A comparative study of the in vitro permeation of ibuprofen in mammalian skin, the PAMPA model and silicone membrane
Open accessAbstract
Human skin remains the membrane of choice when conducting in vitro studies to determine dermal penetration of active pharmaceutical ingredients or xenobiotics. However there are ethical and safety issues associated with obtaining human tissue. For these reasons synthetic membranes, cell culture models or in silico predictive algorithms have been researched intensively as alternative approaches to predict dermal exposure in man. Porcine skin has also been recommended as an acceptable surrogate for topical or transdermal delivery research. Here we examine the in vitro permeation of a model active, ibuprofen, using human or porcine skin, as well as the Parallel Artificial Membrane Permeation Assay (PAMPA) model and silicone membrane. Finite dose studies were conducted in all models using commercial ibuprofen formulations and simple volatile ibuprofen solutions. The dose applied in the PAMPA model was also varied in order to determine the amount of applied formulation which best simulates typical amounts of topical products applied by patients or consumers. Permeation studies were conducted up to 6h for PAMPA and silicone and up to 48h for human and porcine skin. Cumulative amounts permeated at 6h were comparable for PAMPA and silicone, ranging from 91 to 136μg/cm(2) across the range of formulations studied. At 48h, maximum ibuprofen permeation in human skin ranged from 11 to 38μg/cm(2) and corresponding values in porcine skin were 59-81μg/cm(2). A dose of 1μL was confirmed as appropriate for finite dose studies in the PAMPA model. The formulation which delivered the greatest amount of ibuprofen in human skin was also significantly more efficient than other formulations when evaluated in the PAMPA model. The PAMPA model also discriminated between different formulation types (i.e. gel versus solution) compared with other models. Overall, the results confirm the more permeable nature of the PAMPA, silicone membrane and porcine tissue models to ibuprofen compared with human skin. Further finite dose studies to elucidate the effects of individual excipients on the barrier properties of the PAMPA model are needed to expand the applications of this model. The range of actives that are suitable for study using the model also needs to be delineated.
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Ibuprofen was more permeable through skin PAMPA and silicone membrane than through human and porcine tissue.
“Luo et al. [20] performed a comparative study of ibuprofen permeation using human and porcine tissue, a skin PAMPA model, and a silicone membrane and found that the drug was more permeable through the PAMPA and the silicone membrane than through the animal tissues.”
From Recreating Human Skin In Vitro: Should the Microbiota Be Taken into Account? (2024) · cites this paper as [20]
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PAMPA—critical factors for better predictions of absorption
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Rahma, A., Lane, M. E., & Sinkó, B. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.122692 · Cited by 12 · see citing works
Self-citationRecreating Human Skin In Vitro: Should the Microbiota Be Taken into Account?
Galvan, A., Pellicciari, C., & Calderan, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021165 · Cited by 11 · see citing works
- Authors
- Luo, L., Patel, A., Sinko, B., Bell, M., Wibawa, J., Hadgraft, J., & Lane, M. E.
- Affiliations
- UCL School of Pharmacy (GB)
- Walgreens Boots Alliance (United Kingdom) (GB)
- Corresponding author
- Lane, Majella E.
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 505
- Issue
- 1-2
- Pages
- 14-19
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2310216621
- Cited by
- 59
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 11 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 2
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- ibuprofen, skin permeation, human skin, porcine skin, silicone membrane, in vitro skin model, topical formulation, transdermal drug delivery
- MeSH terms
- Administration, Cutaneous, Animals, Anti-Inflammatory Agents, Non-Steroidal, Chemistry, Pharmaceutical, Dose-Response Relationship, Drug, Excipients, Humans, Ibuprofen, Membranes, Artificial, Models, Biological, Permeability, Silicones, Skin, Skin Absorption, Swine, Time Factors
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