Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems
Background: The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking ag...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Current Research in Pharmacology and Drug Discovery |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259025712500001X |
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| author | Sunitha Sampathi Nitiraj Kulkarni D.V.R.N. Bhikshapathi Jagadish V. Tawade Nainaru Tarakaramu Rzgar Farooq Rashid Aziz Kubaev |
| author_facet | Sunitha Sampathi Nitiraj Kulkarni D.V.R.N. Bhikshapathi Jagadish V. Tawade Nainaru Tarakaramu Rzgar Farooq Rashid Aziz Kubaev |
| author_sort | Sunitha Sampathi |
| collection | DOAJ |
| description | Background: The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking agent. Methods: IBR-loaded HPβCD-NSPs were formulated by optimizing the molar proportion of HPβCD to CDI, as well as stirring rate and duration using a design-based methodology. The synthesized nanoparticles (NSPs) were examined for size, potential, and entrapment of drug. Characterization was performed by X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC), to assess compatibility. Permeability studies were conducted, followed by in vitro and in vivo assessments. Results: The optimized IBR-loaded HPβCD NSPs demonstrated a mean particle size of 145.6 ± 6.8 nm, a PDI of 0.170 ± 0.036, and an EE of 71.04 ± 2.40%. Further validation through zeta sizing, microscopic and spectral analysis, release studies, and pharmacokinetic assessments confirmed the optimization. The HPβCD NSPs demonstrated 14.96 times higher AUC0-t (area under the curve) with a Cmax increase of 6.45 times compared to the free drug, indicating a substantial improvement in bioavailability. Conclusion: IBR-loaded HPβCD NSPs offer a promising strategy for improved drug release and bioavailability, which could significantly benefit melanoma treatment. |
| format | Article |
| id | doaj-art-79795ade9ecc43c3a2b473109bcdbc36 |
| institution | Kabale University |
| issn | 2590-2571 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Pharmacology and Drug Discovery |
| spelling | doaj-art-79795ade9ecc43c3a2b473109bcdbc362025-01-26T05:04:50ZengElsevierCurrent Research in Pharmacology and Drug Discovery2590-25712025-01-018100213Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systemsSunitha Sampathi0Nitiraj Kulkarni1D.V.R.N. Bhikshapathi2Jagadish V. Tawade3Nainaru Tarakaramu4Rzgar Farooq Rashid5Aziz Kubaev6School of Pharmacy, Vishwakarma University, 411048, Pune, Maharashtra, India; Corresponding author.School of Pharmacy, Vishwakarma University, 411048, Pune, Maharashtra, India; Department of Mathematics, Vishwakarma University, Pune, Maharashtra, IndiaTRR College of Pharmacy, Meerpet, Balapur, 500097, Hyderabad, Telangana, IndiaDepartment of Mathematics, Vishwakarma University, Pune, Maharashtra, IndiaDepartment of Mathematics, School of Liberal Arts and Sciences, Mohan Babu University, Sree Sainath Nagar, 517102, Tirupati, Andrapradesh, India; Corresponding author.Department of Medical Laboratory Science, College of Science, Knowledge University, 44001, Erbil, Iraq; Department of Medical Laboratory Technique, College of Medical Technology, AL-Kitab University, Kirkuk, IraqDepartment of Maxillofacial Surgery, Samarkand State Medical University, 18 Amir Temur Street, 140100, Samarkand, UzbekistanBackground: The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking agent. Methods: IBR-loaded HPβCD-NSPs were formulated by optimizing the molar proportion of HPβCD to CDI, as well as stirring rate and duration using a design-based methodology. The synthesized nanoparticles (NSPs) were examined for size, potential, and entrapment of drug. Characterization was performed by X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC), to assess compatibility. Permeability studies were conducted, followed by in vitro and in vivo assessments. Results: The optimized IBR-loaded HPβCD NSPs demonstrated a mean particle size of 145.6 ± 6.8 nm, a PDI of 0.170 ± 0.036, and an EE of 71.04 ± 2.40%. Further validation through zeta sizing, microscopic and spectral analysis, release studies, and pharmacokinetic assessments confirmed the optimization. The HPβCD NSPs demonstrated 14.96 times higher AUC0-t (area under the curve) with a Cmax increase of 6.45 times compared to the free drug, indicating a substantial improvement in bioavailability. Conclusion: IBR-loaded HPβCD NSPs offer a promising strategy for improved drug release and bioavailability, which could significantly benefit melanoma treatment.http://www.sciencedirect.com/science/article/pii/S259025712500001XCross-linker1,1′-carbonyldiimidazoleHydroxypropyl β-cyclodextrinIbrutinibSustained releaseQbD |
| spellingShingle | Sunitha Sampathi Nitiraj Kulkarni D.V.R.N. Bhikshapathi Jagadish V. Tawade Nainaru Tarakaramu Rzgar Farooq Rashid Aziz Kubaev Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems Current Research in Pharmacology and Drug Discovery Cross-linker 1,1′-carbonyldiimidazole Hydroxypropyl β-cyclodextrin Ibrutinib Sustained release QbD |
| title | Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems |
| title_full | Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems |
| title_fullStr | Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems |
| title_full_unstemmed | Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems |
| title_short | Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems |
| title_sort | optimizing ibrutinib bioavailability formulation and assessment of hydroxypropyl β cyclodextrin based nanosponge delivery systems |
| topic | Cross-linker 1,1′-carbonyldiimidazole Hydroxypropyl β-cyclodextrin Ibrutinib Sustained release QbD |
| url | http://www.sciencedirect.com/science/article/pii/S259025712500001X |
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