Laboratory methods for assessing API sensitivity to mechanical stress during agitated drying (original) (raw)
Related papers
Perspective Chapter: Pharmaceutical Drying
IntechOpen eBooks, 2023
This chapter presents an overview of the perspective chapter on pharmaceutical drying within the context of drug manufacturing. It explores the significance of pharmaceutical drying in ensuring the stability and efficacy of drug products. The chapter begins by defining pharmaceutical drying and emphasizing its importance in the manufacturing process. Various methods of pharmaceutical drying, including air drying, vacuum drying, freeze-drying, and spray drying, are discussed, and a comparison between these methods is provided. Factors that influence pharmaceutical drying, such as physical and chemical properties of the product, drying temperature, drying time, pressure, humidity, and solvent properties, are examined. The chapter also highlights the challenges associated with pharmaceutical drying, including product stability and degradation, loss of potency, residual solvents, and the formation of amorphous or crystalline solids. Strategies to overcome these challenges, such as process optimization, the use of drying aids, control of drying parameters, and formulation considerations, are explored. Quality control measures in pharmaceutical drying, including the monitoring of residual moisture and solvent levels, characterization of dried products, and adherence to regulatory guidelines, are discussed.
Powders
In the last decade, twin-screw wet granulation became an essential technology for continuous pharmaceutical tablet production. Consequently, interest in (semi-)continuous fluidized bed drying systems as a subsequent processing unit has grown. In parallel, it has become pivotal to fully understand and control manufacturing processes in line with in the quality-by-design paradigm. Formulation-generic prediction models would enormously facilitate digitally enhanced process development and require dedicated experimental data collection and process knowledge. To obtain this knowledge, three experimental campaigns were performed in this work. Firstly, an investigation into the effect of dryer process settings on drying behavior is presented. Secondly, the effect of active pharmaceutical ingredient properties on drying was assessed by producing granules of similar particle size and porosity and evaluating their drying and breakage behavior. Finally, additional experiments with varying acti...
Spray Drying in Pharmaceutical Industry: A Review
Spray drying is an interesting manufacturing technique for the pharmaceutical industry since it uses a one-step process for formation and drying of powders. Using this technique the number of unit operations is reduced, improving production efficiency and reducing costs, especially since spray drying is a technique which can be easily automated and equipped for in-line product analysis. In addition, spray drying can be considered a continuous process, thus reducing time-to-market because of scale-up benefits and better quality. Spray drying has a wide range of applications in the pharmaceutical and biotech industry. It is a convenient method to produce (coprocessed) excipients. Spray drying is applied to improve the compactability of drugs and to perform microencapsulation, granulation and complex formation. In addition, spray drying is successfully used for the modification of biopharmaceutical properties and the formulation of dry powder aerosols and heat sensitive materials.
European Journal of Pharmaceutical Sciences, 2018
Spray drying is increasingly becoming recognized as an efficient drying and formulation technique for pharmaceutical and biopharmaceutical processing. It offers significant economic and processing advantages compared to lyophilisation/freeze-drying techniques even though the optimisation of process parameters is often a costly and time-consuming procedure. Spray Drying has primarily been used in formulating small molecule drugs with low solubility however it is increasingly being applied to the processing of large biomolecules and biopharmaceuticals. This review examines the basics of spray drying process, current technology and various components used in spray drying process. Moreover, it is focused on introducing critical formulation and processing factors in spray drying of small molecule drugs and large biomolecules, their similarities and differences. Finally, it provides an overview of the experimental optimisation strategies designed to achieve optimum spray drying results in the shortest possible timeframe while utilising minimum product.
Spray Drying in the Pharmaceutical Industry – A Review
2011
Spray drying is a technique which has a wide range of applications in the pharmaceutical<br> industry. The unique possibilities for particle engineering, potent drug handling and<br> continuous production makes spray drying the preferred tool in formulation departments in<br> more and more companies. The present review highlights the instrumentation, advantages<br> and the various applications of spray drying.
2020
Experiments have been carried out to study the effect of agitation on particle size distribution of aspirin powder and aspirin agglomerates during vacuum contact agitated drying. Morphology G3 by Malvern was used to find the size distribution of the materials under investigation before and after the drying process at 0.1, 0.5 and 0.9 µm. It was found that due to agitation, aspirin powder portrayed from negligible to significant agglomeration dependent on the diameter of the material under investigation. While attrition and agglomeration compete together during the drying process of aspirin agglomerates, with attrition dominating at 0.1 and 0.5µm and agglomeration at 0.9 µm.
