Stabilization of amorphous indomethacin by co-grinding in a ternary mixture

• Published in: International journal of pharmaceutics Vol. 241; no. 1; pp. 103 - 111
• Main Authors: Watanabe, Tomoyuki, Ohno, Ikumasa, Wakiyama, Naoki, Kusai, Akira, Senna, Mamoru
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.07.2002; Elsevier
• Subjects: Acidic site; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Physical; Co-grinding; Color; Crystallization; Drug Compounding; Drug Stability; Excipients; General pharmacology; Indicators and Reagents; Indomethacin; Indomethacin - chemistry; Magnesium Hydroxide - chemistry; Mechanochemical; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared; Stress, Mechanical; Thermodynamics; X-Ray Diffraction; Mechanochemical; Indomethacin; Co-grinding; Acidic site; Crystallization; Talc; Pharmaceutical technology; Stabilization; Ternary mixture; Indometacin; Solid dispersion; Crystallinity; Amorphous state; Strong acid; Grinding; Silica; Non steroidal antiinflammatory agent; Dosage form; Magnesium hydroxide; Indolacetic acid derivatives
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00196-5

Mechanochemical amorphization of indomethacin (IM) was substantially enhanced by grinding with SiO 2, talc and a Mg(OH) 2–SiO 2 mixture. The rates of the mechanochemical amorphization were in the order of Mg(OH) 2–SiO 2 mixture>talc>SiO 2. Amorphous state stability of IM compounded with the carrier was examined by crystallization behavior under the condition of 30 °C and 11% relative humidity. Superiority of the binary mixture as a carrier was explained in terms of the mechanically induced strong acidic sites of the carrier.