Development of spray-dried corn and tapioca starch microparticles for protein delivery


  • Chirasak Kusonwiriyawong College of Pharmacy, Rangsit University, Patumthani 12000, Thailand


biodegradable, corn starch, microparticles, protein, protein delivery, spray-drying, tapioca starch


Protein drugs are susceptible to physical and chemical instabilities at every step of their product life cycle.  Encapsulating the drugs within biocompatible and biodegradable microparticles made of starch is likely an efficient approach to overcome such limitations.  This study aimed to develop corn and tapioca starch microparticles for the delivery of protein drugs using the Mini Spray Dryer B-290 (Büchi Labortechnik AG).  Effects of processing conditions, including inlet drying air temperature (100 to 170oC), liquid feed rate (1.9 to 7.0 g/min), atomizing air volumetric flow rate (240 to 740 L/h), aspirator vacuum (-30 to -48 mbar), and formulation parameters, namely type (corn and tapioca starch) and concentration of starch paste (2 to 8% w/w), on their physicochemical properties were characterized.  Particle size and morphology were examined by light diffraction and scanning electron microscopy, respectively.  The microparticle size ranged from 10.5 to 30.9 µm, depending mainly on the atomizing air volumetric flow rate and the liquid feed concentration.  All microparticles showed a distorted surface.  Product collection efficiency was as low as 6.0 to 34.5%.  Bovine serum albumin (BSA), as a model protein drug, was incorporated into the microparticles at levels of 1.0 to 5.0%.  The encapsulated protein content was determined by bicinchoninic acid assay.  Actual protein loading and entrapment efficiency ranged from 1.0 to 5.2% and 94.3 to 124.9%, respectively.  The protein-loaded microparticles were smaller in size than their corresponding blank microparticles, possibly due to the ease of feed atomization.  The integrity of the encapsulated protein was studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.  It was evident that the integrity of entrapped protein was completely retained.  Starch microparticles for protein delivery were efficiently developed by the spray-drying process.


Amaro, M. I., Tajber, L., Corrigan, O. I., & Healy, A. M. (2011). Optimization of spray drying process conditions for sugar nanoporous microparticles (NPMPs) intended for inhalation. International Journal of Pharmaceutics, 421(1), 99-109. DOI:

Ameri, M., & Maa, Y. F. (2006). Spray drying of biopharmaceuticals: Stability and process considerations. Drying Technology, 24(6), 763-768. DOI:

Bajpai, A. K., & Bhanu, S. (2007). Dynamics of controlled release of heparin from swellable crosslinked starch microspheres. Journal of Materials Science: Materials in Medicine, 18, 1613-1621. DOI:

Bazaria, B., & Kumar, P. (2018). Optimization of spray drying parameters for beetroot juice powder using response surface methogology (RSM). Journal of the Saudi Society of Agricultural Sciences, 17(4), 408-415. DOI:

Biswas, N., & Sahoo, R. K. (2016). Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of metoprolol tartrate. International Journal of Biological Macromolecules, 83, 61-70. DOI:

Chang, L. S., Tan, Y. T., & Pui, L. P. (2020). Production of spray-dried enzyme-liquefied papaya (Carica papaya L.) powder. Brazilian Journal of Food Technology, 23, e2019181. DOI:

Desai, K. G. H. (2005). Preparation and characterization of high-amylose corn starch/pectin blend microparticles: A technical note. AAPS PhramSciTech, 6(2), E202-E208, article 30. DOI:

Elfstrand, L., Eliasson, A. C., Jönsson, M., Reslow, M., & Wahlgren, M. (2006). From starch to starch microspheres: Factors controlling the microsphere quality. Starch/Stärke, 58, 381-390. DOI:

Elfstrand, L., Eliasson, A. C., & Wahlgren, M. (2009). The effect of starch material, encapsulated protein and production conditions on the protein release from starch microspheres. Journal of Pharmaceutical Sciences, 98(10), 3802-3815. DOI:

Emami, F., Vatanara, A., Park, E. J., & Na, D. H. (2018). Drying technology for the stability and bioavailability of biopharmaceuticals. Pharmaceutics, 10(3), 131. DOI:

