Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.
OBJECTIVE
Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions.


METHODS
This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro.


RESULTS
The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4.


CONCLUSIONS
All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
Cuilian
C
Peng
Cong
C
Liu
Xing
X
Tang
D000818:Animals; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004655:Emulsions; D005938:Glucocorticoids / Q000737:chemistry* / Q000378:metabolism; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D012995:Solubility; D012996:Solutions; D014222:Triamcinolone Acetonide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D004655:Emulsions; D005938:Glucocorticoids; D011355:Prodrugs; D012996:Solutions; C041990:triamcinolone acetonide 21-palmitate; D014222:Triamcinolone Acetonide