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Updated: Nov 15, 2025

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
Indomethacin co-amorphous drug-drug systems with improved solubility, supersaturation, dissolution rate and physical
Hanan Fael1, A Levent Demirel1
1Department of Chemistry, Koç University, Istanbul, Turkey.
Abstract:
In this study, new co-amorphous drug systems were designed using a pharmacologically relevant combination to improve the solubility and dissolution of indomethacin. Combinations of indomethacin-paracetamol (IND-PAR) as an anti-inflammatory/pain killer, and indomethacin-nicotinamide (IND-NCT) for prevention of gastric ulcers caused by IND, were developed for co-amorphization. The effect of PAR and NCT on the solubility, supersaturation, and dissolution of the poorly soluble counterpart, IND, was investigated. PAR and NCT were found to enhance the solubility and supersaturation of IND in biorelevant medium (FaSSIF) and in FaSSIF blank. Differential scanning calorimetry (DSC) showed capability of IND-PAR and IND-NCT binary mixtures to form eutectic mixture. Powder X-ray diffraction and DSC indicated the formation of a homogenous co-amorphous system with single Tg value. Hydrogen bonding between IND and each of PAR and NCT were found to stabilize the co-amorphous systems as supported by FTIR studies. The intrinsic dissolution rate under sink conditions was improved over that of plain amorphous IND both in FaSSIF and FaSSIF blank. IND-PAR 2:1 and IND-NCT 1:1 were extremely stable and remained amorphous for 7 months at 25 °C, while all co-amorphous formulations were stable at least up to one month at 40 °C under dry condition. The present work demonstrates an improved approach to combine IND-PAR and IND-NCT as promising co-amorphous systems for potential therapeutical applications.
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