Microcrystallization of indomethacin using a pH-shift method

• Published in: International journal of pharmaceutics 2003-09, Vol.263 (1), p.141-150
• Main Authors: Kim, Sung Tae, Kwon, Jai-Hyun, Lee, Jae-Jeong, Kim, Chan-Wha
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cell Survival - drug effects; Cell Survival - physiology; Crystallization; Dose-Response Relationship, Drug; General aspects; HT-29; HT29 Cells; Humans; Hydrogen-Ion Concentration; Indomethacin; Indomethacin - chemical synthesis; Indomethacin - pharmacology; Medical sciences; Microcrystallization; pH-shift; Pharmacology. Drug treatments; Technology, Pharmaceutical - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(03)00358-2

This study developed a microcrystallization process for indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), using a pH-shift method in aqueous solution. The physicochemical properties of the microcrystals produced were similar to those of the standard crystalline powder in X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR) analyses, except for a lower XRD peak height and a slightly lower melting temperature ( T m) (1.5 °C). Phase contrast microscopy and scanning electron microscopy (SEM) showed that the indomethacin microcrystals were plate-like with a uniform size distribution (mean diameter=10.4±0.4 μm). In the initial phase, the dissolution rate of the indomethacin microcrystals was about 2.2 times higher than that of the standard crystalline powder. The biological activity of the indomethacin microcrystals was about 20% higher than that of the standard crystalline powder in their ability to inhibit the proliferation of colon cancer cells (HT-29).