Abstract
The objective of this study was to examine the effects of formulation and process variables on particle size and other characteristics of a spray-dried model protein, bovine serum albumin (BSA), using a partial factorial design for experiments. Formulation variables tested include concentration and zinc:protein complexation ratio. Process variables explored were inlet temperature, liquid feed rate, drying air flow rate, and atomizing nitrogen pressure on a lab-scale spray dryer. Statistical data analysis was used to determine F ratios for each of the inputs, which provided a means of ranking the importance of variables relative to one another for each powder characteristic of interest. It was found that protein concentration and atomizing nitrogen pressure had the greatest effects on the particle size of the protein powder. For determining product yield, results showed that protein concentration was the critical variable. Finally, the outlet temperature was mostly influenced by inlet temperature and liquid feed rate. Mathematical models based on these input-output relationships were constructed; these models provide insight into some of the controllable variables of the spray-drying process.
Key Words: Bovine serum albumin (BSA), Particle size, Spray drying, outlet temperature, Yield
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References
- 1.Masters K. Spray Drying Handbook. New York, NY: John Wiley and Sons; 1991. [Google Scholar]
- 2.Broadhead J, Rouan Edmond SK, Hau I, Rhodes CT. The effect of process and formulation variables on the properties of spray-dried b-galactosidase. J Pharm Pharmacol. 1994;46:458–467. doi: 10.1111/j.2042-7158.1994.tb03828.x. [DOI] [PubMed] [Google Scholar]
- 3.Mumenthaler M, Hsu CC, Pearlman R. Feasibility study on spray drying protein pharmaceutic als. Recombinant human growth hormone and tissue-type plasminogen activator. Pharm Res. 1994;11:12–20. doi: 10.1023/A:1018929224005. [DOI] [PubMed] [Google Scholar]
- 4.Chan H-K, Clark A, Gonda I, Mumenthaler M, Hsu CC. Spray dried powders and powder blends of recombinant human deoxyribonuclease (rhDNase) for aerosol delivery. Pharm Res. 1997;14:431–437. doi: 10.1023/A:1012035113276. [DOI] [PubMed] [Google Scholar]
- 5.Maa Y-F, Nguyen P-A, Hsu SW. Spray-drying of airliquid interface sensitive recombinant human growth hormone. J Pharm Sci. 1998;87:152–159. doi: 10.1021/js970308x. [DOI] [PubMed] [Google Scholar]
- 6.Andya JD, Maa Y-F, Costantino HR, Nguyen P-A, Dasovich N, Sweeney TD, Hsu CC, Shire SJ. The effect of formulations excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody. Pharm Res. 1999;16:350–358. doi: 10.1023/A:1018805232453. [DOI] [PubMed] [Google Scholar]
- 7.Costantino HR, Firouzabadian L, Hogeland K, Wu C, Beganski C, Carrasquillo KG, Córdova M, Griebenow K, Zale SE, Tracy MA. Protein spray-freeze drying. Effect of atomization conditions on particle size and stability. Pharm Research. 2000;17:1374–1383. doi: 10.1023/A:1007570030368. [DOI] [PubMed] [Google Scholar]
- 8.Johnson OL, Jaworowicz W, Cleland JL, Bailey L, Charnis M, Duenas E, Wu C, Shepard D, Magil S, Last T, Jones AJS, Putney SD. The stabilization of human growth hormone into biodegradable microspheres. Pharm Res. 1997;14:730–735. doi: 10.1023/A:1012142204132. [DOI] [PubMed] [Google Scholar]
- 9.Vanbever R, Mintzes JD, Wang J, Nice J, Chen D, Batycky R, Langer R, Edwards DA. Formulation and physical characterization of large porous particles for inhalation. Pharm Res. 1999;16:1735–1742. doi: 10.1023/A:1018910200420. [DOI] [PubMed] [Google Scholar]
- 10.Maa Y-F, Costantino HR, Nguyen P-A, Hsu CC. The effect of operating and formulation variables on the morphology of spray-dried protein particles. Pharm Dev Technol. 1997;2(3):213–223. doi: 10.3109/10837459709031441. [DOI] [PubMed] [Google Scholar]