Rheological characterization and in vivo evaluation of thermosensitive poloxamer-based hydrogel for intramuscular injection of piroxicam.
To develop an industrially practical thermosensitive injectable hydrogel that is easy to administer, gels quickly in the body and allows sustained release of the drug, poloxamer-based hydrogels containing piroxicam as a model drug were prepared with poloxamer, sodium hydroxide and sodium chloride using the cold method. Their rheological characterization, dissolution and pharmacokinetics after intramuscular administration to rabbits were evaluated. Among the ingredients tested, sodium hydroxide and piroxicam decreased the viscosity and retarded the gelation time of the injectable gel. However, sodium chloride did the opposite. The thermosensitive injectable gel composed of 2.5% piroxicam, 15% P 407, 17% P 188, 0.01% sodium hydroxide and 1.6% sodium chloride was instantly applied to practical industrial product, since it was easy to administer intramuscularly and gelled quickly in the body. The drug was dissolved out of the hydrogels by Fickian diffusion through the extramicellar aqueous channels of the gel matrix. Sodium chloride barely affected the dissolution mechanism or dissolution rate of the drug from the injectable gels. Furthermore, it maintained the plasma concentrations of drug for 4 days and gave a 150-fold higher AUC compared to piroxicam solution. Thus, it would be practically useful for delivering piroxicam in a pattern that allows sustained release for a long time, leading to better bioavailability.
Xuan
Jing-Ji
JJ
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Balakrishnan
Prabagar
P
Oh
Dong Hoon
DH
Yeo
Woo Hyun
WH
Park
San Man
SM
Yong
Chul Soon
CS
Choi
Han-Gon
HG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D020100:Hydrogels; D007273:Injections, Intramuscular; D010894:Piroxicam / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D012212:Rheology; D012965:Sodium Chloride / Q000737:chemistry; D012972:Sodium Hydroxide / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014783:Viscosity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D020442:Poloxamer; D010894:Piroxicam; D012965:Sodium Chloride; D012972:Sodium Hydroxide