Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium

• Published in: International journal of pharmaceutics 2001-09, Vol.226 (1), p.195-205
• Main Authors: Yong, Chul Soon, Choi, Jin Suck, Quan, Qi-Zhe, Rhee, Jong-Dal, Kim, Chong-Kook, Lim, Soo-Jeong, Kim, Kyung-Mi, Oh, Phil-Soo, Choi, Han-Gon
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chemistry, Pharmaceutical; Diclofenac - administration & dosage; Diclofenac sodium; Drug Carriers - chemistry; Excipients; Gels; General pharmacology; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poloxamer - chemistry; Poloxamer gel; Rats; Rats, Sprague-Dawley; Sodium chloride; Sodium Chloride - pharmacology; Suppositories - administration & dosage; Suppositories - chemistry; Temperature; Thermosensitive
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(01)00809-2

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository system containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. The mixtures of P 407 (15%) and P 188 (15–20%) existed as a liquid at room temperature, but gelled at physiological temperature. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable and convenient rectal dosage form for diclofenac sodium.