Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability

Abstract

We have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin-polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally diverse set of amorphous dispersion polymers was investigated; poly(vinylpyrrolidone), Eudragit E100, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose (HPMC) and HPMC-acetate succinate. Mid-infrared spectroscopy was used to determine and quantify the extent of curcumin-polymer interactions. Physical stability under different environmental conditions was monitored by powder X-ray diffraction. Curcumin chemical stability was monitored by UV-Vis spectroscopy. Isolation of stable amorphous curcumin was difficult in the absence of polymers. Polymers proved to be effective curcumin crystallization inhibitors enabling the production of amorphous solid dispersions; however, the polymers showed very different abilities to inhibit crystallization during long-term storage. Curcumin intramolecular hydrogen bonding reduced the extent of its hydrogen bonding with polymers; hence most polymers were not highly effective crystallization inhibitors. Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.

Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

“…It was found that only by creating strong hydrogen bonds between resveratrol and the polymer could crystallization inhibition be achieved . However, for curcumin, where all hydrogen‐bond donors are involved in intramolecular hydrogen bonds, it was found to be difficult to stabilize the amorphous solid dispersion with only hydrogen‐bond interactions as these interactions were not as energetically favourable as the curcumin intramolecular interaction . For the naringenin and quercetin polyphenols investigated in this study there are hydrogen‐bond donors involved in intramolecular interactions as well as hydrogen‐bond donors only involved in intermolecular interactions; therefore, it is expected that some stabilization against crystallization will occur through the formation of polyphenol–polymer hydrogen‐bond interactions.…”

“…The lack of hydrogen bonding can explained by the ionization of the dimethylamino group when a polyphenol is present; therefore, the dimethylamino group of the E100 polymer did not form strong hydrogen bonds with the polyphenols as it was no longer available for hydrogen bonding due to the ionic interaction. This ionic interaction is much stronger than hydrogen bonding and has also been observed in amorphous solid dispersions of E100 and the polyphenols resveratrol and curcumin . These polyphenols had increased physical stability due to the ionic interaction with E100, thus it is unsurprising that this interaction is also seen with naringenin and quercetin and leads to increased long‐term physical stability.…”

“…Considering the structure and hydrogen‐bonding scheme in the flavonoids, it is reasonable to expect that polymers that can provide better hydrogen bonding or energetically favourable interactions other than the flavonoid–flavonoid interactions will be good crystallization inhibitors. Recent studies on two other flavonoids, resveratrol and curcumin, have suggested that polyphenol–polymer hydrogen bonding is very important for crystallization inhibition. Resveratrol has a very high melting point and is classified as a rapid crystallizer according to the classification system of Van Eerdenbrugh et al .…”

“…Recent studies from our group have suggested correlations between the extent to which different polymers form drug–polymer intermolecular interactions and their ability to inhibit crystallization . Furthermore, studies with resveratrol and curcumin suggest that infrared (IR) spectroscopy is a useful method for monitoring drug–polymer interactions in order to predict amorphous solid dispersion stability against crystallization . The objective of the current study is to further explore the utility of this IR‐based approach for the rational selection of polymers that are effective crystallization inhibitors.…”

Enhanced antitumor efficacy of folate targeted nanoparticles co-loaded with docetaxel and curcumin

“…It has been reported CU have anticancer activity through suppressing the proliferation of tumor cells [4,5]. However, the clinical application of it has been highly restricted due to its low bioavailability, which results from its low aqueous solubility (11 ng/mL at pH 5.0) [6].…”