Journal of Pharmaceutical Sciences, 2012
During the drying process of a wet granulate, water-soluble compounds can migrate to the outer layers of the granule with the evaporating solvent. This migration can affect structural and mechanical characteristics of the granules as the solute accumulates on the granule's outer crust. The objective of this study was to compare the effect of the fluidized bed and oven tray at different drying temperatures on the characteristics of intragranular migration. The extent of migration and the migration effect on granule structure and granule strength were investigated using light microscopy and computerized X-ray microtomography, in both qualitative and quantitative terms. In addition, a mechanical tester was used to assess granule strength and granule failure type. Multivariate analysis of variance with a followup discriminant analysis was conducted to investigate the effect of the drying method and the drying temperature on the granule structure. There were significant differences in the intragranular distribution of water-soluble compound as well as in the granule structures and mechanical properties between the drying methods, where drying temperature had only a marginal effect.
Journal of Pharmaceutical Investigation
Background Most biopharmaceuticals are developed in liquid dosage forms that are less stable than solid forms. To ensure the stability of biopharmaceuticals, it is critical to use an effective drying technique in the presence of an appropriate stabilizing excipient. Various drying techniques are available for this purpose, such as freeze drying or lyophilization, spray drying, spray freeze-drying, supercritical fluid drying, particle replication in nonwetting templates, and fluidized bed drying. Area covered In this review, we discuss drying technologies and their applications in the production of stable solid-state biopharmaceuticals, providing examples of commercially available products or clinical trial formulations. Alongside this, we also review how different analytical methods may be utilized in the evaluation of aerosol performance and powder characteristics of dried protein powders. Finally, we assess the protein integrity in terms of conformational and physicochemical stability and biological activity. Expert opinion With the aim of treating either infectious respiratory diseases or systemic disorders, inhaled biopharmaceuticals reduce both therapeutic dose and cost of therapy. Drying methods in the presence of optimized protein/stabilizer combinations, produce solid dosage forms of proteins with greater stability. A suitable drying method was chosen, and the process parameters were optimized based on the route of protein administration. With the ongoing trend of addressing deficiencies in biopharmaceutical production, developing new methods to replace conventional drying methods, and investigating novel excipients for more efficient stabilizing effects, these products have the potential to dominate the pharmaceutical industry in the future.
Drying Technologies for the Stability and Bioavailability of Biopharmaceuticals
Pharmaceutics, 2018
Solid dosage forms of biopharmaceuticals such as therapeutic proteins could provide enhanced bioavailability, improved storage stability, as well as expanded alternatives to parenteral administration. Although numerous drying methods have been used for preparing dried protein powders, choosing a suitable drying technique remains a challenge. In this review, the most frequent drying methods, such as freeze drying, spray drying, spray freeze drying, and supercritical fluid drying, for improving the stability and bioavailability of therapeutic proteins, are discussed. These technologies can prepare protein formulations for different applications as they produce particles with different sizes and morphologies. Proper drying methods are chosen, and the critical process parameters are optimized based on the proposed route of drug administration and the required pharmacokinetics. In an optimized drying procedure, the screening of formulations according to their protein properties is perfor...
The Secondary Drying and the Fate of Organic Solvents for Spray Dried Dispersion Drug Product
Pharmaceutical research, 2014
To understand the mechanisms of secondary drying of spray-dried dispersion (SDD) drug product and establish a model to describe the fate of organic solvents in such a product. The experimental approach includes characterization of the SDD particles, drying studies of SDD using an integrated weighing balance and mass spectrometer, and the subsequent generation of the drying curve. The theoretical approach includes the establishment of a Fickian diffusion model. The kinetics of solvent removal during secondary drying from the lab scale to a bench scale follows Fickian diffusion model. Excellent agreement is obtained between the experimental data and the prediction from the modeling. The diffusion process is dependent upon temperature. The key to a successful scale up of the secondary drying is to control the drying temperature. The fate of primary solvents including methanol and acetone, and their potential impurity such as benzene can be described by the Fickian diffusion model. A ma...