Abstract
The growth of acetaminophen polymorphic crystals and the solution-mediated phase transition from trihydrate to form II in agarose gel were investigated. The form II crystals grown in gels, presumably because of the agarose content, dissolved less rapidly at high temperatures and were more stable than in water. The trihydrate crystals in the gel were also expected to be stabilized by containing agarose, but in fact the fine morphology resulted in reduced stability. The solution-mediated phase transition from trihydrate to form II via form II seeding took longer in the gel because the gel slowed down the dissolution of the trihydrate by hindering the dispersion of the form II seeds and delayed the growth of form II by reducing the diffusion rate of the molecules dissolved from the trihydrate. Delays in solution-mediated phase transition and changes in stability for crystals grown in gels indicate the effectiveness of gels in controlling polymorphisms in pharmaceutical compounds.
Highlights
Published: 5 September 2021The ability of a chemical compound to have more than one crystalline form is known as polymorphism [1]
Polymorphic crystals of acetaminophen were prepared in agarose gels
Forms I and II grew with the incorporation of agarose fibers, improving the stability but not affecting the crystal morphology
Summary
Published: 5 September 2021The ability of a chemical compound to have more than one crystalline form is known as polymorphism [1]. Polymorph crystals are classified into the most thermodynamically stable phase (form) and unstable phases including metastable phases. Stable phases have a more stable formation and lower solubility than unstable phases [3,4]. Polymorphism has especially direct medical implications because the dissolution rates depend on the polymorph’s type. The bioavailability of the stable phase, because of its lower solubility, is lower than that of other metastable phases [5]. Metastable phases readily transform into a stable phase. Suppression of transitions from metastable to stable phases can facilitate the analysis and handling of the metastable phase and may change the current stance on the use of the metastable phase in drug development [6,7]
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