Incorporation of indomethacin nanoparticles into 3-D ordered macroporous silica for enhanced dissolution and reduced gastric irritancy

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 79; no. 3; pp. 544 - 551
• Main Authors: Hu, Yanchen, Zhi, Zhuangzhi, Wang, Tianyi, Jiang, Tongying, Wang, Siling
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2011; Elsevier
• Subjects: 3-D ordered macroporous silica; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Biological and medical sciences; Chemistry, Pharmaceutical; Drug Carriers - chemistry; Drug Compounding; Drug nanoparticles; Gastric damage; Gastric Mucosa - drug effects; General pharmacology; In vitro dissolution; Indomethacin - administration & dosage; Indomethacin - adverse effects; Indomethacin - chemistry; Medical sciences; Microscopy, Electron, Scanning; Nanoparticles - chemistry; Particle Size; Peptic Ulcer Hemorrhage - chemically induced; Peptic Ulcer Hemorrhage - pathology; Peptic Ulcer Hemorrhage - prevention & control; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Rats; Silicon Dioxide - chemistry; Solubility; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer - chemically induced; Stomach Ulcer - pathology; Stomach Ulcer - prevention & control; Surface Properties; X-Ray Diffraction; Gastric damage; 3-D ordered macroporous silica; Drug nanoparticles; In vitro dissolution; Prostaglandin-endoperoxide synthase; Incorporation; Nanoparticle; Toxicity; Indometacin; Silica; Tocolytic; Indoleacetic acid derivatives; Microparticle; Damaging; Drug; Stomach; Pharmaceutical technology; Enzyme; Enzyme inhibitor; Dissolution; In vitro; Non steroidal antiinflammatory agent; Oxidoreductases; Lesion; Macroporosity
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.07.001

By using the solvent deposition method, large drug crystals can be successfully entrapped into the spherical pores of 3DOM silica in the form of nanoparticles, thus allowing for the proper size control of drug particle size. In the present study, we exploited for the first time the potential of 3-D ordered macroporous (3DOM) silica as matrix for drug nanoparticles, in order to obtain proper control over drug particle size in the sub-micrometer range, enhance the dissolution rate, and reduce gastric damage. 3DOM silica matrix with 3-D spherical pores of 200 nm was successfully created and then loaded with IMC nanoparticles at various drug–silica ratios. A rapid release profile for IMC nanoparticle formulations was achieved in comparison with microsized IMC and a commercial capsule, which could be attributed to both increase in the specific surface area and decrease in the crystallinity of IMC, as well as the hydrophilic surface and the interconnected pore networks of 3DOM silica. Reduced gastric damage of IMC was demonstrated, and the protective effect may arise from the reduction in drug particle size as well as encapsulation effect of 3DOM silica.