Utility of Nanosized Microemulsion for Transdermal Delivery of Tolterodine Tartrate: Ex-Vivo Permeation and In-Vivo Pharmacokinetic Studies

• Published in: Pharmaceutical research 2009-11, Vol.26 (11), p.2446-2453
• Main Authors: Elshafeey, Ahmed H, Kamel, Amany O, Fathallah, Mohsen M
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Administration, Oral; Animals; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - chemistry; Benzhydryl Compounds - metabolism; Benzhydryl Compounds - pharmacokinetics; Benzhydryl Compounds - pharmacology; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chromatography, High Pressure Liquid; Cresols - administration & dosage; Cresols - chemistry; Cresols - metabolism; Cresols - pharmacokinetics; Cresols - pharmacology; Drug Delivery Systems; Drug dosages; Emulsions - chemistry; General pharmacology; Humans; Kinetics; LC/MS/MS; Male; Medical Law; Medical sciences; microemulsion; Nanomaterials; Nanoparticles - chemistry; Permeability; Pharmaceutical technology. Pharmaceutical industry; pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Phenylpropanolamine - administration & dosage; Phenylpropanolamine - chemistry; Phenylpropanolamine - metabolism; Phenylpropanolamine - pharmacokinetics; Phenylpropanolamine - pharmacology; Research Paper; Skin - metabolism; Solvents - chemistry; Swine; Tolterodine Tartrate; transdermal; Transdermal medication; Viscosity
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9956-5

Purpose The aim of this work was to investigate the feasibility of using nanosized microemulsion for transdermal delivery of tolterodine tartrate. Methods The effect of three microemulsions formed by Labrasol: Plurol (3:1), isopropyl myristate and water on the permeation of tolterodine through miniature pig skin was studied in vitro using Franz diffusion cell. For comparison purpose, the effect of different vehicles on the permeation was also studied. Drug pharmacokinetics was studied after transdermal application to human volunteers compared to the commercial oral dosage form using a newly developed LC-MS/MS assay. Results The vehicle PEG 400:Phosphate buffer pH 7.4 in the ratio of 1:1 significantly enhanced tolterodine permeation across pig skin. The microemulsion system (ME3) containing the highest amount of water (50%) significantly enhanced permeation with Q₂₄ of 0.746 mg.cm⁻². In contrast to oral delivery, a sustained activity was observed over a period of 72 h after transdermal application of this microemulsion to human volunteers with significant lower Cmax (1.06 ng/ml), delayed Tmax (3.17 h) and higher MRT value (147.82 h) (p