Physicochemical characterization and in vivo evaluation of thermosensitive diclofenac liquid suppository.
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 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. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.
Yong
Chul Soon
CS
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, Korea.
Choi
Young-Kwon
YK
Kim
Yong-Il
YI
Park
Byung-Joo
BJ
Quan
Qi-Zhe
QZ
Rhee
Jong-Dal
JD
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000268:Adhesiveness; D000285:Administration, Rectal; D000818:Animals; D019540:Area Under Curve; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D005782:Gels; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum; D012965:Sodium Chloride / Q000737:chemistry; D013488:Suppositories; D013696:Temperature; D013997:Time Factors
D004337:Drug Carriers; D005782:Gels; D013488:Suppositories; D020442:Poloxamer; D004008:Diclofenac; D012965:Sodium Chloride