Effect of sodium chloride on the release, absorption and safety of diclofenac sodium delivered by poloxamer gel.
Poloxamer solutions prepared with poloxamers and sodium chloride were previously reported to undergo a phase transition to bioadhesive gels at body temperature. For the development of a thermosensitive diclofenac sodium-loaded poloxamer gel, here we investigated the effect of sodium chloride on the release, safety and rectal absorption in rats of diclofenac sodium delivered by the poloxamer gels. P 188 delayed the release rates of diclofenac sodium from poloxamer gels. However, sodium chloride showed no significant effect on the release rates of diclofenac sodium from poloxamer gels. Release mechanism analysis showed the release of diclofenac sodium was proportional to the time. The initial plasma concentrations of diclofenac sodium in the rectal formulation [diclofenac sodium/poloxamer 407 (P 407)/poloxamer 188 (P 188)/sodium chloride (2.5/15/17/0.8%)] were significantly higher compared with those in semi-solid suppository. Furthermore, it gave significantly faster Tmax of diclofenac sodium than did semi-solid suppository, indicating that the diclofenac sodium from poloxamer gel could be absorbed faster than that from semi-solid one in rats. It did not cause any morphological damage to the rectal tissues. These results suggested that poloxamer gel with sodium chloride could be a more effective and safe rectal delivery system of diclofenac sodium.
Park
Young-Joon
YJ
College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
Yong
Chul Soon
CS
Kim
Hak-Mi
HM
Rhee
Jong-Dal
JD
Oh
Yu-Kyoung
YK
Kim
Chong-Kook
CK
Choi
Han-Gon
HG
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D008297:Male; D020442:Poloxamer / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics*
D005782:Gels; D020442:Poloxamer; D004008:Diclofenac; D012965:Sodium Chloride