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Pharmaceutical Freeze Drying and Spray Drying, Volume II

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (20 January 2024) | Viewed by 10744

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Prof. Dr. Holger Grohganz

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Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark
Interests: freeze-drying and spray-drying; co-amorphous systems; process analytical technology and quality by design; peptides and proteins in pharmaceutical formulations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

With the increasing importance of biopharmaceuticals and their frequent inherent instability in the presence of water, pharmaceutical scientists have to consider the preparation of a dry formulation in order for the product to be safe and stable. For the gentle removal of solvent, freeze-drying and spray-drying are two commonly applied unit operations. Although both processes are long-established in pharmaceutical and other industries, actual product development is still often based on tradition or trial-and-error approaches, rather than on a conscious and rational design.

In the light of quality-by-design, a more thorough understanding of the interplay between the active ingredient and the critical formulation and process parameters is necessary. Understanding a system all the way—from its molecular interactions to the intermediate and bulk properties and the final dosage form—will ensure the highest quality.

This Special Issue serves to highlight the most recent developments and findings in the understanding of both freeze-drying and spray-drying.

Prof. Dr. Holger Grohganz
Guest Editor

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Keywords

solid state characterization
advanced biophysical characterization
process modelling
molecular interactions
process design
formulation optimization
PAT applications

Published Papers (5 papers)

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Research

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16 pages, 2785 KiB

Open AccessArticle

Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations

by Nicole Härdter, Raimund Geidobler, Ingo Presser and Gerhard Winter

Pharmaceutics 2023, 15(12), 2783; https://doi.org/10.3390/pharmaceutics15122783 - 15 Dec 2023

Viewed by 833

Abstract

Microwave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal antibody (mAb) formulations remains unclear. In this study, we systematically examined the effect of protein concentration in MFD and assessed protein stability following MFD, CFD, and subsequent storage using seven protein formulations with various stabilizers and concentrations. We demonstrated that microwaves directly interact with the active pharmaceutical ingredient (API), leading to decreased physical stability, specifically aggregation, in high-concentration antibody formulations. Furthermore, typically used sugar:protein ratios from CFD were insufficient for stabilizing mAbs when applying microwaves. We identified the intermediate drying phase as the most critical for particle formation, and cooling the samples provided some protection for the mAb. Our findings suggest that MFD technology may not be universally applicable to formulations well tested in CFD and could be particularly beneficial for formulations with low API concentrations requiring substantial amounts of glass-forming excipients, such as vaccines and RNA-based products. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying, Volume II)

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15 pages, 5801 KiB

Open AccessArticle

Preparation of Co-Amorphous Levofloxacin Systems for Pulmonary Application

by Aljoscha Gabelmann, Claus-Michael Lehr and Holger Grohganz

Pharmaceutics 2023, 15(6), 1574; https://doi.org/10.3390/pharmaceutics15061574 - 23 May 2023

Cited by 4 | Viewed by 1237

Abstract

Addressing antimicrobial resistance requires new approaches in various disciplines of pharmaceutical sciences. The fluoroquinolone levofloxacin (LEV) plays an important role in the therapy of lung infections. However, its effectiveness is limited by its severe side effects involving tendinopathy, muscle weakness and psychiatric disturbance. Therefore, there is a need for the development of an effective formulation of LEV with reduced systemic drug concentrations, thereby also reducing the consumption and excretion of antibiotics or metabolites. This study aimed for the development of a pulmonary-applicable LEV formulation. Co-amorphous LEV-L-arginine (ARG) particles were prepared by spray drying and characterised by scanning electron microscopy, modulated differential scanning calorimetry, X-ray powder diffraction, Fourier-transform infrared spectroscopy and next generation impactor analysis. Co-amorphous LEV-ARG salts were produced independently of varying process parameters. The use of 30% (v/v) ethanol as a solvent led to better aerodynamic properties compared to an aqueous solution. With a mass median aerodynamic diameter of just over 2 µm, a fine particle fraction of over 50% and an emitted dose of over 95%, the product was deemed suitable for a pulmonary application. The created process was robust towards the influence of temperature and feed rate, as changing these parameters did not have a significant influence on the critical quality attributes, indicating the feasibility of producing pulmonary-applicable co-amorphous particles for sustainable antibiotic therapy. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying, Volume II)

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20 pages, 3200 KiB

Open AccessArticle

Particle Engineering by Nano Spray Drying: Optimization of Process Parameters with Hydroethanolic versus Aqueous Solutions

by Khaled Almansour, Raisuddin Ali, Fawaz Alheibshy, Tariq J. Almutairi, Rakan F. Alshammari, Nasser Alhajj, Cordin Arpagaus and Mustafa M.A. Elsayed

Pharmaceutics 2022, 14(4), 800; https://doi.org/10.3390/pharmaceutics14040800 - 06 Apr 2022

