Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate
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2021
Authors
Bubić-Pajić, NatašaaVucen, Sonja
Ilić, Tanja
O'Mahony, Conor
Dobričić, Vladimir
Savić, Snežana
Article (Published version)
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The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug – sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer – dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics. A penetration enhancement efficacy of MNs was evaluated in vitro using porcine ear skin in parallel with the efficacy of formerly developed chemical penetration enhancer – biocompatible microemulsion (ME) formulation. Moreover, an ability of solid silicon MNs to significantly improve delivery of SN from ME into the skin has also been investigated. The obtained results showed that dissolving MNs had satisfying morphological properties and mechanical strength. This type of MNs provided comparable drug deposition in the sk...in as ME formulation, but also revealed an indication of percutaneous absorption of a portion of the administered drug dose. However, the penetration/permeation study results were largely influenced by experimental setup and dosing regimen. Although solid silicon MNs assisted SN dermal delivery led to increase of drug cutaneous retention (1.9-fold) under infinite dosing regimen, the synergistic action of solid MNs and ME applied under finite dosing was more pronounced in comparison with the application either of physical (dissolving MNs) or chemical enhancer (ME) alone. Namely, SN amount accumulated into the skin increased up to 4.67 and 4.37 folds in comparison with ME and dissolving MNs alone, respectively, while reaching a significant decrease in drug permeation through the skin compared to the use of dissolving MNs. Application of ME per se was the only approach that provided selective in vitro dermal drug delivery without SN permeation across the skin. However, despite both types of the used MNs lead to SN permeation in vitro, the ratio between the drug amount deposited in the skin and SN content permeated was significantly higher for the combined approach (12.05) than for dissolving MNs (2.10). Therefore, a combination of solid silicon MNs and biocompatible ME favoured more pronouncedly SN skin accumulation, which is preferable in the treatment of skin fungal infections.
Keywords:
Microemulsion / Dissolving microneedles / Penetration enhancer / Sertaconazole nitrate / Solid microneedlesSource:
European Journal of Pharmaceutical Sciences, 2021, 164Publisher:
- Elsevier B.V.
Funding / projects:
DOI: 10.1016/j.ejps.2021.105895
ISSN: 0928-0987
WoS: 000743728300001
Scopus: 2-s2.0-85107812089
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107812089&doi=10.1016%2fj.ejps.2021.105895&partnerID=40&md5=a409a1a7ca76c80e0ca229da5383b22fhttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3914
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PharmacyTY - JOUR AU - Bubić-Pajić, Natašaa AU - Vucen, Sonja AU - Ilić, Tanja AU - O'Mahony, Conor AU - Dobričić, Vladimir AU - Savić, Snežana PY - 2021 UR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107812089&doi=10.1016%2fj.ejps.2021.105895&partnerID=40&md5=a409a1a7ca76c80e0ca229da5383b22f UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3914 AB - The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug – sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer – dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics. A penetration enhancement efficacy of MNs was evaluated in vitro using porcine ear skin in parallel with the efficacy of formerly developed chemical penetration enhancer – biocompatible microemulsion (ME) formulation. Moreover, an ability of solid silicon MNs to significantly improve delivery of SN from ME into the skin has also been investigated. The obtained results showed that dissolving MNs had satisfying morphological properties and mechanical strength. This type of MNs provided comparable drug deposition in the skin as ME formulation, but also revealed an indication of percutaneous absorption of a portion of the administered drug dose. However, the penetration/permeation study results were largely influenced by experimental setup and dosing regimen. Although solid silicon MNs assisted SN dermal delivery led to increase of drug cutaneous retention (1.9-fold) under infinite dosing regimen, the synergistic action of solid MNs and ME applied under finite dosing was more pronounced in comparison with the application either of physical (dissolving MNs) or chemical enhancer (ME) alone. Namely, SN amount accumulated into the skin increased up to 4.67 and 4.37 folds in comparison with ME and dissolving MNs alone, respectively, while reaching a significant decrease in drug permeation through the skin compared to the use of dissolving MNs. Application of ME per se was the only approach that provided selective in vitro dermal drug delivery without SN permeation across the skin. However, despite both types of the used MNs lead to SN permeation in vitro, the ratio between the drug amount deposited in the skin and SN content permeated was significantly higher for the combined approach (12.05) than for dissolving MNs (2.10). Therefore, a combination of solid silicon MNs and biocompatible ME favoured more pronouncedly SN skin accumulation, which is preferable in the treatment of skin fungal infections. PB - Elsevier B.V. T2 - European Journal of Pharmaceutical Sciences T1 - Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate VL - 164 DO - 10.1016/j.ejps.2021.105895 ER -
@article{ author = "Bubić-Pajić, Natašaa and Vucen, Sonja and Ilić, Tanja and O'Mahony, Conor and Dobričić, Vladimir and Savić, Snežana", year = "2021", abstract = "The aim of this study was to compare the efficacy of different approaches for enhancement of dermal availability of the highly lipophilic antifungal model drug – sertaconazole nitrate (SN). For this purpose, a physical penetration enhancer – dissolving microneedles (MNs) was fabricated by filling moulds with liquid formulation based on polyvinylpyrrolidone and loaded with SN. Dissolving MNs were characterised regarding their morphological and mechanical characteristics. A penetration enhancement efficacy of MNs was evaluated in vitro using porcine ear skin in parallel with the efficacy of formerly developed chemical penetration enhancer – biocompatible microemulsion (ME) formulation. Moreover, an ability of solid silicon MNs to significantly improve delivery of SN from ME into the skin has also been investigated. The obtained results showed that dissolving MNs had satisfying morphological properties and mechanical strength. This type of MNs provided comparable drug deposition in the skin as ME formulation, but also revealed an indication of percutaneous absorption of a portion of the administered drug dose. However, the penetration/permeation study results were largely influenced by experimental setup and dosing regimen. Although solid silicon MNs assisted SN dermal delivery led to increase of drug cutaneous retention (1.9-fold) under infinite dosing regimen, the synergistic action of solid MNs and ME applied under finite dosing was more pronounced in comparison with the application either of physical (dissolving MNs) or chemical enhancer (ME) alone. Namely, SN amount accumulated into the skin increased up to 4.67 and 4.37 folds in comparison with ME and dissolving MNs alone, respectively, while reaching a significant decrease in drug permeation through the skin compared to the use of dissolving MNs. Application of ME per se was the only approach that provided selective in vitro dermal drug delivery without SN permeation across the skin. However, despite both types of the used MNs lead to SN permeation in vitro, the ratio between the drug amount deposited in the skin and SN content permeated was significantly higher for the combined approach (12.05) than for dissolving MNs (2.10). Therefore, a combination of solid silicon MNs and biocompatible ME favoured more pronouncedly SN skin accumulation, which is preferable in the treatment of skin fungal infections.", publisher = "Elsevier B.V.", journal = "European Journal of Pharmaceutical Sciences", title = "Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate", volume = "164", doi = "10.1016/j.ejps.2021.105895" }
Bubić-Pajić, N., Vucen, S., Ilić, T., O'Mahony, C., Dobričić, V.,& Savić, S.. (2021). Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate. in European Journal of Pharmaceutical Sciences Elsevier B.V.., 164. https://doi.org/10.1016/j.ejps.2021.105895
Bubić-Pajić N, Vucen S, Ilić T, O'Mahony C, Dobričić V, Savić S. Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate. in European Journal of Pharmaceutical Sciences. 2021;164. doi:10.1016/j.ejps.2021.105895 .
Bubić-Pajić, Natašaa, Vucen, Sonja, Ilić, Tanja, O'Mahony, Conor, Dobričić, Vladimir, Savić, Snežana, "Comparative efficacy evaluation of different penetration enhancement strategies for dermal delivery of poorly soluble drugs – A case with sertaconazole nitrate" in European Journal of Pharmaceutical Sciences, 164 (2021), https://doi.org/10.1016/j.ejps.2021.105895 . .