In vitro–in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol

Jinno, Jun ichi; Kamada, Nanao; Miyake, Masaaki; Yamada, Keigo; Mukai, T.; Odomi, Masaaki; Toguchi, Hajime; Liversidge, Gary G.; Higaki, Kazutaka; Kimura, Takeshi

doi:10.1016/j.jconrel.2008.05.013

Cited by 66 publications

(36 citation statements)

References 35 publications

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“…As per these evaluations, it was concluded that the sample of CIL received was crystalline, polymorphic form A (30,31,34). The purity for CIL was 99.3%.…”

Section: Characterization Cil Receivedmentioning

confidence: 95%

“…The solution was stirred with a rotating paddle at 50 rpm. Samples of 5 ml each were withdrawn from each vessel at predetermined time intervals (5,10,15,30,45,60,120, 180, and 240 min) and filtered through 0.45 μm nylon membrane filter (Axiva, SF1510613, India). At each time point, the same volume of fresh medium was replaced.…”

Section: Inhibition Of Cil Recrystallization From Supersaturated Solumentioning

confidence: 99%

“…CIL is approved as immediate release tablets (only formulation available) in the USA and several European countries under the brand name Pletal® tablets (50 and 100 mg) for the treatment of intermittent claudication (7,27), and it is not surprising that its therapeutic applications are limited due to its poor aqueous solubility and bioavailability (24,25,28). For improving the solubility and dissolution of CIL, the only approach explored so far appears to be particle size reduction (26,(29)(30)(31). Three crystalline forms of CIL have been reported (A, B, and C) where A is the most stable and the other two are metastable (32,33).…”

Section: Introductionmentioning

confidence: 99%

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Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Verma

Rudraraju²

2015

AAPS PharmSciTech

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Abstract. Developing amorphous solid dispersions of water-insoluble molecules using polymeric materials is a well-defined approach to improve the dissolution rate and bioavailability. While the selected polymer plays a vital role in stabilizing the amorphous solid dispersion physically, it is equally important to improve the dissolution profile by inhibiting crystallization from the supersaturated solution generated by dissolution of the amorphous material. Furthermore, understanding the mechanism of dissolution rate enhancement is of vital importance. In this work, wetting kinetics was taken up as an alternative approach for understanding the enhanced dissolution rate for amorphous solid dispersion of a poorly soluble drug. While cilostazol (CIL) was selected as the model drug, povidone (PVP), copovidone, and hypromellose (HPMC) were the polymers of choice. The concentrations against time profiles were evaluated for the supersaturated solutions of CIL in the presence and absence of the selected polymers. The degree of supersaturation increased significantly with increase in polymer content within the solid dispersion. While povidone was found to maintain the highest level of supersaturation for the greatest length of time both in dissolution and solution crystallization experiments, copovidone and hypromellose were found to be the less effective as crystallization inhibitor. The ability of polymers to generate and maintain supersaturated drug solutions was assessed by dissolution studies. The wetting kinetics was compared against the solid dispersion composition to establish a correlation with enhanced dissolution rate.

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“…As per these evaluations, it was concluded that the sample of CIL received was crystalline, polymorphic form A (30,31,34). The purity for CIL was 99.3%.…”

Section: Characterization Cil Receivedmentioning

confidence: 95%

Section: Inhibition Of Cil Recrystallization From Supersaturated Solumentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Verma

Rudraraju²

2015

AAPS PharmSciTech

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“…Therefore, CLZ has been used as a therapeutic agent for the improvement of symptoms in conditions such as cancer (2), pain accompanying chronic arterial obstruction (3), and for the amelioration (4) and, prevention of cerebral infarction (5). The agent is only administered orally because of its low water-solubility (6).…”

