Effect of Polymer Additives on the Crystal Habit of Metformin HCl

Abstract

The crystal habit can have a profound influence on the physical properties of crystalline materials, and thus controlling the crystal morphology is of great practical relevance across many industries. Herein, this work investigates the effect of polymer additives on the crystal habit of metformin HCl with both experiments and computational methods with the aim of developing a combined screening approach for crystal morphology engineering. Crystallization experiments of metformin HCl are conducted in methanol and in an isopropanol-water mixture (8:2 V/V). Polyethylene glycol, polyvinylpyrrolidone, Tween80, and hydroxypropyl methylcellulose polymer additives are used in low concentrations (1-2% w/w) in the experiments to study the effect they have on modifying the crystal habit. Additionally, this work has developed computational methods to characterize the morphology "landscape" and quantifies the overall effect of solvent and additives on the predicted crystal habits. Further analysis of the molecular dynamics simulations is used to rationalize the effect of additives on specific crystal faces. This work demonstrates that the effects of additives on the crystal habit are a result of their absorption and interactions with the slow growing {100} and {020} faces.

Effect of Additives on the Morphology of γ-Aminobutyric Acid Crystals

“…They are commonly used drug excipients and do not raise any regulatory issues in pharmaceutical crystallization. 39 We found that HEC had a significant effect on the crystal morphology of GABA in the cooling crystallization, and other polymer additives did not display a strong influence. With the increase of HEC concentration, obvious change of GABA crystal morphology could be observed ( Figure 3 ).…”

“…Water-soluble polymer additives like polyvinylpyrrolidone, HEC, hydroxypropyl methyl cellulose, carboxymethyl cellulose, and methyl cellulose were studied. They are commonly used drug excipients and do not raise any regulatory issues in pharmaceutical crystallization . We found that HEC had a significant effect on the crystal morphology of GABA in the cooling crystallization, and other polymer additives did not display a strong influence.…”

Crystal growth and morphology control of needle-shaped organic crystals

“…99 The needle shape of metformin hydrochloride crystals is improved in the presence of PVP, PEG, Tween 80 or hydroxypropylmethyl cellulose (HPMC). 101,102 The morphology of nitrofurantoin crystals changed from needle-like to dendritic on addition of poly( N -isopropyl acrylamide) or hydroxypropylmethyl cellulose which was attributed to steric hindrance and H bonding (Fig. 12).…”

Herbal Medicine Nanocrystals: A Potential Novel Therapeutic Strategy

“…The morphology of nanocrystals varies based on the preparation methods or stabilizers employed. Stabilizers have been shown to influence crystal growth rates in distinct directions [48], yielding diverse morphologies, such as needle-like, spherical, flaky, cubic, and rod-like crystals. This phenomenon significantly impacts the dissolution and bioavailability of nanocrystals [11].…”