Cremophor-free intravenous microemulsions for paclitaxel II. Stability, in vitro release and pharmacokinetics

Two cremophor-free microemulsion systems LBMW (lecithin:butanol:myvacet:water) and CMW (capmul:myvacet:water), for intravenous (IV) administration of paclitaxel (PAC) were previously developed and characterized. Their chemical stability, in vitro release and pharmacokinetics of PAC were assessed usi...

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Bibliographic Details
Published in:International journal of pharmaceutics 2008-02, Vol.349 (1-2), p.117-123
Main Authors: NORNOO, Adwoa O, CHOW, Diana S.-L
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Area Under Curve
Biological and medical sciences
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid
Data Interpretation, Statistical
Drug Stability
Emulsions
Excipients
General pharmacology
Half-Life
Injections, Intravenous
Male
Medical sciences
Nanoparticles
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethylene Glycols - chemistry
Rats
Rats, Sprague-Dawley
Solubility
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Summary:Two cremophor-free microemulsion systems LBMW (lecithin:butanol:myvacet:water) and CMW (capmul:myvacet:water), for intravenous (IV) administration of paclitaxel (PAC) were previously developed and characterized. Their chemical stability, in vitro release and pharmacokinetics of PAC were assessed using Taxol (cremophor:ethanol 1:1, 6 mg/ml) as a reference. The shelf-lives of PAC at 25 degrees C in Taxol, LBMW and CMW, in an accelerated stability study, were 71, 57 and 31 days, respectively. The activation energy (Ea) for PAC in Taxol, LBMW and CMW was 23, 16 and 14 kcal/mol, respectively. PAC released from LBMW and CMW using a dialysis technique was significantly slower than that from Taxol. The extents of release of PAC from LBMW and CMW were 25 and 50% of that from Taxol. In vivo pharmacokinetic studies in male Sprague-Dawley rats after IV administration revealed that PAC in LBMW and CMW remained in the systemic circulation five and two times longer and was eight and three times more widely distributed than PAC from Taxol. LBMW and CMW offer a significant clinical advantage in terms of the prolonged half-life and wide tissue distribution, indicating that PAC delivered by these systems intravenously may result in prolonged exposure of PAC to the tumor and subsequently an improved clinical efficacy.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2007.07.043