Fang, Y. Y., Wang, L. J., Li, D., Li, B. Z., Bhandari, B., Chen, X. D., & Mao, Z. H. (2008). Preparation of crosslinked starch microspheres and their drug loading and releasing properties. Carbohydrate Polymers, 74(3), 379-384. DOI:

Focaroli, S., Mah, P. T., Hastedt, J. E., Gitlin, I., Oscarson, S., Fahy, J. V., & Healy, A. M. (2019). A design of experiment (DoE) approach to optimize spray drying process conditions for the production of trehalose/leucine formulation with application in pulmonary delivery. International Journal of Pharmaceutics, 562, 228-240. DOI:

George, A., Shah, P. A., & Shrivastav, P. S. (2019). Natural biodegradable polymers based nano-formulations for drug delivery: A review. International Journal of Pharmaceutics, 561, 244-264. DOI:

Geraldes, D. C., Beraldo-de-Araújo, V. L., Pardo, B. O. P., Pessoa Junior, A., Stephano, M. A., & de Oliveira-Nascimento, L. (2020). Protein drug delivery: Current dosage form profile and formulation strategies. Journal of Drug Targeting, 28(4), 339-355. DOI:

Gikanga, B., Turok, R., Hui, A., Bowen, M., Stauch, O. B., & Maa, Y. F. (2015). Manufacturing of high-concentration monoclonal antibody formulations via spray drying – the road to manufacturing scale. PDA Journal of Pharmaceutical Science and Technology, 69(1), 59-73. DOI:

Gong, Z., Zhang, M., Mujumdar, A. S., & Sun, J. (2008). Spray drying and agglomeration of instant barberry powder. Drying Technology, 26(1), 116-121. DOI:

Goula, A. M., & Adamopoulos, K. G. (2004). Spray drying of tomato pulp: Effect of feed concentration. Drying Technology, 22(10), 2309-2330. DOI: 10.1081/LDRT-200040007

Griebenow, K., & Klibanov, A. M. (1995). Lyophilization-induced reversible changes in the secondary structure of proteins. Proceedings of the National Academy of Sciences of the United States of America, 92(24), 10969-10976. DOI:

Häusler, O. (2012). Starch. Handbook of Pharmaceutical Excipients (pp. 784-790). London, UK: Pharmaceutical Press.

He, P., Davis, S. S., & Illum, L. (1999). Chitosan microparticles prepared by spray drying. International Journal of Pharmaceutics, 187(1), 53-65. DOI:

Janaswamy, S. (2014). Encapsulation altered starch digestion: Toward developing starch-based delivery systems. Carbohydrate Polymers, 101, 600-605. DOI:

Kaushik, K., Sharma, R. B., & Agarwal, S. (2016). Natural polymers and their applications. International Journal of Pharmaceutical Sciences Review and Research, 37(2), 30-36.

Kusonwiriyawong, C., Pichayakorn, W., Lipipun, V., & Ritthidej, G. C. (2009). Retained integrity of protein encapsulated in spray-dried chitosan microparticles. Journal of Microencapsulation, 26(2), 111-121. DOI:

Lengyel, M., Kállai-Szabó, N., Antal, V., Laki, A. J., & Antal, I. (2019). Microparticles, microspheres, and microcapsules for advanced drug delivery. Scientia Pharmaceutica, 87, article 20. DOI:

Li, B. Z., Wang, L. J., Li, D., Bhandari, B., Li, S. J., Lan, Y., Chen, X. D., & Mao, Z. H. (2009a). Fabrication of starch-based microparticles by an emulsification crosslinking method. Journal of Food Engineering, 92(3), 250-254. DOI:

Li, B. Z., Wang, L. J., Li, D., Chiu, Y. L., Zhang, Z. J., Shi, J., Chen, X. D., & Mao, Z. H. (2009b). Physical properties and loading capacity of starch-based microparticles crosslinked with trisodium trimetraphosphate. Journal of Food Engineering, 92(3), 255-260. DOI:

Li, B. Z., Wang, L. J., Li, D., Adhikari, B., & Mao, Z. H. (2012). Preparation and characterization of crosslinked starch microspheres using a two-stage water-in-water emulsion method. Carbohydrate Polymers, 88(3), 912-916. DOI:

