Preparation of microcrystals by in situ micronization

Rasenack, Norbert; Steckel, Hartwig; Müller, Bernd W.

doi:10.1016/j.powtec.2004.04.021

Cited by 60 publications

(36 citation statements)

References 13 publications

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“…Since particles are prepared directly in the micronized state (21) and the newly formed microcrystal surface is simultaneously stabilized by a stabilizer (usually a polymer), particles have a much lower tendency for crystal growth and agglomeration (11).…”

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confidence: 99%

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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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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“…[12][13][14] For example, in many applications the shape and size of particles must be carefully controlled to ensure that product performance is consistent from batch to batch. 12,[14][15][16] Furthermore, while the process of generating a desired particle size and morphology profile in a batch of material has traditionally been performed post crystallization through techniques such as milling and micronisation, 17,18 it is more desirable to gain sufficient control of the crystallization step such that crystals with optimum characteristics are grown directly. [18][19][20] For these reasons, focus has recently been directed to gaining further control and understanding of crystallization processes.…”

Section: Introductionmentioning

confidence: 99%

Highly Unusual Triangular Crystals of Theophylline: The Influence of Solvent on the Growth Rates of Polar Crystal Faces

Eddleston

Hejczyk

Cassidy

et al. 2015

Crystal Growth & Design

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A noteworthy feature of the compound theophylline is that it forms crystals with a triangular habit, an extremely rare phenomenon for an organic molecule. Here, we investigate the formation of these crystals, comprised of the polymorph Form II (Pna2 1 ), and demonstrate that the triangles are obtained from solvents which are highly hydrophobic, or which have a hydrogen bond acceptor group and no hydrogen bond donor group. The formation of the triangular crystal habit is rationalized on the basis of the way such solvents interact with the inequivalent (001) and (00-1) polar crystal faces of Form II. Interactions are significantly stronger at one face than the other, inhibiting growth in one direction and limiting crystal growth to a single, triangle shaped, growth sector. This rationalization also enabled interesting surface features observed by atomic force microscopy to be interpreted. Furthermore, we report a second, previously unreported, type of triangular crystal of theophylline for which the angle at the tip of the triangle is obtuse rather than acute. These crystals are proposed, with the aid of transmission electron microscopy and crystal structure prediction, to be a new polymorphic form of theophylline. Kingdom A noteworthy feature of the compound theophylline is that it forms crystals with a triangular habit, an extremely rare phenomenon for an organic molecule. Here, we investigate the formation of these crystals, comprised of the polymorph Form II (Pna2 1 ), and demonstrate that the triangles are obtained from solvents which are highly hydrophobic, or which have a hydrogen bond acceptor group and no hydrogen bond donor group. The formation of the triangular crystal habit is rationalized on the basis of the way such solvents interact with the inequivalent (001) and 4 (00-1) polar crystal faces of Form II. Interactions are significantly stronger at one face than the other, inhibiting growth in one direction and limiting crystal growth to a single, triangle shaped, growth sector. This rationalization also enabled interesting surface features observed by atomic force microscopy to be interpreted. Furthermore, we report a second, previously unreported, type of triangular crystal of theophylline for which the angle at the tip of the triangle is obtuse rather than acute. These crystals are proposed, with the aid of transmission electron microscopy and crystal structure prediction, to be a new polymorphic form of theophylline.

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“…The conventional approaches to produce untrafine drug particles can be divided into top-down and bottom-up techniques (Keck and Müller 2006;Rabinow 2004). In the case of top-down techniques which include jet-milling, pear/ball milling and high pressure homogenising, the bulk drugs are comminuted into micro or nano-sized range using mechanical force (Rasenack et al 2004). However, these techniques need high energy input and exhibit some disadvantages in practice such as contamination of drugs, variation of crystal structures, uncontrolled particle morphology, and broad particle size distribution (Keck and Müller 2006;Kharb et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…However, these techniques need high energy input and exhibit some disadvantages in practice such as contamination of drugs, variation of crystal structures, uncontrolled particle morphology, and broad particle size distribution (Keck and Müller 2006;Kharb et al 2006). In the last decade, bottomup techniques that rely on dissolving the drug in a solvent and precipitating it by the addition of a non-solvent, like supercritical fluid (SCF) technique and liquid precipitation, have been widely investigated to obtain ultrafine drug particles, such as cephradine (Zhong et al 2005), cefuroxime axetil (Zhang et al 2006), danazol (Rogers et al 2002;Zhao et al 2007), ibuprofen (Rasenack et al 2004), etc.…”

Section: Introductionmentioning

confidence: 99%

Nanosuspension for enhancement of oral bioavailability of felodipine

Sahu

Das

2013

Appl Nanosci

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The oral bioavailability of poorly water soluble drug can be improved using nanosuspension. Nanosuspensions are fine dispersion of uniform-sized solid particles in an aqueous vehicle. The present work is aimed at the formulation and evaluation of nanosuspension of felodipine, a poorly water soluble antihypertensive drug. The nanosuspension of felodipine may increase the dissolution rate of drug to improve its oral bioavailability. The nanosuspensions were prepared by nanoprecipitation alone and in combination with ultrasonnication method using ethanol as solvent and water as antisolvent. The prepared nanosuspensions were characterised for particle size, zeta potential, polydispersity index, Scanning electron microscopy (SEM), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behaviour. The effect of variable concentration of drug and stabiliser, ultrasonnication, and solvent to antisolvent ratio on the physical, morphological and dissolution properties of felodipine were studied. The average particle size of felodipine nanoparticles was found to be in the range of 60-330 nm. It was further confirmed by SEM photograph. The particle size varies with increase in concentration of drug and stabiliser. The preparations showed negative zeta potential and polydispersity index in the range of 0.3-0.8. DSC and XRD studies indicated that the crystallinity of precipitated felodipine nanoparticles was markedly lowered than the pure drug. The dissolution of prepared felodipine nanoparticles markedly increased as compared to the original drug. The dissolution profiles of nanosuspension formulation showed up to 79.67 % release in 4 h. It may be concluded that the nanoprecipitation with ultrasonnication have potential to formulate homogenous nanosuspensions with uniform-sized stable nanoparticles of felodipine. The prepared nanosuspension showed enhanced dissolution which may lead to enhanced oral bioavailability of felodipine.

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Preparation of microcrystals by in situ micronization

Cited by 60 publications

References 13 publications

Enhancement in Dissolution Rate of Piroxicam by Two Micronization Techniques

Enhancement in Dissolution Rate of Piroxicam by Two Micronization Techniques

Highly Unusual Triangular Crystals of Theophylline: The Influence of Solvent on the Growth Rates of Polar Crystal Faces

Nanosuspension for enhancement of oral bioavailability of felodipine

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