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Development of a versatile Nanostructured Lipid Carrier (NLC) using Design of Experiments (DoE) – Part II: Incorporation and stability of butamben with different surfactants
Matarazzo, A.P.; Rios, C.A.; Gerônimo, G.; Ondei, R.; de Paula, E.; Breitkreitz, M.C. Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)—Part II: Incorporation and Stability of Butamben with Different Surfactants. Pharmaceutics2024, 16, 863.
Matarazzo, A.P.; Rios, C.A.; Gerônimo, G.; Ondei, R.; de Paula, E.; Breitkreitz, M.C. Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)—Part II: Incorporation and Stability of Butamben with Different Surfactants. Pharmaceutics 2024, 16, 863.
Matarazzo, A.P.; Rios, C.A.; Gerônimo, G.; Ondei, R.; de Paula, E.; Breitkreitz, M.C. Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)—Part II: Incorporation and Stability of Butamben with Different Surfactants. Pharmaceutics2024, 16, 863.
Matarazzo, A.P.; Rios, C.A.; Gerônimo, G.; Ondei, R.; de Paula, E.; Breitkreitz, M.C. Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)—Part II: Incorporation and Stability of Butamben with Different Surfactants. Pharmaceutics 2024, 16, 863.
Abstract
Nanostructured lipid carriers (NLC) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug according to the Biopharmaceutical Classification System (BCS), it has a log P 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study [1] we have developed a NLC core consisting of solid lipid (CrodamolTM CP), liquid lipid of medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' type of drugs including butamben. In this study, starting from the NLC core formulation previously developed we carried out the optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 2³ factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI) and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped stabilizing the system and decreasing particle size NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI lower than 0.3 and zeta potential above |10|mV. Concerning NLCs stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in aqueous medium.
Keywords
Nanostructured Lipidic Carriers, Design of Experiment, Butamben
Subject
Chemistry and Materials Science, Nanotechnology
Copyright:
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.
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