Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles

Nagai, Noriaki; Tanino, Tadatoshi; Ito, Yoshimasa

doi:10.5650/jos.ess16036

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…Dispersions containing ketoprofen nanoparticles were prepared as follows: ketoprofen powder was added to MC solution in purified water, and subjected to wet milling. The milling (3000 rpm, 30 s × 30 times) was performed by a Bead Smash 12 at 4 °C (Wakenyaku Co. Ltd., Kyoto, Japan) [ 20 , 42 ]. The dispersions containing ketoprofen nanoparticles were mixed with carboxypolymethylene, and the gelled-mixture containing ketoprofen nanoparticles was used as the transdermal formulation containing ketoprofen nanoparticles (KET-NPs formulation).…”

Section: Methodsmentioning

confidence: 99%

“…The release of ketoprofen from the KET-NPs formulation was measured as previously reported using a Franz diffusion cell (reservoir volume 12.2 mL) [ 20 , 42 ]. Briefly, 25 nm- or 450 nm-pore size MF TM -MEMBRANE FILTERS (Merck Millipore, Tokyo, Japan) were set in a Franz diffusion cell filled with purified water, and an O -ring flange (1.6 cm i.d.)…”

Section: Methodsmentioning

confidence: 99%

“…Skin penetration from the transdermal formulation was measured by using rat abdominal skin set in the Franz diffusion cell filled with purified water [ 20 , 42 ]. The skin was obtained from 7 week-old Wistar rats following the removal of the hair on the abdominal area on the day prior to the experiment.…”

Section: Methodsmentioning

confidence: 99%

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Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

Nagai

Ogata

Ishii

et al. 2018

IJMS

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We previously designed a novel transdermal formulation containing ketoprofen solid nanoparticles (KET-NPs formulation), and showed that the skin penetration from the KET-NPs formulation was higher than that of a transdermal formulation containing ketoprofen microparticles (KET-MPs formulation). However, the precise mechanism for the skin penetration from the KET-NPs formulation was not clear. In this study we investigated whether energy-dependent endocytosis relates to the transdermal delivery from a 1.5% KET-NPs formulation. Transdermal formulations were prepared by a bead mill method using additives including methylcellulose and carbopol 934. The mean particle size of the ketoprofen nanoparticles was 98.3 nm. Four inhibitors of endocytosis dissolved in 0.5% DMSO (54 μM nystatin, a caveolae-mediated endocytosis inhibitor; 40 μM dynasore, a clathrin-mediated endocytosis inhibitor; 2 μM rottlerin, a macropinocytosis inhibitor; 10 μM cytochalasin D, a phagocytosis inhibitor) were used in this study. In the transdermal penetration study using a Franz diffusion cell, skin penetration through rat skin treated with cytochalasin D was similar to the control (DMSO) group. In contrast to the results for cytochalasin D, skin penetration from the KET-NPs formulation was significantly decreased by treatment with nystatin, dynasore or rottlerin with penetrated ketoprofen concentration-time curves (AUC) values 65%, 69% and 73% of control, respectively. Furthermore, multi-treatment with all three inhibitors (nystatin, dynasore and rottlerin) strongly suppressed the skin penetration from the KET-NPs formulation with an AUC value 13.4% that of the control. In conclusion, we found that caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis are all related to the skin penetration from the KET-NPs formulation. These findings provide significant information for the design of nanomedicines in transdermal formulations.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

Nagai

Ogata

Ishii

et al. 2018

IJMS

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“…We previously reported that drug nanoparticles, such as tranilast [ 19 , 20 ], indomethacin [ 21 , 22 , 23 ], cilostazol [ 24 ], dexamethasone [ 25 ], ketoprofen [ 26 ], ibuprofen [ 27 ], and disulfiram [ 28 , 29 ], can be prepared by bead mill treatment. Therefore, we attempted to design the NIL nano based on our previous findings.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin

