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(a) Spin-freezing of a vial along its longitudinal axis and (b) Spin-freeze-dried vials. Reprinted from (De Meyer et al., 2017) with permission from Elsevier.

(a) Spin-freezing of a vial along its longitudinal axis and (b) Spin-freeze-dried vials. Reprinted from (De Meyer et al., 2017) with permission from Elsevier.

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Article
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In the past two decades, biopharmaceuticals have been a breakthrough in improving the quality of lives of patients with various cancers, autoimmune, genetic disorders etc. With the growing demand of biopharmaceuticals, the need for reducing manufacturing costs is essential without compromising on the safety, quality, and efficacy of products. Batch...

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... Freeze-drying process, authors invented a novel continuous Freeze-drying process for unit doses (Corver, 2012;De Meyer et al., 2015). A major characteristic of this continuous Freeze-drying technology is the rotation of vials containing the liquid product of interest along their longitudinal axis, therefore, this is known as Spin-freeze-drying (Fig. ...

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... Proteins in solution are more prone to chemical and physical degradation processes which are hydrolytically driven [18]. They also require the cold chain which is a formidable logistical challenge that adds to the high costs of producing mAbs [19]. Thus, another benefit of formulating thermosensitive proteins into dry powders is the ease of transport and storage. ...
... In spray freeze drying, some product was lost likely due to the retention of residual feed solution in the syringe and feeding tube. Nevertheless, spray drying is a more established and popular drying technology than spray freeze drying for industrial scale production [19,52,53]. ...
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Objective The therapeutic options for severe asthma are limited, and the biological therapies are all parenterally administered. The purpose of this study was to formulate a monoclonal antibody that targets the receptor for IL-4, an interleukin implicated in the pathogenesis of severe asthma, into a dry powder intended for delivery via inhalation. Methods Dehydration was achieved using either spray drying or spray freeze drying, which exposes the thermolabile biomacromolecules to stresses such as shear and adverse temperatures. 2-hydroxypropyl-beta-cyclodextrin was incorporated into the formulation as protein stabiliser and aerosol performance enhancer. The powder formulations were characterised in terms of physical and aerodynamic properties, while the antibody was assessed with regard to its structural stability, antigen-binding ability, and in vitro biological activity after drying. Results The spray-freeze-dried formulations exhibited satisfactory aerosol performance, with emitted fraction exceeding 80% and fine particle fraction of around 50%. The aerosolisation of the spray-dried powders was hindered possibly by high residual moisture. Nevertheless, the antigen-binding ability and inhibitory potency were unaffected for the antibody in the selected spray-dried and spray-freeze-dried formulations, and the antibody was physically stable even after one-year storage at ambient conditions. Conclusions The findings of this study establish the feasibility of developing an inhaled dry powder formulation of an anti-IL-4R antibody using spray drying and spray freeze drying techniques with potential for the treatment of severe asthma.
... In contrast, spray drying is an enabling particle engineering technique, used to manufacture respirable particles of both small and large molecule active pharmaceutical ingredients (API) in a single-unit operation [7][8][9]. Spray drying as a pharmaceutical manufacturing technique has been reviewed extensively elsewhere [10,11]. Briefly, actives and excipients are co-dissolved in a volatile solvent and then atomized into droplets that are sprayed into a drying chamber. ...
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Spray drying is a particle engineering technique used to manufacture respirable pharmaceutical powders that are suitable for delivery to the deep lung. It is amenable to processing both small molecules and biologic actives, including proteins. In this work, a simultaneous spray-drying process, termed simul-spray, is described; the process involves two different active pharmaceutical ingredient (API) solutions that are simultaneously atomized through separate nozzles into a single-spray dryer. Collected by a single cyclone, simul-spray produces a uniform mixture of two different active particles in a single-unit operation. While combination therapies for dry powder inhalers containing milled small molecule API are commercially approved, limited options exist for preparing combination treatments that contain both small molecule APIs and biotherapeutic molecules. Simul-spray drying is also ideal for actives which cannot withstand a milling-based particle engineering process, or which require a high dose that is incompatible with a carrier-based formulation. Three combination case studies are demonstrated here, in which bevacizumab is paired with erlotinib, cisplatin, or paclitaxel in a dry powder inhaler formulation. These model systems were chosen for their potential relevance to the local treatment of lung cancer. The resulting formulations preserved the biologic activity of the antibody, achieved target drug concentration, and had aerosol properties suitable for pulmonary delivery.
Article
This study addressed the need for a flexible (personalizable) production of biologics, allowing their stabilization in the solid state and processing of small batch volumes. Therefore, inkjet printing into vials followed by a gentle vacuum drying step at ambient temperature was investigated by screening different formulations with a 22-full factorial design of experiments regarding printability. Human Serum Albumin (HSA) was used as a model protein in a wide range of concentrations (5 to 50 mg/ml), with (10 w/v%) and without the surfactant polysorbate80 (PS80). PS80 was identified to positively affect the formulations by increasing the Ohnesorge number and stabilizing the printing process. The dispensed volumes with a target dose of 0.5mg HSA were dried and analyzed concerning their residual moisture (RM) and protein aggregation. All investigated formulations showed an RM <10wt.% and no significant induced protein aggregation as confirmed by Size Exclusion Chromatography (< 2.5%) and Dynamic Light Scattering (Aggregation Index ≤ 2.5). Additionally, long-term printability and the available final dose after reconstitution were investigated for two optimized formulations. A promising formulation providing ∼93% of the targeted dose and a reconstitution time of 30s was identified.
Article
The inability of many biopharmaceutical formulations to retain their structure and integrity when in solution represents a major issue for their transport and storage, reducing their shelf-life and activity/stability. The ability to efficiently produce dried solid dosage forms of biopharmaceuticals such as proteins and nucleic acids allows for many improvements in the way in which these sensitive materials are stored, transported, and administered. While freeze-drying is an established drying method implemented in the biopharmaceutical industry with well-understood challenges, there has been a distinct lack of uptake in the development and usage of spray drying and supercritical fluid drying. These technologies typically provide distinct particles sizes and morphologies, introducing an additional route to improve the final product performance. This review focuses on the key aspects of various supercritical fluid methods reported in the literature to produce dried biopharmaceutical powders with enhanced stability compared to those produced by more conventional methods.