title: Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats.
abstract: 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.
authors: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
authors: Chul Soon
authors: CS
authors: Yong
authors: Yu-Kyoung
authors: YK
authors: Oh
authors: Yong-Il
authors: YI
authors: Kim
authors: Jong Oh
authors: JO
authors: Kim
authors: Bong-Kyu
authors: BK
authors: Yoo
authors: Jong-Dal
authors: JD
authors: Rhee
authors: Kang Choon
authors: KC
authors: Lee
authors: Dae-Duk
authors: DD
authors: Kim
authors: Young-Joon
authors: YJ
authors: Park
authors: Chong-Kook
authors: CK
authors: Kim
authors: Han-Gon
authors: HG
authors: Choi
mesh_terms: 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
chemical_list: D000269:Adhesives; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D013488:Suppositories; D013501:Surface-Active Agents; D020442:Poloxamer; D004008:Diclofenac