Deguchi

Otake

Nakazawa

et al. 2017

IJMS

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Retinopathy leads to irreparable vision loss via capillary closure and areas of nonperfusion. However, the current instillation systems do not allow a sufficient amount of drug required to treat retinopathy to reach the posterior segment (retina); therefore, a new formulation targeting the posterior segment is expected as therapy for retinopathy. We prepared ophthalmic formulations containing nilvadipine nanoparticles (NILnano), and demonstrated whether the instillation of NILnano can prevent retinal dysfunction in rats injected with excessive streptozotocin (STZ rats) in this study. NILnano (mean particle size, 77 nm) was prepared by wet bead mill treatment, with the inclusion of various additives (2-hydroxypropyl-β-cyclodextrin, benzalkonium chloride, d-mannitol, and methylcellulose). Retinal dysfunction was observable two weeks after rats received intraperitoneal injections of streptozotocin (100 mg/kg × 2, consecutive days, STZ rat). Changes in retinal function were evaluated by electroretinogram (ERG) and immunological methods. The retinal thickness, measured as the distance between the ganglion cell layer and the distal border of the outer nuclear layer, increased two weeks after the injection of streptozotocin, resulting in decreases in the levels of a-waves, b-waves, and oscillatory potential amplitudes in ERG of rats. The instillation of NILnano allowed the topical supplement of nilvadipine into the retina, and repeated instillation of NILnano (2 times/day) attenuated the retinal disorders led by the excessive streptozotocin. In conclusion, we found that retinal dysfunction in rats injected with streptozotocin can be prevented by the NILnano instillation. These results are useful in further studies aimed at the therapeutic treatment of retinopathy.

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“…However, ibuprofen has several disadvantages following oral administration, including gastrointestinal irritation, dizziness, headache, peptic ulcer and shows low gastrointestinal absorption due to its low solubility and dissolution rate in water [3]. To reduce these side effects, various dermal dosage forms of ibuprofen, such as patch [4] and gels [5], have been studied.…”

Section: Introductionmentioning

confidence: 99%

Formulation, Optimization and Characterization of Ibuprofen Loaded Microemulsion System Using D-Optimal Mixture Design

et al. 2019

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Objective: The purpose of this study was to develop, optimize and characterize a stable microemulsion, with an improvement of the solubility of a poorly aqueous soluble drug, ibuprofen. Methods: Various oils (oleic acid, cottonseed oil, olive oil, argan oil, and labrafac® WL 1349), surfactants (tween® 80, tween® 40, tween® 20) and co-surfactants including polyethylene glycol 400, ethanol, 1-butanol, and propylene glycol were selected after solubility studies. Then, pseudo-ternary phase diagrams with surfactant/co-surfactant ratio of 1:2, 1:1, 2:1 and 3:1 were constructed and a D-optimal mixture design method was used to optimize the ibuprofen loaded microemulsion. The optimized microemulsion was evaluated for several characteristics including globule size, zeta potential, pH, conductivity, refractive index and stability studies. Results: Optimized microemulsion obtained was composed of oleic acid (6.88% w/w), tween® 80/1-butanol (3:1, 63.11% w/w) and water (30.00% w/w). The results obtained showed an average globule size of 117.5 nm, a zeta potential of-6.47 mV and a transmittance of 96.95±0.77%. The optimized formulation showed an improvement in the solubility of ibuprofen with unchanged characteristics for one month. Conclusion: The use of pseudo-ternary phase diagrams and mathematical modeling allows to obtain an optimal microemulsion with perfect stability for 1 mo and a better solubilization capacity of ibuprofen.

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Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles

Cited by 11 publications

References 27 publications

Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

Involvement of Endocytosis in the Transdermal Penetration Mechanism of Ketoprofen Nanoparticles

Ophthalmic Formulation Containing Nilvadipine Nanoparticles Prevents Retinal Dysfunction in Rats Injected with Streptozotocin

Formulation, Optimization and Characterization of Ibuprofen Loaded Microemulsion System Using D-Optimal Mixture Design

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