Journal article
Microneedle-assisted percutaneous delivery of naltrexone hydrochloride in yucatan minipig: in vitro-in vivo correlation
Molecular pharmaceutics, Vol.10(10), pp.3745-3757
10/07/2013
DOI: 10.1021/mp400227e
PMCID: PMC3848502
PMID: 24053426
Abstract
Although microneedle-assisted transdermal drug delivery has been the subject of multiple scientific investigations, very few attempts have been made to quantitatively relate in vitro and in vivo permeation. The case of naltrexone hydrochloride is not an exception. In the present study, a pharmacokinetic profile obtained following a "poke and patch" microneedle application method in the Yucatan minipig is reported. The profile demonstrates a rapid achievement of maximum naltrexone hydrochloride plasma concentration followed by a relatively abrupt concentration decline. No steady state was achieved in vivo. In an attempt to correlate the present in vivo findings with formerly published in vitro steady-state permeation data, a diffusion-compartmental mathematical model was developed. The model incorporates two parallel permeation pathways, barrier-thickness-dependent diffusional resistance, microchannel closure kinetics, and a pharmacokinetic module. The regression analysis of the pharmacokinetic data demonstrated good agreement with an independently calculated microchannel closure rate and in vitro permeation data. Interestingly, full-thickness rather than split-thickness skin employed in in vitro diffusion experiments provided the best correlation with the in vivo data. Data analysis carried out with the model presented herein provides new mechanistic insight and permits predictions with respect to pharmacokinetics coupled with altered microchannel closure rates.
Details
- Title: Subtitle
- Microneedle-assisted percutaneous delivery of naltrexone hydrochloride in yucatan minipig: in vitro-in vivo correlation
- Creators
- Mikolaj Milewski - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536-0082, United StatesKalpana S PaudelNicole K BrogdenPriyanka GhoshStan L BanksDana C HammellAudra L Stinchcomb
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.10(10), pp.3745-3757
- DOI
- 10.1021/mp400227e
- PMID
- 24053426
- PMCID
- PMC3848502
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Publisher
- United States
- Grant note
- R01 DA013425 / NIDA NIH HHS R01DA13425 / NIDA NIH HHS R42DA32191 / NIDA NIH HHS R42 DA032191 / NIDA NIH HHS
- Language
- English
- Date published
- 10/07/2013
- Academic Unit
- Dermatology; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984025305502771
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