eprintid: 10110994
rev_number: 29
eprint_status: archive
userid: 608
dir: disk0/10/11/09/94
datestamp: 2020-09-30 14:56:57
lastmod: 2021-09-23 22:52:49
status_changed: 2020-09-30 14:56:57
type: article
metadata_visibility: show
creators_name: Iliopoulos, F
creators_name: Caspers, PJ
creators_name: Puppels, GJ
creators_name: Lane, ME
title: Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
divisions: G08
keywords: Confocal Raman Spectroscopy, bioequivalence, in vitro-in vivo correlation, niacinamide, skin
note: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
abstract: Previously, we reported the use of Confocal Raman Spectroscopy (CRS) to investigate the topical delivery of actives and excipients. We have also correlated the results from CRS with findings from in vitro diffusion studies in human skin. However, until now CRS has only been used as a semi-quantitative method of determining the skin uptake of molecules, with results expressed as arbitrary units of signal intensity. Clearly, this posed challenges for using CRS to determine skin delivery and to assess the drug bioavailability and bioequivalence of topical formulations. In the present work, the permeation of niacinamide (NIA) from various formulations in human skin was studied in vitro using conventional Franz cells and in vivo using a quantitative CRS method under finite dose conditions. The selection of NIA was based on its wide use in pharmaceutical and personal care formulations for many years. This is the first fully quantitative study to compare these methods. The vehicles investigated were neat Transcutol® P (TC); binary combinations of propylene glycol (PG) with propylene glycol monolaurate (PGML); and ternary mixtures of PG, PGML, and isopropyl myristate (IPM). These solvents were selected to encompass a range of physicochemical properties. NIA permeation was evident from all formulations in vitro and in vivo. The vehicles PG:PGML and PG:PGML:IPM delivered comparable amounts across the skin in vitro at 24 h (100.3-106.7 µg/cm2, p > 0.05) that were significantly higher compared with those of TC (1.3 µg/cm2, p < 0.05). An excellent in vitro in vivo correlation (R2 = 0.98) was found following the linear regression of the cumulative amounts of NIA permeated in vitro and the amounts of NIA at 2 μm in the skin measured with CRS. A very good correlation between the cumulative permeation of NIA in vitro and the total amount of NIA that penetrated the stratum corneum (SC) per unit of surface area (μg/cm2) in vivo was also observed, with a Pearson correlation coefficient (R2) of 0.94. The findings support the use of CRS for the quantitative measurement of actives delivered to the skin in vivo. Future studies will focus on exploring the reproducibility and reliability of the method by investigating the delivery of different actives from a wider range of vehicles. Additionally, quantitative CRS will be evaluated further as a method for assessing the bioequivalence of topical formulations.
date: 2020-09-18
date_type: published
official_url: http://dx.doi.org/10.3390/pharmaceutics12090887
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1815514
doi: 10.3390/pharmaceutics12090887
pii: pharmaceutics12090887
lyricists_name: Iliopoulos, Fotis
lyricists_name: Lane, Majella
lyricists_id: FILIO03
lyricists_id: MLANE69
actors_name: Dewerpe, Marie
actors_id: MDDEW97
actors_role: owner
full_text_status: public
publication: Pharmaceutics
volume: 12
number: 9
article_number: 887
event_location: Switzerland
citation:        Iliopoulos, F;    Caspers, PJ;    Puppels, GJ;    Lane, ME;      (2020)    Franz Cell Diffusion Testing and Quantitative Confocal Raman Spectroscopy: In Vitro-In Vivo Correlation.                   Pharmaceutics , 12  (9)    , Article 887.  10.3390/pharmaceutics12090887 <https://doi.org/10.3390/pharmaceutics12090887>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10110994/7/pharmaceutics-12-00887-v2.pdf