Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats.
To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.
Yong
Chul Soon
CS
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Oh
Yu-Kyoung
YK
Kim
Yong-Il
YI
Kim
Jong Oh
JO
Yoo
Bong-Kyu
BK
Rhee
Jong-Dal
JD
Lee
Kang Choon
KC
Kim
Dae-Duk
DD
Park
Young-Joon
YJ
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000269:Adhesives; D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D005079:Excipients; D008297:Male; D009092:Mucous Membrane; D020442:Poloxamer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000033:anatomy & histology / Q000187:drug effects; D012995:Solubility; D013488:Suppositories; D013501:Surface-Active Agents
D000269:Adhesives; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D013488:Suppositories; D013501:Surface-Active Agents; D020442:Poloxamer; D004008:Diclofenac