Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Llusa, Marcos; Levin, Michael; Snee, Ronald D.; Muzzio, Fernando J.

doi:10.1016/j.powtec.2009.10.021

Cited by 34 publications

(9 citation statements)

References 21 publications

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“…As mentioned, the extent of shear during lubricant mixing has been found to affect the tensile strength of products (27)(28)(29)(30)(31)(32)(33)(34)(35) and their dissolution performance (15,36,37). The extent of lubrication (K), introduced by Kushner et al, is a measure developed to establish the direct correlation between mixing history and the amount of lubrication observed in the system (38)(39)(40).…”

Section: Lubrication In Mixing Systemsmentioning

confidence: 99%

“…On the other hand, after lubricants such as MgSt coat larger shear insensitive excipients and APIs, the bonding ability of such particles is reduced, which makes it more difficult to process the material into tablets and often results in weaker tablets (14). Furthermore, given the hydrophobic nature of MgSt, some degree of hydrophobicity may be transferred to ingredients coated with MgSt potentially leading to lower tablet dissolution rates (15).…”

Section: Introductionmentioning

confidence: 99%

“…The researchers quantified the differences in shear by measuring the tablet properties (e.g., Young's modulus and tensile strength) and determined that the amounts of strain in the process were not the same between the batch and continuous process. As mentioned previously, the total amount of strain that is experienced by the blend is a critical factor that defines the coating extent by the shear-sensitive material (14,15). Therefore, controlling the extent of shear during lubricant mixing is critical to ensure that the lubricant is not subjected to excessive strain levels during the blending operation.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders

et al. 2019

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Continuous manufacturing (CM) has clear potential for manufacturing solid oral dosages. It provides several advantages that may aid the manufacturing and quality of drug products. However, one of the main challenges of this technology is the relatively large amount of knowledge required and the amounts of material needed to develop the process during the early stages of development. Early process development evaluations of continuous manufacturing equipment often require larger amounts of material compared with batch, which hinder CM prospect for drugs during the early stages of process development. In this work, a small-scale evaluation of the mixing process occurring in a continuous mixing system was performed. The evaluation involved the use of a small-scale "mixing cell" which was able to replicate the lubrication process of a continuous mixer. It is worth mentioning that we designed the mixing cell by reconfiguration of an existing continuous tubular blender. The extent of lubrication evaluation was performed for three example formulations and was done by mimicking the amount of shear provided to a formulation by means of matching the number of paddle-passes that a formulation experiences within a continuous blending process in the batch mixing cell. The evaluation showed that the small-scale mixing cell was able to replicate the extent of lubrication-evaluated by measuring the tensile strength of compacts being made with both the continuous and mixing cell experiments-occurring in the continuous mixer using a fraction of the amount of materials needed to perform the same evaluation in the continuous blending process.

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Section: Lubrication In Mixing Systemsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders

et al. 2019

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“…Therefore, the hydrophobicity of the raw materials and the effect of processing should be characterized [45,46]. The wettability of a powder can be measured using a modified Washburn technique [47]. The uptake of water into a powder bed due to capillary action was described by Washburn in 1921 [48].…”

Section: Hydrophobicitymentioning

confidence: 99%

A Quantitative Approach to Understand Raw Material Variability

Koynov

Muzzio

2016

Methods in Pharmacology and Toxicology

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The properties of raw materials can affect the properties and quality of intermediates and the final product. The flow behavior of powders, the form of the raw materials for solid oral drug product manufacturing processes, is poorly understood. Thus, the prediction of manufacturability and process performance is difficult. This is further complicated with variability in raw material flow properties. This chapter discusses seven properties typically characterized and the techniques used to measure them. The state of the art in applying this information to define a formulation of manufacturing process is also discussed.

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“…In addition to the data collection and the integration of the continuous manufacturing plant, the highly variable and unpredictable properties of raw materials are necessary to be captured and stored in a database because they could have an impact on the quality of the product [11]. These properties of relevance to continuous manufacturing are measured via many different analytical methods, including FT4 powder characterization [12], particle size analysis [13], Washburn technique [14], etc. The establishment of a raw material property database could be achieved by the "recipe data warehouse" strategy.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Framework for Data Management and Integration in a Continuous Pharmaceutical Manufacturing Processing Line

et al. 2018

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As the pharmaceutical industry seeks more efficient methods for the production of higher value therapeutics, the associated data analysis, data visualization, and predictive modeling require dependable data origination, management, transfer, and integration. As a result, the management and integration of data in a consistent, organized, and reliable manner is a big challenge for the pharmaceutical industry. In this work, an ontological information infrastructure is developed to integrate data within manufacturing plants and analytical laboratories. The ANSI/ISA-88.01 batch control standard has been adapted in this study to deliver a well-defined data structure that will improve the data communication inside the system architecture for continuous processing. All the detailed information of the lab-based experiment and process manufacturing, including equipment, samples and parameters, are documented in the recipe. This recipe model is implemented into a process control system (PCS), data historian, as well as Electronic Laboratory Notebook (ELN) system. Data existing in the recipe can be eventually exported from this system to cloud storage, which could provide a reliable and consistent data source for data visualization, data analysis, or process modeling.

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Measuring the hydrophobicity of lubricated blends of pharmaceutical excipients

Cited by 34 publications

References 21 publications

Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders

Mixing Cell: a Device to Mimic Extent of Lubrication and Shear in Continuous Tubular Blenders

A Quantitative Approach to Understand Raw Material Variability

A Systematic Framework for Data Management and Integration in a Continuous Pharmaceutical Manufacturing Processing Line

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