ALBERT — All Library Books, journals and Electronic Records Telegrafenberg

1

Electronic Resource

Protein Inhalation Powders: Spray Drying vs Spray Freeze Drying (1999)

Maa, Yuh-Fun ; Nguyen, Phuong-Anh ; Sweeney, Theresa ; [et al.]

Springer

Pharmaceutical research 16 (1999), S. 249-254

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: spray freeze drying ; spray drying ; dispersibility ; fine particle fraction ; liquid impingement ; cascade impaction ; aerodynamic particle size

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. Methods. Protein powders were characterized using particle size analysis, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffractometry, and specific surface area measurement. Aerosol performance of the powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger or an Anderson cascade impactor. Two recombinant therapeutic proteins currently used for treating respiratory tract-related diseases, deoxyribonuclase (rhDNase) and anti-IgE monoclonal antibody (anti-IgE MAb), were employed and formulated with different carbohydrate excipients. Results. Through the same atomization but the different drying process, spray drying (SD) produced small (∼3 μm), dense particles, but SFD resulted in large (∼8−10 μm), porous particles. The fine particle fraction (FPF) of the spray freeze-dried powder was significantly better than that of the spray-dried powder, attributed to better aerodynamic properties. Powders collected from different stages of the cascade impactor were characterized, which confirmed the concept of aerodynamic particle size. Protein formulation played a major role in affecting the powder's aerosol performance, especially for the carbohydrate excipient of a high crystallization tendency. Conclusions. Spray freeze drying, as opposed to spray drying, produced protein particles with light and porous characteristics, which offered powders with superior aerosol performance due to favorable aerodynamic properties.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018828425184

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

2

Electronic Resource

Effect of Spray Drying and Subsequent Processing Conditions on Residual Moisture Content and Physical/Biochemical Stability of Protein Inhalation Powders (1998)

Maa, Yuh-Fun ; Nguyen, Phuong-Anh ; Andya, James D. ; [et al.]

Springer

Pharmaceutical research 15 (1998), S. 768-775

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: spray drying ; residual moisture ; equilibrium moisture content ; relative humidity ; gravimetric moisture sorption isotherm ; protein aggregation

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. To understand the effect of spray drying and powder processing environments on the residual moisture content and aerosol performance of inhalation protein powders. Also, the long-term effect of storage conditions on the powder's physical and biochemical stability was presented. Methods. Excipient-free as well as mannitol-formulated powders of a humanized monoclonal antibody (anti-IgE) and recombinant human deoxyribonuclease (rhDNase) were prepared using a Buchi 190 model spray dryer. Residual moisture content and moisture uptake behavior of the powder were measured using thermal gravimetric analysis and gravimetric moisture sorption isotherm, respectively. Protein aggregation, the primary degradation product observed upon storage, was determined by size-exclusion HPLC. Aerosol performance of the dry powders was evaluated after blending with lactose carriers using a multi-stage liquid impinger (MSLI). Results. Spray-dried powders with a moisture level (~ 3%) equivalent to the freeze-dried materials could only be achieved using high-temperature spray-drying conditions, which were not favorable to large-male manufacturing, or subsequent vacuum drying. These dry powders would equilibrate with the subsequent processing and storage environments regardless of the manufacturing condition. As long as the relative humidity of air during processing and storage was lower than 50%, powders maintained their aerosol performance (fine particle fraction). However, powders stored under drier conditions exhibited better long-term protein biochemical stability. Conclusions. Manufacturing, powder processing, and storage environments affected powder's residual moisture level in a reversible fashion. Therefore, the storage condition determined powder's overall stability, but residual moisture had a greater impact on protein chemical stability than on powder physical stability.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1011983322594

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

3

Electronic Resource

The Effect of Formulation Excipients on Protein Stability and Aerosol Performance of Spray-Dried Powders of a Recombinant Humanized Anti-IgE Monoclonal Antibody1 (1999)

Andya, James D. ; Maa, Yuh-Fun ; Costantino, Henry R. ; [et al.]

Springer

Pharmaceutical research 16 (1999), S. 350-358

add to mindlist on the mindlist

Details

ISSN: 1573-904X

Keywords: aggregation ; glycation ; fine particle fraction ; protein formulation ; protein stability ; spray drying

