A control strategy for bioavailability enhancement by size reduction: Effect of micronization conditions on the bulk, surface and blending characteristics of an active pharmaceutical ingredient

Olusanmi, Dolapo; Jayawickrama, Dimuthu A.; Bu, Dongsheng; McGeorge, Gary; Sailes, Helen; Kelleher, Joanne K.; Gamble, John F.; Shah, Umang V.; Tobyn, Mike

doi:10.1016/j.powtec.2014.03.032

Cited by 38 publications

(28 citation statements)

References 39 publications

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“…See [50] frequently applied in the pharmaceutical field for dissolution enhancement of poorly water-soluble drugs. Using this technique, microparticles are produced by reducing large drug crystals down to the micron (<10 μm) range [45][46][47]. Because the dissolution rate of a drug is proportional to its surface area, a major benefit of microcrystallization is enhanced rate of dissolution [48].…”

Section: Resolution Of Inflammation: Capitalizing On Nature's Defensementioning

confidence: 99%

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

et al. 2015

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Inflammation is fundamentally a protective cellular response aimed at removing injurious stimuli and initiating the healing process. However, when prolonged, it can override the bounds of physiological control and becomes destructive. Inflammation is a key element in the pathobiology of chronic pain, neurodegenerative diseases, stroke, spinal cord injury, and neuropsychiatric disorders. Glia, key players in such nervous system disorders, are not only capable of expressing a pro-inflammatory phenotype but respond also to inflammatory signals released from cells of immune origin such as mast cells. Chronic inflammatory processes may be counteracted by a program of resolution that includes the production of lipid mediators endowed with the capacity to switch off inflammation. These naturally occurring lipid signaling molecules include the N-acylethanolamines, N-arachidonoylethanolamine (an endocannabinoid), and its congener N-palmitoylethanolamine (palmitoylethanolamide or PEA). PEA may play a role in maintaining cellular homeostasis when faced with external stressors provoking, for example, inflammation. PEA is efficacious in mast cell-mediated models of neurogenic inflammation and neuropathic pain and is neuroprotective in models of stroke, spinal cord injury, traumatic brain injury, and Parkinson disease. PEA in micronized/ultramicronized form shows superior oral efficacy in inflammatory pain models when compared to naïve PEA. Intriguingly, while PEA has no antioxidant effects per se, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treat neuroinflammation. This review is intended to discuss the role of mast cells and glia in neuroinflammation and strategies to modulate their activation based on leveraging natural mechanisms with the capacity for self-defense against inflammation.

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Section: Resolution Of Inflammation: Capitalizing On Nature's Defensementioning

confidence: 99%

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

et al. 2015

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“…Properties of the API, such as small particle size [8, 9] and needle-like morphology [10, 11] can lead to processing limitations such as poor flowability [12], difficulties with blending [9] as well as undesirable adhesion [13] to surfaces such as tablet punches or feeder walls [14]. These issues are addressed by selecting an appropriate processing route and/or by adding agents like glidants, lubricants or surfactants [15–18].…”

Section: Introductionmentioning

confidence: 99%

A Review of Disintegration Mechanisms and Measurement Techniques

2017

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Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

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“…Incomplete de-aggregation has previously been observed despite the use of much higher mixing speeds (Kale et al, 2009) and significantly longer mixing durations , Olusanmi et al, 2014. Very long blending times may indeed be necessary to fully remove such aggregates in formulations containing poorly water-soluble drug compounds (Nystrom & Westerberg, 1986) which would dramatically reduce the efficiency of the manufacturing process.…”

Section: Blendingmentioning

confidence: 99%

“…Whilst longer mixing times (Kale et al, 2009), higher mixing speeds (De Villiers, 1997, Chaudhuri et al, 2006 and lower fill levels (Sudah et al, 2002, Llusa & Muzzio, 2008 can lead to improvements in the blend homogeneity of cohesive powders, incomplete dispersion of loosely bound aggregates has previously been reported (Olusanmi et al, 2014, Kale et al, 2009. This suggests that the blending process may not be sufficiently aggressive to ensure complete dispersion of aggregates of cohesive APIs within formulated systems.…”

Section: Introductionmentioning

confidence: 99%

Investigation into process-induced de-aggregation of cohesive micronised API particles

Hoffmann

Wray

Gamble

et al. 2015

International Journal of Pharmaceutics

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A control strategy for bioavailability enhancement by size reduction: Effect of micronization conditions on the bulk, surface and blending characteristics of an active pharmaceutical ingredient

Cited by 38 publications

References 39 publications

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

A Review of Disintegration Mechanisms and Measurement Techniques

Investigation into process-induced de-aggregation of cohesive micronised API particles

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