen-bonded organic framework polymorphism

“…17 Importantly, mechanochemistry makes products inaccessible from solution or challenging to isolate and is known for its efficiency in solid form [18][19][20][21][22][23][24][25][26][27][28][29] and polymorph screening. [30][31][32][33][34][35] DAP (Fig. 1), sometimes referred to as 2-aminoadenine, is important to many areas of science.…”