Journal article
Examination of the Rate and Extent of Drug Released from Commercial Topical Delivery Systems During Wear: An Example with Lidocaine Topical Systems
Pharmaceutical research, Vol.41(1), pp.39-50
01/2024
DOI: 10.1007/s11095-023-03617-7
Abstract
OBJECTIVEThis study aimed to determine the extent and rate of lidocaine released in vivo from two bioequivalent topical delivery systems (TDS) by using complementary assessments: pharmacokinetic analysis in healthy human volunteers, and residual lidocaine in TDS following 12 h of wear. The goal was to explore a potentially more clinically meaningful strength presentation than percent active pharmaceutical ingredient loaded in topical systems. METHODSA three-arm, open-label, crossover clinical study was conducted in 23 human subjects, with 5% lidocaine topical systems from two manufacturers, and intravenous lidocaine administration. Residual drug and LC-MS/MS analyses were performed on worn TDS and serum samples. The rate and extent of drug released from the TDS during wear were determined through (1) calculations of consumed lidocaine via analysis of residual drug in worn TDS, and (2) a pharmacokinetic approach via derivation of the absolute clearance and serum lidocaine concentration at steady state. RESULTSOverall the pharmacokinetic approach underestimated the amount transferred to the subject and exhibited greater variability, which may relate to natural inter-subject variability in pharmacokinetic parameters. Further, lidocaine TDS are intended for localized, not systemic, delivery and this may also explain some of the variability seen in the systemic serum concentrations. CONCLUSIONSThe residual drug and pharmacokinetic approaches align well for transdermal formulations, but the differences in administration route (topical versus transdermal) all but eliminates the potential use of the pharmacokinetic approach unless additional compartmental modeling is explored.
Details
- Title: Subtitle
- Examination of the Rate and Extent of Drug Released from Commercial Topical Delivery Systems During Wear: An Example with Lidocaine Topical Systems
- Creators
- Qing Cai - Long Island UniversityArmita Azarpanah - Long Island UniversityJayshil A Bhatt - Long Island UniversityHui WeiJamie Carr - University of Iowa Hospitals and ClinicsKenneth R Morris - Long Island UniversityCaroline Strasinger - United States Food and Drug AdministrationNicole K Brogden - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Pharmaceutical research, Vol.41(1), pp.39-50
- DOI
- 10.1007/s11095-023-03617-7
- ISSN
- 0724-8741
- eISSN
- 1573-904X
- Grant note
- name: National Institute for Pharmaceutical Technology and Education, award: 5U01FD004275; DOI: 10.13039/100000002, name: The National Institutes of Health, award: CTSA U54R001356
- Language
- English
- Electronic publication date
- 10/17/2023
- Date published
- 01/2024
- Academic Unit
- Dermatology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984482455402771
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