Generation of wear during the production of drug nanosuspensions by wet media milling

Juhnke, Michael; Martin, D. A.; John, Edgar

doi:10.1016/j.ejpb.2012.01.005

Cited by 85 publications

(39 citation statements)

References 40 publications

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“…The elemental Zr levels, quantified as the mass ratio of Zr to milled drug in µg/g, were listed in Table 4. Juhnke et al (2012) found contamination with 100-500 µg/g Zr from three different grades of 100 µm YSZ beads when an undisclosed drug was wet-milled to 140 nm particles (unspecified time and batch size). In our study, Zr contamination was similar in order of magnitude, but reduced by a factor of 21.4 to 47 ± 1.2 µg/g when 50 µm beads were used as opposed to 800 µm beads, which accords well with the general trends in the previous bead wear studies in terms of the impact of bead size (Breitung-Faes and Kwade, 2008;Hennart et al, 2010).…”

Section: Effects Of Bead Size On Wear and Product Contaminationmentioning

confidence: 99%

“…Contamination of the milled product due to bead wear and possible changes in the crystalline state of the drugs are some other concerns (Kesisoglou et al, 2007). Although drug product contamination introduced by typical ceramic and polymeric milling beads are mostly not regulated by health authorities, they should be quantified in the lower ppm range, according to the current regulatory concepts and permitted daily exposures for oral, parenteral, pulmonary and topical administration (Juhnke et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, no first-principle mechanistic understanding of the breakage kinetics has emerged, except that presented in Afolabi et al (2014), and conflicting results about the optimal bead size emerged. Moreover, Cerdeira et al (2011), Ghosh et al (2011, and Juhnke et al (2012) used two-three different bead sizes while investigating the impact of bead size without considering the microhydrodynamics inside the mills. Nonetheless, the studies above overall suggest that sub-100 nm drug nanoparticles may be 6 produced by increasing rotor speed, bead loading, and suspension flow rate.…”

Section: Introductionmentioning

confidence: 99%

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Sub-100nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification

Yaragudi

Afolabi

et al. 2015

Chemical Engineering Science

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Section: Effects Of Bead Size On Wear and Product Contaminationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sub-100nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification

Yaragudi

Afolabi

et al. 2015

Chemical Engineering Science

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“…One of the challenges during this approach is the abrasion of grinding media. The risk of contamination of bead to the product has been minimized by process optimization (14).…”

Section: Introductionmentioning

confidence: 99%

Influence of Critical Parameters of Nanosuspension Formulation on the Permeability of a Poorly Soluble Drug through the Skin—A Case Study

Ghosh

Michniak‐Kohn

2013

AAPS PharmSciTech

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Abstract. In transdermal drug delivery systems, it is always a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems. However, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of nanoparticles and influence of different concentrations of solubilizer such as vitamin E TPGS (D-a-tocopheryl polyethylene glycol 1000 succinate) to improve the permeation rate through the skin. Effects of several formulation factors were studied on the nanosuspension systems using ibuprofen as a model drug. The overall permeation enhancement process through the skin was influenced mostly by the solubilizer and also by the size of nanoparticles. The gel formulation developed with vitamin E TPGS+HPMC nanosuspension, consequently represent a promising approach aiming to improve the permeability performance of a poorly water soluble drug candidate.

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“…Both of these methods require high energy consumption and long cycle time especially at the manufacturing scale. Another disadvantage of wet media milling is the risk of contamination due to media wear (22) and phase transition of drug induced by high mechanical stresses (23). Despite these disadvantages, wet stirred media milling has been preferred over other top-down methods in the pharmaceutical industry as it is continuous, scalable, solvent-free, and environmentally benign (24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

An Intensified Vibratory Milling Process for Enhancing the Breakage Kinetics during the Preparation of Drug Nanosuspensions

Zhang

Davé

et al. 2015

AAPS PharmSciTech

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Abstract. As a drug-sparing approach in early development, vibratory milling has been used for the preparation of nanosuspensions of poorly water-soluble drugs. The aim of this study was to intensify this process through a systematic increase in vibration intensity and bead loading with the optimal bead size for faster production. Griseofulvin, a poorly water-soluble drug, was wet-milled using yttrium-stabilized zirconia beads with sizes ranging from 50 to 1500 μm at low power density (0.87 W/g). Then, this process was intensified with the optimal bead size by sequentially increasing vibration intensity and bead loading. Additional experiments with several bead sizes were performed at high power density (16 W/g), and the results were compared to those from wet stirred media milling. Laser diffraction, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and dissolution tests were used for characterization. Results for the low power density indicated 800 μm as the optimal bead size which led to a median size of 545 nm with more than 10% of the drug particles greater than 1.8 μm albeit the fastest breakage. An increase in either vibration intensity or bead loading resulted in faster breakage. The most intensified process led to 90% of the particles being smaller than 300 nm. At the high power intensity, 400 μm beads were optimal, which enhanced griseofulvin dissolution significantly and signified the importance of bead size in view of the power density. Only the optimally intensified vibratory milling led to a comparable nanosuspension to that prepared by the stirred media milling.

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Generation of wear during the production of drug nanosuspensions by wet media milling

Cited by 85 publications

References 40 publications

Sub-100nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification

Sub-100nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification

Influence of Critical Parameters of Nanosuspension Formulation on the Permeability of a Poorly Soluble Drug through the Skin—A Case Study

An Intensified Vibratory Milling Process for Enhancing the Breakage Kinetics during the Preparation of Drug Nanosuspensions

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