Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.
Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel 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 poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel 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, Dae-Dong, Gyongsan, Korea.
Sah
Hongkee
H
Jahng
Yurngdong
Y
Chang
Hyeun Wook
HW
Son
Jong-Keun
JK
Lee
Seung Ho
SH
Jeong
Tae Cheon
TC
Rhee
Jong-Dal
JD
Baek
Suk Hwan
SH
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000268:Adhesiveness; D000285:Administration, Rectal; D000818:Animals; D011232:Chemical Precipitation; D004008:Diclofenac / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005782:Gels; D006358:Hot Temperature; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology; D008297:Male; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000737:chemistry; D013488:Suppositories; D013997:Time Factors
D005782:Gels; D013488:Suppositories; D020442:Poloxamer; D004008:Diclofenac; D012965:Sodium Chloride