Improvement of solubility and oral bioavailability of a poorly water‐soluble drug, TAS‐301, by its melt‐adsorption on a porous calcium silicate

Kinoshita, Masahiro; Baba, Kazuhiko; Nagayasu, Atushi; Yamabe, Kanoo; Shimooka, Takashi; Takeichi, Yoh'ichiro; Azuma, Mami; Minakuchi, Kazuo

doi:10.1002/jps.10026

Cited by 85 publications

(67 citation statements)

References 10 publications

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“…An increase in solubility of drugs amorphized by coprocessing with silicates has been attributed to the presence of drug in amorphous state (4,5,15,26,31,32). Amorphization alone does not account for all of the dissolution enhancement of co-ground amorphous indomethacin.…”

Section: Discussionmentioning

confidence: 99%

“…The variation in pH and the detection of different polymorphs made further interpretation of the results difficult. Previous studies reporting an increase in the solubility of poorly water soluble drugs by processing with silicates (4,5,31,32) have concluded that the increase is due to amorphization. However, pH variations and polymorphic transformations have not been explicitly accounted for in these studies.…”

Section: Effect Of Dissolution Mediummentioning

confidence: 95%

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Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Bahl

Bogner

2008

AAPS PharmSciTech

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Abstract. The solubility advantage of indomethacin amorphized by co-grinding with Neusilin US2 in various media was investigated. Physical mixtures of γ-indomethacin and Neusilin US2 (in the ratios 1:1, 1:4 and 1:5) were amorphized at room temperature employing 75% RH in a porcelain jar mill using zirconia balls. The crystallinity of the samples was determined using ATR-FTIR and PXRD. The solubility and dissolution profiles of co-ground powders and crystalline counterparts were evaluated in 0.1 N HCl, water and phosphate buffer (pH 6.8) in a USP type II dissolution apparatus at 250 rpm and 37°C. Very high concentrations of dissolved indomethacin as compared to the solubility of γ-indomethacin (~500 times in water and~3.7 times in phosphate buffer) were attained. However, the presence of other polymorphs detected by PXRD and a change in the pH of the medium made interpretation of the results difficult. In 0.1 N HCl the solubility (i.e., the peak in a concentration versus time plot) of the amorphized drug in a 1:5 ratio with Neusilin increased to 109 times the solubility of crystalline γ-indomethacin alone. An increase in amount of drug and Neusilin in the same ratio added to the dissolution medium also increased peak and plateau dissolution concentrations. The presence of silicic acid and ions (Mg 2+ and Al 3+ ) in the dissolution media were found to cause the increase in the plateau concentration of indomethacin. Amorphization alone does not account for all of the dissolution enhancement; acidity, ions, and silicic acid are major contributors to dissolution enhancement.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Dissolution Mediummentioning

confidence: 95%

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Bahl

Bogner

2008

AAPS PharmSciTech

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“…Six et al 14) prepared SDs of itraconazole-Eudragit E100/ PVPVA64 and found that the combination of the two polymers provides an SD with good dissolution properties and improved physical stability compared with the binary SDs of itraconazole. Kinoshita et al 15) prepared SDs of TAS-301, a poorly water-soluble drug, and a porous calcium silicate (FLR) using the twin screw extruder method. The solubility and bioavailability of TAS-301 were markedly enhanced by its melt-adsorption on FLR.…”

mentioning

confidence: 99%

Preparation and Evaluation of Solid Dispersion for Nitrendipine-Carbopol and Nitrendipine-HPMCP Systems Using a Twin Screw Extruder

et al. 2005

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The use of poorly water-soluble drugs has a number of drawbacks, such as increasing the dosage, the administration frequency and the resultant occurrence of side effects. Furthermore, as the rate-limiting step in the absorption process for poorly water-soluble drugs is the dissolution rate of such drugs in the gastrointestinal fluids rather than the rapidity of their diffusion across the gut wall, it is important to improve the oral bioavailability of poorly water-soluble drugs by improving their dissolution rate and solubility. This remains one of the most challenging aspects of drug development.The solid dispersion (SD) method, by which a drug is dispersed in a carrier to make it amorphous, is one of the pharmaceutical approaches most commonly employed to enhance bioavailability of poorly water-soluble drugs. [1][2][3] Various pharmaceutical approaches for the preparation of SDs, including coprecipitation, lyophilization, spray drying, solvent evaporation, fusion and powder mixing methods, have been reported. 4) An important mechanism is the reduction of the drug's particle size to the microcrystalline or molecular level for rapid dissolution and absorption. Broadly speaking, there are three methods of preparing SDs; namely, the fusion method, the solvent process and a combination of these.2) However, the fusion method and solvent method have a number of drawbacks. 5,6) The fusion method requires a high temperature which may result in the decomposition of the drugs, and furthermore, tacky or glassy solids may cause undesirable processing problems. 7) In the solvent method, environmental concerns regarding solvent emissions and heath concerns regarding residual solvent make it necessary to restrict the use of organic solvent. 5)A heating/pressurization/kneading/extruding method using a twin screw extruder is one of the methods proposed for this purpose.8) This extruder, originally designed as an extraction/casting device for polymer alloys in the plastic industry, 9) is now used to process cereals and "functionalize" food materials, such as tissue products from animal protein. 10)This device has already been used successfully to prepare SDs of nifedipine and hydroxypropylmethylcellulosephthalate (HPMCP), 11) itraconazole and hydroxypropylmethylcellulose (HPMC), 12,13) itraconazole and hydroxypropyl-betacyclodextrin (HP-beta-CD) 13) to improve the solubility and dissolution properties of poorly water-soluble drugs. Six et al.14) prepared SDs of itraconazole-Eudragit E100/ PVPVA64 and found that the combination of the two polymers provides an SD with good dissolution properties and improved physical stability compared with the binary SDs of itraconazole. Kinoshita et al. 15) prepared SDs of TAS-301, a poorly water-soluble drug, and a porous calcium silicate (FLR) using the twin screw extruder method. The solubility and bioavailability of TAS-301 were markedly enhanced by its melt-adsorption on FLR.These findings suggest that the twin screw extruder method is a useful technique for preparing SDs and improving th...

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“…Among these methods, adsorption onto porous substrates with a high surface area is a well-known and widely used technique to enhance dissolution of poorly soluble drugs. [10][11][12][13][14] Porous silicate is a porous material that has been commonly used as a pharmaceutical excipient. Several grades of porous silicate having different characteristics such as particle size, pore size, and specific surface area are commercially available and have been widely employed to encapsulate poorly soluble drugs, such as Aerosil [15][16][17][18] Since the discovery of mesoporous (2 nm ,pore size ,50 nm) silica materials in the 1990s, the synthesis and application of mesoporous silica have received substantial attention due to their high surface area, well defined and tunable pore size, uniform porous structure, and easily modified surface.…”

Section: Wang Et Almentioning

confidence: 99%

Ordered nanoporous silica as carriers for improved delivery of water insoluble drugs: a comparative study between three dimensional and two dimensional macroporous silica

Wang¹,

Zhao²,

Hu³

et al. 2013

IJN

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Improvement of solubility and oral bioavailability of a poorly water‐soluble drug, TAS‐301, by its melt‐adsorption on a porous calcium silicate

Cited by 85 publications

References 10 publications

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Preparation and Evaluation of Solid Dispersion for Nitrendipine-Carbopol and Nitrendipine-HPMCP Systems Using a Twin Screw Extruder

Ordered nanoporous silica as carriers for improved delivery of water insoluble drugs: a comparative study between three dimensional and two dimensional macroporous silica

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