Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug
Abstract
The study elucidated the combined effect of the formulation parameters (the relative contents of the copolymer (poloxamer 407 (P407)), the cosolvent (isopropyl alcohol), and the hydrophobic drug (ibuprofen)) on gelation, applicative properties, drug solubilization capacity and release kinetics of the P407 aqueous solutions under the common conditions of storage and topical administration. The presence of ibuprofen at a therapeutic concentration of 5% enhanced the increase in micellar volume fraction and allowed the gelation of the liquid solutions at P407 concentrations ≥ 15%. Light microscopy, DSC analysis, and rheological measurements pointed that P407 gels with 15–20% of the copolymer enabled controled precipitation of amorphous ibuprofen particles (≤100 μm) in perimicellar microchannels, while gels with 25–30% of P407 as well as increased relative content of the cosolvent in perimicellar aqueous phase, had capacity for complete ibuprofen solubilization. The dissolution of the drug ...particles during the in vitro drug release test, maintained the drug concentration gradient between the perimicellar microchannels and the acceptor medium allowing diffusion-based sustained drug release up to 12 h. The gels with completely solubilized drug notably decrease drug release rate and the cumulative amount of the drug released. Harmonization of the investigated formulation parameters was critical to the formulation of P407 gels that could be promising drug delivery systems for sustained percutaneous delivery of the hydrophobic model drug ibuprofen with reduced frequency of administration and improved patient compliance.
Keywords:
Ibuprofen / Drug solubilization capacity / Gelation behavior / Poloxamer 407 / Sustained drug releaseSource:
Journal of Molecular Liquids, 2020, 303Publisher:
- Elsevier B.V.
Funding / projects:
- Novel encapsulation and enzyme technologies for designing of new biocatalysts and biologically active compounds targeting enhancement of food quality, safety and competitiveness (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-46010)
DOI: 10.1016/j.molliq.2020.112639
ISSN: 0167-7322
WoS: 000533612700076
Scopus: 2-s2.0-85078958400
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Institution/Community
PharmacyTY - JOUR AU - Đekić, Ljiljana AU - Čalija, Bojan AU - Medarević, Đorđe PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3527 AB - The study elucidated the combined effect of the formulation parameters (the relative contents of the copolymer (poloxamer 407 (P407)), the cosolvent (isopropyl alcohol), and the hydrophobic drug (ibuprofen)) on gelation, applicative properties, drug solubilization capacity and release kinetics of the P407 aqueous solutions under the common conditions of storage and topical administration. The presence of ibuprofen at a therapeutic concentration of 5% enhanced the increase in micellar volume fraction and allowed the gelation of the liquid solutions at P407 concentrations ≥ 15%. Light microscopy, DSC analysis, and rheological measurements pointed that P407 gels with 15–20% of the copolymer enabled controled precipitation of amorphous ibuprofen particles (≤100 μm) in perimicellar microchannels, while gels with 25–30% of P407 as well as increased relative content of the cosolvent in perimicellar aqueous phase, had capacity for complete ibuprofen solubilization. The dissolution of the drug particles during the in vitro drug release test, maintained the drug concentration gradient between the perimicellar microchannels and the acceptor medium allowing diffusion-based sustained drug release up to 12 h. The gels with completely solubilized drug notably decrease drug release rate and the cumulative amount of the drug released. Harmonization of the investigated formulation parameters was critical to the formulation of P407 gels that could be promising drug delivery systems for sustained percutaneous delivery of the hydrophobic model drug ibuprofen with reduced frequency of administration and improved patient compliance. PB - Elsevier B.V. T2 - Journal of Molecular Liquids T1 - Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug VL - 303 DO - 10.1016/j.molliq.2020.112639 ER -
@article{ author = "Đekić, Ljiljana and Čalija, Bojan and Medarević, Đorđe", year = "2020", abstract = "The study elucidated the combined effect of the formulation parameters (the relative contents of the copolymer (poloxamer 407 (P407)), the cosolvent (isopropyl alcohol), and the hydrophobic drug (ibuprofen)) on gelation, applicative properties, drug solubilization capacity and release kinetics of the P407 aqueous solutions under the common conditions of storage and topical administration. The presence of ibuprofen at a therapeutic concentration of 5% enhanced the increase in micellar volume fraction and allowed the gelation of the liquid solutions at P407 concentrations ≥ 15%. Light microscopy, DSC analysis, and rheological measurements pointed that P407 gels with 15–20% of the copolymer enabled controled precipitation of amorphous ibuprofen particles (≤100 μm) in perimicellar microchannels, while gels with 25–30% of P407 as well as increased relative content of the cosolvent in perimicellar aqueous phase, had capacity for complete ibuprofen solubilization. The dissolution of the drug particles during the in vitro drug release test, maintained the drug concentration gradient between the perimicellar microchannels and the acceptor medium allowing diffusion-based sustained drug release up to 12 h. The gels with completely solubilized drug notably decrease drug release rate and the cumulative amount of the drug released. Harmonization of the investigated formulation parameters was critical to the formulation of P407 gels that could be promising drug delivery systems for sustained percutaneous delivery of the hydrophobic model drug ibuprofen with reduced frequency of administration and improved patient compliance.", publisher = "Elsevier B.V.", journal = "Journal of Molecular Liquids", title = "Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug", volume = "303", doi = "10.1016/j.molliq.2020.112639" }
Đekić, L., Čalija, B.,& Medarević, Đ.. (2020). Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. in Journal of Molecular Liquids Elsevier B.V.., 303. https://doi.org/10.1016/j.molliq.2020.112639
Đekić L, Čalija B, Medarević Đ. Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug. in Journal of Molecular Liquids. 2020;303. doi:10.1016/j.molliq.2020.112639 .
Đekić, Ljiljana, Čalija, Bojan, Medarević, Đorđe, "Gelation behavior, drug solubilization capacity and release kinetics of poloxamer 407 aqueous solutions: The combined effect of copolymer, cosolvent and hydrophobic drug" in Journal of Molecular Liquids, 303 (2020), https://doi.org/10.1016/j.molliq.2020.112639 . .