In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems
Abstract
Objective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach. Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine. Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling. Results: According to the in vitro results, the selected SMEDDS... consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%). Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms.
Keywords:
Self-microemulsifying drug delivery systems (SMEDDS) / simvastatin / poor solubility / absorption simulation / physiologically-based pharmacokinetic modelingSource:
Drug Development and Industrial Pharmacy, 2018, 44, 5, 849-860Publisher:
- Taylor & Francis Ltd, Abingdon
Funding / projects:
- Advanced technologies for controlled release from solid drug delivery systems (RS-MESTD-Technological Development (TD or TR)-34007)
Note:
- Peer-reviewed manuscript: http://farfar.pharmacy.bg.ac.rs/handle/123456789/3430
DOI: 10.1080/03639045.2017.1414835
ISSN: 0363-9045
PubMed: 29228833
WoS: 000426910800017
Scopus: 2-s2.0-85038388404
Collections
Institution/Community
PharmacyTY - JOUR AU - Cetković, Zora AU - Cvijić, Sandra AU - Vasiljević, Dragana PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3178 AB - Objective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach. Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine. Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling. Results: According to the in vitro results, the selected SMEDDS consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%). Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms. PB - Taylor & Francis Ltd, Abingdon T2 - Drug Development and Industrial Pharmacy T1 - In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems VL - 44 IS - 5 SP - 849 EP - 860 DO - 10.1080/03639045.2017.1414835 ER -
@article{ author = "Cetković, Zora and Cvijić, Sandra and Vasiljević, Dragana", year = "2018", abstract = "Objective: The aims of this study were to formulate simvastatin (SV)-loaded self-microemulsifying drug delivery systems (SMEDDS), and explore the potential of these drug delivery systems to improve SV solubility, and also to identify the optimal place in the gastrointestinal (GI) tract for the release of SV using coupled in vitro/in silico approach. Significance: In comparison to other published results, this study considered the extensive pre-systemic clearance of SV, which could significantly decrease its systemic and hepatic bioavailability if SV is delivered into the small intestine. Methods: SV-loaded SMEDDS were formulated using various proportions of oils (PEG 300 oleic glycerides, propylene glycol monocaprylate, propylene glycol monolaurate), surfactant (PEG 400 caprylic/capric glycerides) and cosurfactant (polysorbate 80) and subjected to characterization, and physiologically-based pharmacokinetic (PBPK) modeling. Results: According to the in vitro results, the selected SMEDDS consisted of 10.0% PEG 300 oleic glycerides, 67.5% PEG 400 caprylic/capric glycerides, and 22.5% polysorbate 80. The use of acid-resistant capsules filled with SV-loaded SMEDDS was found helpful in protecting the drug against early degradation in proximal parts of the GI tract, however, in silico simulations indicated that pH-controlled drug release system that dissolve in the distal parts of the intestine might further improve SV bioavailability (up to 7.20%). Conclusion: The obtained results suggested that combined strategy for the improvement of SV bioavailability should comprise solubility enhancement and delayed drug release. The developed SV-specific PBPK model could potentially be used to assess the influence of formulation factors on drug absorption and disposition when developing SV oral dosage forms.", publisher = "Taylor & Francis Ltd, Abingdon", journal = "Drug Development and Industrial Pharmacy", title = "In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems", volume = "44", number = "5", pages = "849-860", doi = "10.1080/03639045.2017.1414835" }
Cetković, Z., Cvijić, S.,& Vasiljević, D.. (2018). In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems. in Drug Development and Industrial Pharmacy Taylor & Francis Ltd, Abingdon., 44(5), 849-860. https://doi.org/10.1080/03639045.2017.1414835
Cetković Z, Cvijić S, Vasiljević D. In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems. in Drug Development and Industrial Pharmacy. 2018;44(5):849-860. doi:10.1080/03639045.2017.1414835 .
Cetković, Zora, Cvijić, Sandra, Vasiljević, Dragana, "In vitro/in silico approach in the development of simvastatin-loaded self-microemulsifying drug delivery systems" in Drug Development and Industrial Pharmacy, 44, no. 5 (2018):849-860, https://doi.org/10.1080/03639045.2017.1414835 . .