Source: Springer Online Journal Archives 1860-2000

Topics: Chemistry and Pharmacology

Notes: Abstract Purpose. To study the effect of trehalose, lactose, and mannitol on the biochemical stability and aerosol performance of spray-dried powders of an anti-IgE humanized monoclonal antibody. Methods. Protein aggregation of spray-dried powders stored at various temperature and relative humidity conditions was assayed by size exclusion chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein glycation was determined by isoelectric focusing and affinity chromatography. Crystallization was examined by X-ray powder diffraction. Aerosol performance was assessed as the fine particle fraction (FPF) of the powders blended with coarse carrier lactose, and was determined using a multiple stage liquid impinger. Results. Soluble protein aggregation consisting of non-covalent and disulfide-linked covalent dimers and trimers occurred during storage. Aggregate was minimized by formulation with trehalose at or above a molar ratio in the range of 300:1 to 500:1 (excipient:protein). However, the powders were excessively cohesive and unsuitable for aerosol administration. Lactose had a similar stabilizing effect, and the powders exhibited acceptable aerosol performance, but protein glycation was observed during storage. The addition of mannitol also reduced aggregation, while maintaining the FPF, but only up to a molar ratio of 200:1. Further increased mannitol resulted in crystallization, which had a detrimental effect on protein stability and aerosol performance. Conclusions. Protein stability was improved by formulation with carbohydrate. However, a balance must be achieved between the addition of enough stabilizer to improve protein biochemical stability without compromising blended powder aerosol performance.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1018805232453

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

4

Electronic Resource

Membrane fouling in sterile filtration of recombinant human growth hormone (1996)

Maa, Yuh-Fun ; Hsu, Chung C.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 50 (1996), S. 319-328

add to mindlist on the mindlist

Details

ISSN: 0006-3592

Keywords: membrane fouling ; microfiltration ; sterile filtration ; quasi-elastic light scattering ; protein aggregation/adsorption ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: The most troublesome problem encountered during the sterile filtration of protein solutions is membrane fouling. This article presents our study on sterile filtration of a model protein, recombinant human growth hormone (rhGH). Scanning electron microscopy (SEM) analysis shows that 0.22-μm membranes, when used to filter the mannitol-formulated protein solution under a 0.35-bar transmembrane pressure, were plugged to a great extent. When zinc ions were added to induce aggregates, the fouling tendency of rhGH solutions increased with increasing amount and size of the aggregates, indicating that the aggregates present before filtration might be responsible for membrane fouling. However, repeated filtration of the same solution using a fresh filter each time cannot reduce membrane fouling, and all filtrates contain the same trace amount of hGH particulates as the prefiltered solution. Particulate size was determined to be between 0.03 and 0.15 μm by dynamic light scattering. Also, in view of the fact that protein formulations significantly affected the tendency of fouling with the same preexisting aggregates, it is likely that fouling was more attributed to the aggregation taking place in the filter pores during filtration (secondary aggregation) than to the aggregates present before filtration. Adding a surfactant to or increasing the pH of the protein solution improves the filtration, whereas increasing ionic strength slows down the filtration. This result suggests that the balance of the protein's interaction and electrostatic repulsion plays an important role in the protein's fouling tendency. Many factors might change the microenvironment in the pores and disturb this balance. Those considerations and the aggregation tendency of rhGH in the filter pores will be discussed in detail separately. © 1996 John Wiley & Sons, Inc.

Additional Material: 10 Ill.

Type of Medium: Electronic Resource

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

5

Electronic Resource

Protein denaturation by combined effect of shear and air-liquid interface (1997)

Maa, Yuh-Fun ; Hsu, Chung C.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 54 (1997), S. 503-512

add to mindlist on the mindlist

Details

ISSN: 0006-3592

Keywords: aggregation by air-liquid interface ; foaming ; rhDNase ; rhGH ; shear ; shear rate ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: The effect of shear alone on the aggregation of recombinant human growth hormone (rhGH) and recombinant human deoxyribonuclease (rhDNase) has been found to be insignificant. This study focused on the synergetic effect of shear and gas-liquid interface on these two model proteins. Two shearing systems, the concentric-cylinder shear device (CCSD) and the rotor/stator homogenizer, were used to generate high shear (〉 106) in aqueous solutions in the presence of air. High shear in the presence of an air-liquid interface had no major effect on rhDNase but caused rhGH to form noncovalent aggregates. rhGH aggregation was induced by the air-liquid interface and was found to increase with increasing protein concentration and the air-liquid interfacial area. The aggregation was irreversible and exhibited a first-order kinetics with respect to the protein concentration and air-liquid interfacial area. Shear and shear rate enhanced the interaction because of its continuous generation of new air-liquid interfaces. In the presence of a surfactant, aggregation could be delayed or prevented depending upon the type and the concentration of the surfactant. The effect of air-liquid interface on proteins at low shear was examined using a nitrogen bubbling method. We found that foaming is very detrimental to rhGH even though the shear involved is low. The use of anti-foaming materials could prevent rhGH aggregation during bubbling. The superior stability exhibited by rhDNase may be linked to the higher surface tension and lower foaming tendency of its aqueous solution. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 503-512, 1997.

Additional Material: 8 Ill.

