Particle engineering of needle shaped crystals by wet milling and temperature cycling: Optimisation for roller compaction

Wilson, David A.; Bunker, Matthew; Milne, David; Jawor-Baczynska, Anna; Powell, Andre; Blyth, J. F.; Streather, David

doi:10.1016/j.powtec.2018.08.023

Cited by 33 publications

(23 citation statements)

References 34 publications

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“…For particle size and shape by static image analysis the Morphologi G3 instrument was chosen 29,31,33,34 . This instrument can accommodate a wide range of particle sizes and shapes relevant to pharmaceutical processing 27 , from micronized materials to granules and agglomerates, and also captures shape factors. Protocols for generating the data were agreed and updated, along with those for data analysis.…”

Section: Selecting Materials and Techniques For The Studymentioning

confidence: 99%

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Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

et al. 2020

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Purpose: Understanding and predicting the flow of bulk pharmaceutical materials could be key in enabling pharmaceutical manufacturing by continuous direct compression (CDC). This study examines whether, by taking powder and bulk measurements, and using statistical modelling, it would be possible the flow of a range of materials likely to be used in CDC. Methods: More than 100 materials were selected for study, from four pharmaceutical companies. Particle properties were measured by static image analysis, powder surface area and surface energy techniques, and flow by shear cell measurements. The data was then analysed and a range of statistical modelling techniques were used, to build predictive models for flow. Results: Using the results from static image analysis a model could be built which allowed the prediction of likely flow in a shear cell, which can be related to performance in a CDC system. Only a small amount of powder was required for the image analysis. Surface area did not add to the precision of the model, and the available surface energy technique did not correlate with flow. Conclusions: A small sample of powder can be examined by Static image analysis, and this data can be used to give an early read on likely flow of a material in a CDC system or other pharmaceutical process, allowing early intervention (if necessary) to improve the characteristics of a material, early in development.

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Section: Selecting Materials and Techniques For The Studymentioning

confidence: 99%

“…Statistical models predicting flow from particle properties have been published previously 26,27 . Initial systems using this data set were built as data became available, using a data analysis workflow enabling data to be integrated into the prediction as new materials where made available by the pharmaceutical consortia.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

et al. 2020

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“…Drug substance’s physical properties such as particle morphology (shape) have a significant impact when designing and developing a robust drug product having envisioned CQAs ( 1 ). The manifestation of needle-shaped API is often considered high risk and a source of difficulty (flowability tends to be minimized, which in turn can negatively impact processing characteristics such as hopper discharge, die filling, and other volumetric dosing operations) in the manufacture of pharmaceutical dosage forms ( 9 ). Drug particle shape can affect downstream processability and cause physical characterization difficulties and drug product performance issues such as a poor dissolution rate or bioavailability ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…The manifestation of needle-shaped API is often considered high risk and a source of difficulty (flowability tends to be minimized, which in turn can negatively impact processing characteristics such as hopper discharge, die filling, and other volumetric dosing operations) in the manufacture of pharmaceutical dosage forms ( 9 ). Drug particle shape can affect downstream processability and cause physical characterization difficulties and drug product performance issues such as a poor dissolution rate or bioavailability ( 9 , 10 ). Particle shape can affect content and dose uniformity, the grittiness of solid particles in chewable tablets, and other properties related to physicochemical stability ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

et al. 2021

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The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder. Graphical Abstract

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Crystallization of Organic Compounds

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Particle engineering of needle shaped crystals by wet milling and temperature cycling: Optimisation for roller compaction

Cited by 33 publications

References 34 publications

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

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