Preparation of nanosuspensions of a 1,4-dihydropyridine-based mixed L-/T-type calcium channel blocker by combined precipitation and ultrasonication methods

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dc.authoridOzturk, Naile/0000-0002-7617-8433
dc.authoridGunduz, Miyase Gozde/0000-0002-2287-9509
dc.authorid, Esra Pezik/0000-0002-4713-1249
dc.authorwosidGULSUN, TUGBA/J-1050-2013
dc.authorwosidOzturk, Naile/F-3650-2017
dc.authorwosidGunduz, Miyase Gozde/H-5541-2016
dc.contributor.authorPezik, Esra
dc.contributor.authorGulsun, Tugba
dc.contributor.authorGunduz, Miyase Gozde
dc.contributor.authorSahin, Selma
dc.contributor.authorOzturk, Naile
dc.contributor.authorVural, Imran
dc.date.accessioned2024-08-04T20:54:32Z
dc.date.available2024-08-04T20:54:32Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractM3, a condensed 1,4-dihydropyridine (DHP) derivative, targets both L- and T-type calcium channels and therefore, stands as a promising antihypertensive drug candidate. This study aims to improve the poor solubility of M3 using nanocrystal technology (a combination of precipitation and ultrasonication methods) to enhance its oral bioavailability. Pre-formulation studies were performed and M3 nanosuspensions were prepared using different stabilizers (polyvinyl pyrrolidone K30, polyvinyl alcohol, SoluPlus & REG;) and surfactants (poloxamer 188, poloxamer 407, sodium deoxycholate, sodium lauryl sulfate) at different concentrations (0.05, 0.1, 0.5, 1.0, 2.0%, w/v). The optimum nanosuspension formulation was freeze-dried using different cryoprotectants (mannitol, trehalose, glucose, sucrose, dextran) at different ratios (1.25, 2.5, 5.0%, w/v). It was determined that the most suitable cryoprotectant and ratio was 5.0% trehalose, resulting in nanocrystals with a size of 320.2 & PLUSMN; 15.3 nm and a zeta potential of -27.4 & PLUSMN; 0.1 mV. The physicochemical properties of M3, poloxamer 188, physical mixture and freeze-dried nanocrystals were evaluated by XRD, DSC and FT-IR analyses. Characterization studies showed amorphization of M3 in the freeze-dried nanocrystals prepared with poloxamer 188. The result of equilibrium solubility and permeability studies results indicated that M3 could be a BCS class 4 compound. Cell culture studies using Caco-2 cells showed that M3 had no significant toxic effect on the cells and had a Papp value of 2.2 x 10-7 cm/s. Compared to coarse M3 powder freeze-dried M3 nanocrystals showed a 200-fold increase in solubility and a 28.6-fold increase in apparent permeability. The cytotoxic effect of M3 was also reduced by using poloxamers as stabilizers in the formulation. M3 nanosuspensions were found to be a promising candidate for the oral administration of M3 for the potential treatment of hypertension due to the increase in solubility and permeability which could enhance its oral bioavailability.en_US
dc.description.sponsorshipHacettepe Scientific Research Projects Coordination Unit [THD-2019-18409]en_US
dc.description.sponsorshipThis research was supported by a grant from Hacettepe Scientific Research Projects Coordination Unit (THD-2019-18409) .en_US
dc.identifier.doi10.1016/j.jddst.2023.104772
dc.identifier.issn1773-2247
dc.identifier.issn2588-8943
dc.identifier.scopus2-s2.0-85165586613en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.jddst.2023.104772
dc.identifier.urihttps://hdl.handle.net/11616/101482
dc.identifier.volume87en_US
dc.identifier.wosWOS:001048435400001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Drug Delivery Science and Technologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectEquilibrium solubilityen_US
dc.subjectHexahydroquinolineen_US
dc.subjectHypertensionen_US
dc.subjectNanocrystalsen_US
dc.subjectNanosuspensionen_US
dc.subjectPermeabilityen_US
dc.titlePreparation of nanosuspensions of a 1,4-dihydropyridine-based mixed L-/T-type calcium channel blocker by combined precipitation and ultrasonication methodsen_US
dc.typeArticleen_US

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