Type of Medium: Electronic Resource

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

6

Electronic Resource

Spray-drying performance of a bench-top spray dryer for protein aerosol powder preparation (1998)

Maa, Yuh-Fun ; Nguyen, Phuong-Anh ; Sit, Kin ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 60 (1998), S. 301-309

add to mindlist on the mindlist

Details

ISSN: 0006-3592

Keywords: cyclone design and configuration ; receiving vessel ; spray drying ; system design ; production yield ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: The objective of this work was to improve a bench-top spray dryer's efficiency in both production recovery and throughput for preparing protein aerosol powders. A Büchi mini-spray dryer was used to prepare the powders of recombinant humanized anti-IgE antibody. The resulting powder's physical properties such as particle size, residual moisture, and morphology, along with its recovery and production rate was the basis of this development work. Mass balance suggests that approximately 10-20% of powder was lost in the exhaust air, consisting primarily of particles less than 2 μm. Also, significant loss (20-30%) occurred in the cyclone. Attempts were made to improve product recovery in the receiving vessel using dual-cyclone configurations, different cyclone designs, cyclones with anti-static treatment, and different receiver designs. System modifications such as replacing the original bag-filter unit with a vacuum system effectively reduced drying air flow resistance, allowing the protein to be dried at a lower inlet air temperature and the production scale to be increased. We concluded that the modified spray-drying system is advantageous over the original bench-top spray dryer. This improvement will be beneficial to early-stage research and development involving high-valued protein powders. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 301-309, 1998.

Additional Material: 8 Ill.

Type of Medium: Electronic Resource

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

7

Electronic Resource

Effect of high shear on proteins (1996)

Maa, Yuh-Fun ; Hsu, Chung C.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 51 (1996), S. 458-465

add to mindlist on the mindlist

Details

ISSN: 0006-3592

Keywords: concentric-cylinder shear device ; rotor/stator homogenization ; shear ; shear rate ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: Shear is present in almost all bioprocesses and high shear is associated with processes involving agitation and emulsification. The purpose of this study is to investigate the effect of high shear and high shear rate on proteins. Two concentric cylinder-based shear systems were used. One was a closed concentric-cylinder shear device (CCSD) and the other was a homogenizer with a rotor/stator assembly. Mathematical modeling of these systems allowed calculation of the shear rate and shear. The CCSD generated low shear rates (a few hundred s-1), whereas the homogenizer could generate very high shear rates (〉 105 s-1). High shear could be achieved in both systems by increasing the processing time. Recombinant human growth hormone (rhGH) and recombinant human deoxyribonuclease (rhDNase) were used as the model proteins in this study. It was found that neither high shear nor high shear rate had a significant effect on protein aggregation. However, a lower melting temperature and enthalpy were detected for highly sheared rhGH by using scanning microcalorimetry, presumably due to some changes in protein's conformation. Also, SDS-PAGE indicated the presence of low molecular-weight fragments, suggesting that peptide bond breakage occurred due to high shear. rhDNase was relatively more stable than rhGH under high shear. No conformational changes and protein fragments were observed. © 1996 John Wiley & Sons, Inc.

Additional Material: 9 Ill.

Type of Medium: Electronic Resource

Permalink

	Location	Call Number	Expected	Availability

Others were also interested in ...

Paper (German National Licenses)

8

Electronic Resource

Feasibility of protein spray coating using a fluid-bed Würster processor (1997)

Maa, Yuh-Fun ; Hsu, Chung C.

New York, NY [u.a.] : Wiley-Blackwell

Biotechnology and Bioengineering 53 (1997), S. 560-566

add to mindlist on the mindlist

Details

ISSN: 0006-3592

Keywords: aggregation ; Ca2+ ; fluid-bed ; microcalorimetry ; rhDNase ; spray coating ; Würster process ; Chemistry ; Biochemistry and Biotechnology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology

Notes: This article documents a feasibility study on coating fine powders with protein solutions using a Würster spray coater (GPCG-1 from Glatt Air Techniques, Ramsey, NJ). Spray coating was based on a fluid-bed process where fluidized microcarriers were coated inside the Würster column and dried in the fluidization chamber. Recombinant human deoxyribonuclease (rhDNase) was used as the model protein. Lactose powders of two different size ranges, 53-125 and 125-250 μm, were used as the model microcarrier. The amount of protein applied was varied to obtain coatings of varying thickness. The extent of rhDNase loading determined experimentally was found to be consistent with the theoretical value and was also confirmed visually by scanning electron microscopy. The coating showed a strong integrity after being subjected to mechanical force. However, the protein suffered serious aggregation during coating, most likely due to the thermal stress of the process. Aggregation was significantly reduced when rhDNase was formulated with calcium ions, consistent with the observation that Ca2+ thermally stabilized the protein (as determined by scanning microcalorimetry) in aqueous solution. Thus, our study demonstrates that spray coating, particularly when used in conjunction with rational stabilization strategies, is a feasible alternative to other methods of preparing dried pharmaceutical proteins. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 560-566, 1997.

Additional Material: 6 Ill.

Type of Medium: Electronic Resource

Permalink