Cited by 17 | Viewed by 4211

Abstract

Nano spray drying has emerged as an outstanding platform for engineering micro- and nanoparticles, with growing applications in various areas of drug delivery. As a new technology involving distinct technical design, parameters of the nano spray drying process are not fully elucidated. In a quality-by-design approach, the aim of the current study was to gain thorough understanding of critical determinants of product characteristics in the Büchi Nano Spray Dryer B-90. Following a factorial experimental design, a series of spray drying experiments were conducted to gain new insights into the influences of the inlet temperature, the spray solvent, and the solute concentration in the spray solution on the yield, the moisture content, and the particle size of the nano spray-dried powder material. Special consideration was given to the potential of using hydroethanolic in comparison with aqueous solvent systems and to particle engineering for pulmonary drug delivery. Lactose and mannitol, widely used as excipients in dry powder inhalation formulations, were used as model materials. Lactose and mannitol are known to spray dry in amorphous and crystalline forms, respectively. The yields of spray drying of lactose and mannitol amounted generally to 71.1 ± 6.6% w/w and 66.1 ± 3.5% w/w, respectively. The spray-dried materials exhibited generally a number-weighted median particle diameter of 1.6 ± 0.2 μm and a volume-weighted median particle diameter of 5.1 ± 1.0 μm. A detailed analysis of the results improved understanding of the interplay between process parameters in the Nano Spray Dryer. The results demonstrate that optimization of spray generation is the key to yield optimization. On the other hand, particle size is determined by the spray mesh pore size and the spray solution degree of saturation. Selection of an appropriate spray solvent and using spray solution additives could optimize spray flow. In parallel, the spray solvent and the solute concentration in the spray solution determine the degree of saturation. Guidance on optimization of particle engineering by nano spray drying is provided. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying, Volume II)

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15 pages, 4826 KiB

Open AccessArticle

Thermodynamic Balance vs. Computational Fluid Dynamics Approach for the Outlet Temperature Estimation of a Benchtop Spray Dryer

by Andrea Milanesi, Francesco Rizzuto, Maurizio Rinaldi, Andrea Foglio Bonda, Lorena Segale and Lorella Giovannelli

Pharmaceutics 2022, 14(2), 296; https://doi.org/10.3390/pharmaceutics14020296 - 27 Jan 2022

Cited by 1 | Viewed by 2307

Abstract

The use of design space (DS) is a key milestone in the quality by design (QbD) of pharmaceutical processes. It should be considered from early laboratory development to industrial production, in order to support scientists with making decisions at each step of the product’s development life. Presently, there are no available data or methodologies for developing models for the implementation of design space (DS) on laboratory-scale spray dryers. Therefore, in this work, a comparison between two different modeling approaches, thermodynamics and computational fluid dynamics (CFD), to a laboratory spray dryer model have been evaluated. The models computed the outlet temperature (

T_{out}

) of the process with a new modeling strategy that includes machine learning to improve the model prediction. The model metrics calculated indicate how the thermodynamic model fits

T_{out}

data better than CFD; indeed, the error of the CFD model increases towards higher values of

T_{out}

and feed rate (

F R

), with a final mean absolute error of 10.43 K, compared to the 1.74 K error of the thermodynamic model. Successively, a DS of the studied spray dryer equipment has been implemented, showing how

T_{out}

is strongly affected by

F R

variation, which accounts for about 40 times more than the gas flow rate (

G_{in}

) in the DS. The thermodynamic model, combined with the machine learning approach here proposed, could be used as a valid tool in the QbD development of spray-dried pharmaceutical products, starting from their early laboratory stages, replacing traditional trial-and-error methodologies, preventing process errors, and helping scientists with the following scale-up. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying, Volume II)

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Review

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18 pages, 6401 KiB

Open AccessReview

Modification of the Physicochemical Properties of Active Pharmaceutical Ingredients via Lyophilization

by Amir Taldaev, Denis I. Pankov, Roman P. Terekhov, Anastasia K. Zhevlakova and Irina A. Selivanova

Pharmaceutics 2023, 15(11), 2607; https://doi.org/10.3390/pharmaceutics15112607 - 09 Nov 2023

Viewed by 1289

Abstract

Bioavailability is an important biopharmaceutical characteristic of active pharmaceutical ingredients (APIs) that is often correlated with their solubility in water. One of the methods of increasing solubility is freeze drying (lyophilization). The article provides a systematic review of studies published from 2012 to 2022 aimed at optimizing the properties of active pharmaceutical ingredients by freeze drying. This review was carried out in accordance with the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). In general, 141 modifications of 36 APIs attributed to 12 pharmacological groups were reported in selected publications. To characterize the products of phase modification after lyophilization, a complex of analytical methods was used, including microscopic, thermal, X-ray, and spectral approaches. Solubility and pharmacokinetic parameters were assessed. There is a tendency to increase solubility due to the amorphization of APIs during lyophilization. Thus, the alcohol lyophilizate of dihydroquercetin is “soluble” in water compared to the initial substance belonging to the category “very poorly soluble”. Based on the analysis of the literature, it can be argued that lyophilization is a promising method for optimizing the properties of APIs. Full article

(This article belongs to the Special Issue Pharmaceutical Freeze Drying and Spray Drying, Volume II)

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