Microcrystallization of indomethacin using a pH-shift method

Kim, Sung Tae; Kwon, Jai Hyun; Lee, Jae Jeong; Kim, Chan Wha

doi:10.1016/s0378-5173(03)00358-2

Cited by 21 publications

(13 citation statements)

References 10 publications

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“…The same results were obtained in other studies for gliclazide (27), ibuprofen (29), itraconazole and ketoconazol (11), and indomethacine (16). The narrow and uniform size distribution of the particles is one of the important advantages of the microcrystallization process, in contrast with other particle size reduction methods such as milling (16).…”

Section: Particle Size Distribution Of Microcrystalssupporting

confidence: 83%

“…However, mechanical methods such as milling or grinding have inevitable drawbacks, including the tendency of the produced particles to agglomerate, reducing the available surface area (13). In addition, the potential for physical instability or chemical degradation from disruptions in the crystal lattice (14,15) and the high energy input makes this micronization method extremely inefficient (16). Several other methods have been introduced to produce micron-sized drug particles such as high-pressure homogenization (17), supercritical fluid micronization (18,19), liquid-solid techniques (20), and hydrosol formation (11).…”

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confidence: 99%

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Enhancement in Dissolution Rate of Piroxicam by Two Micronization Techniques

Varshosaz¹,

Khajavinia²,

Ghasemlu³

et al. 2013

Dissolution Technol.

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Piroxicam is a nonsteroidal anti-inflammatory drug that is practically insoluble in water. The oral absorption rate of piroxicam is dependent on its dissolution rate in the GI tract. The aim of this study was to enhance the dissolution of piroxicam by a microcrystallization technique. The preparation of microcrystals of piroxicam was done by two methods, solvent change and pH shift. In the solvent-change method, the drug was dissolved in acetone, and the stabilizer was dissolved in water. The aqueous phase was added to acetone under homogenization in an ice bath for 1 min. In the pH-shift method, the drug and stabilizer were both dissolved in 0.1 N NaOH (pH 12) using homogenization. The pH was adjusted to 3 using 0.1 N hydrochloric acid. Dissolution testing was carried out in a hydrochloric acid medium using the rotating basket method. Particle size and morphology, FTIR, DSC, XRD, and surface area of the microcrystals were studied. The effects of drug and stabilizer concentration and homogenization rate on particle size and dissolution efficiency were studied statistically using a D-optimal design. The dissolution efficiency in both methods was increased about 3-to 4-fold. The particle size in both methods was decreased in comparison with untreated drug. Maximum dissolution and minimum particle size were obtained by the solvent-change method. According to the results, both microcrystallization methods are effective in the modification of the crystalline the habit of piroxicam.

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Section: Particle Size Distribution Of Microcrystalssupporting

confidence: 83%

mentioning

confidence: 99%

Enhancement in Dissolution Rate of Piroxicam by Two Micronization Techniques

Varshosaz¹,

Khajavinia²,

Ghasemlu³

et al. 2013

Dissolution Technol.

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show abstract

“…Physical methods such as milling and grinding (4) are successful in particle size reduction; however, the particle size uniformity is not achieved. A common particle size reduction method for hydrophobic drugs is microcrystallization (5). The process is usually used to obtain small particles of the disruption of large crystals.…”

Section: Introductionmentioning

confidence: 99%

“…In situ micronization and microcrystallization are suitable methods for the production of micron-sized drugs (5)(6)(7). Compared with milled products, drug properties are optimized, the particle size is more uniformly distributed, and the powder is less cohesive (5)(6)(7)(8)(9)(10)(11)(12)(13). Gliclazide (GL), 3-(7-azabicyclo [3.3.0] oct-7-yl)-1-(4-methylphenyl)sulfonylurea is a second-generation sulfonylurea, widely used for the treatment of non-insulin-dependent diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Gliclazide Microcrystals Prepared by Two Methods of In Situ Micronization: Pharmacokinetic Studies in Diabetic and Normal Rats

et al. 2010

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Abstract. The low water-solubility of gliclazide (GL) leads to a low dissolution rate and variable bioavailability. The aim of this study was to investigate the effect of micronization on the absorption and pharmacokinetics of GL after oral administration in rats. GL microcrystals were prepared using solventchange and pH-shift methods. Scanning electron microscopy showed considerable changes in the shape and size of crystals using both methods. In the optimized formulation of each method, the particle size of treated GL was reduced about 30 (from 290 to 9.9 μm) and 61 times (to 4.76 μm) by solvent-change and pH-shift methods, respectively. Recrystallized samples showed faster dissolution rate than untreated GL particles. Glucose-lowering effect, C max , and area under the drug concentration-time profile (area under the curve (AUC)) were compared in diabetic and normal rats. AUC and C max were increased by microcrystals in both groups of animals. Administration of 40 mg/kg of GL in the form of untreated drug and microcrystals obtained by solvent-change and pH-shift methods caused 12.49% and 21.04% enhancement in glucose-lowering effect of GL in diabetic rats, respectively.

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“…They include physical methods such as milling and grinding 1 , but it is difficult to obtain uniform fine particles and control the particle size of the drug. Microcrystallization of hydrophobic drugs is a technique to overcome these problems 2 . The process is usually used to obtain small particles by the disruption of large crystals Dissolution rate and bioavailability improvement by micronization of sparingly water-soluble drugs entail using jar mills and fluid energy mills 3 .…”

Section: Introductionmentioning

confidence: 99%