Section: Introductionmentioning

confidence: 99%

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

2018

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Abstract. Cilostazol (CLZ), an anti-platelet agent, is primarily used following the onset of cerebral infarction. However, as CLZ is only marginally soluble in water, a strategy for patients with serious secondary conditions, such as impaired consciousness or aphagia, is required. In the present study, topical formulations containing CLZ nanocrystals (CLZ nano ) were designed to enhance percutaneous absorption. In addition, the mechanism of penetration of CLZ nano through rat skin was investigated. A topical formulation containing CLZ nanoparticles (CLZ nano gel patch) was prepared using a combination of recrystallization and ball milling of an aqueous gel. The particle size of CLZ nano was 74.5±6.2 nm (mean ± standard deviation). The concentration of permeated CLZ nano and penetration mechanism of the nanocrystals were measured in a percutaneous absorption experiment. The amount of penetrated CLZ, the penetration rate (J c ), the penetration coefficient through the skin (K p ) and the skin/preparation partition coefficient (K m ) for the CLZ nano gel patch were all significantly higher than those of the CLZ powder (CLZ micro ) gel patch, the CLZ nano ointment and the CLZ micro ointment. In in vitro percutaneous penetration experiments on the CLZ nano gel patches, there was a positive correlation between the number of CLZ nano . Following the application of the CLZ nano gel patch on rat skin, 98% of penetrated CLZ was observed in nanoparticle form; for the CLZ micro gel patch, this figure was 9%. In addition, the CLZ concentrations in the plasma of rats administered the CLZ nano gel patches were significantly higher than those of rats administered the CLZ nano CP gel and PEG ointments. It was suggested that CLZ nano (diameter <100 nm) were transferred through the intracellular spaces in the skin and then into peripheral blood vessels. To the best of our knowledge, this is the first report to elucidate the mechanism of the percutaneous penetration of nanocrystal medicines.

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“…A possible reason is that there still remain many difficulties in developing appropriate dissolution test methods due to fast dissolution of submicron drug substances and in separating undissolved particles from dissolution medium. 28 What is more important is to find a proper dissolution medium that can achieve a good IVIVC.…”

Section: Introductionmentioning

confidence: 99%

In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

Cao¹,

Deng²,

Fu³

et al. 2012

IJN

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Background:The purpose of this study was to develop a sustained drug-release model for water-soluble drugs using silica nanoparticles. Methods: Hollow-type mesoporous silica nanoparticles (HMSNs) were prepared using Na 2 CO 3 solution as the dissolution medium for the first time. The water-soluble compound, silybin meglumine, was used as the model drug. The Wagner-Nelson method was used to calculate the in vivo absorption fraction. Results:The results of transmission electron microscopy and nitrogen adsorption revealed that the empty HMSNs had uniformly distributed particles of size 50-100 nm, a spherical appearance, a large specific surface area (385.89 ± 1.12 m 2 /g), and ultralow mean pore size (2.74 nm). The highly porous structure allowed a large drug-loading rate (58.91% ± 0.39%). In 0.08 M Na 2 CO 3 solution, silybin meglumine-loaded HMSNs could achieve highly efficacious and long-term sustained release for 72 hours in vitro. The results of in vitro-in vivo correlation revealed that HMSNs in 0.08 M Na 2 CO 3 solution had a correlation coefficient R 2 value of 0.9931, while those of artificial gastric juice and artificial intestinal juice were only 0.9287 and 0.7689, respectively. Conclusion:The findings of in vitro-in vivo correlation indicate that HMSNs together with Na 2 CO 3 solution could achieve an excellent linear relationship between in vitro dissolution and in vivo absorption for 72 hours, leading to a promising model for sustained release of watersoluble drugs.

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In vitro–in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol

Cited by 66 publications

References 35 publications

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

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In vitro–in vivo correlation for wet-milled tablet of poorly water-soluble cilostazol

Cited by 66 publications

References 35 publications

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

Enhanced percutaneous absorption of cilostazol nanocrystals using aqueous gel patch systems and clarification of the absorption mechanism

In vitro release and in vitro&ndash;in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles

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Product

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In vitro release and in vitro–in vivo correlation for silybin meglumine incorporated into hollow-type mesoporous silica nanoparticles