Liu, C. S., Desai, K. G. H., Meng, X. H., & Chen, X. G. (2007). Sweet potato starch microparticles as controlled drug release carriers: Preparation and in vitro drug release. Drying Technology, 25(4), 689-693. DOI:

Liu, W., Wu, W. D., Selomulya, C., & Chen, X. D. (2011). Uniform chitosan microparticles prepared by a novel spray-drying technique. International Journal of Chemical Engineering, Article ID 267218. DOI:

Maa, Y. F., & Hsu, C. C. (1997). Protein denaturation by combined effect of shear and air-liquid interface. Biotechnology and Bioengineering, 54(6), 503-512. DOI:<503::AID-BIT1>3.0.CO;2-N

Maa, Y. F., Nguyen, P. T., & Hsu, S. W. (1998). Spray-drying of air-liquid interface sensitive recombinant human growth hormone. Journal of Pharmaceutical Sciences, 87(2), 152-159. DOI:

Maa, Y. F., Nguyen, P. T., Sit, K., & Hsu, S. W. (1998). Spray-drying performance of a bench-top spray dryer for protein aerosol powder preparation. Biotechnology and Bioengineering, 60(3), 301-309. DOI:<301::AID-BIT5>3.0.CO;2-L

Maury, M., Murphy, K., Kumar, S., Shi, L., & Lee, G. (2005). Effects of process variables on the powder yield of spray-dried trehalose on a laboratory spray-dryer. European Journal of Pharmaceutics and Biopharmaceutics, 59, 565-573. DOI:

Moreno-Mendieta, S. A., Guillén, D., Espitia, C., Hernández-Pando, R., Sanchez, S., & Rodriguez-Sanoja, R. (2014). A novel antigen-carrier system: The Mycobacterium tuberculosis Acr protein carried by raw starch microparticles. International Journal of Pharmaceutics, 474(1-2), 241-248. DOI:

Mumenthaler, M., Hsu, C. C., & Pearlman, R. (1994). Feasibility study on spray-drying protein pharmaceuticals: Recombinant human growth hormone and tissue-type plasminogen activator. Pharmaceutical Research, 11, 12-20. DOI:

Mundargi, R. C., Shelke, N. B., Rokhade, A. P., Patil, S. A., & Aminabhavi, T. M. (2008). Formulation and in-vitro evaluation of novel starch-based tableted microspheres for controlled release of ampicillin. Carbohydrate Polymers, 71, 42-53. DOI:

O’Riordan, K., Andrews, D., Buckle, K., & Conway, P. (2001). Evaluation of microencapsulation of a Bifidobacterium strain with starch as an approach to prolonging viability during storage. Journal of Applied Microbiology, 91, 1059-1066. DOI:

Phromsopha, T., Srihanam, P., & Baimark, Y. (2012). Preparation of cross-linked starch microparticles by water-in-oil emulsion solvent diffusion method for use as drug delivery carriers. Asian Journal of Chemistry, 24(1), 285-287.

Prestrelski, S., Tedeschi, N., Arakawa, T., & Carpenter, J. F. (1993). Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers. Biophysical Journal, 65, 661-671. DOI:

Queiroz, V. M., Kling, I. C. S., Eltom, A. E., Archanjo, B. S., Prado, M., & Simao, R. A. (2020). Corn starch films as a long-term drug delivery system for chlorhexidine gluconate. Materials Science & Engineering C, 112, 110852. DOI: 10.1016/j.msec.2020.110852

Rapp, B. E. (2017). Microfluidics: Modelling, mechanics and mathematics. Oxford, UK: Elsevier.

Soltani, E. K., Bahri, Z. E., Djerboua, F., & Baitiche, M. (2014). Controlled release of niflumic acid from native, pregelatinized and crosslinked corn starches matrix tablets. Journal of Materials and Environmental Science, 5(6), 1839-1846.

Song, R., Murphy, M., Li, C., Ting, K., Soo, C., & Zheng, Z. (2018). Current development of biodegradable polymeric materials for biomedical applications. Drug Design, Development and Therapy, 12, 3117-3145. DOI:

Ståhl, K., Claesson, M., Lilliehorn, P., Lindén, H., & Bäckström, K. (2002). The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. International Journal of Pharmaceutics, 233(1-2), 227-237. DOI:

Sukaraseranee, W., Watcharamaisakul, S., Golman, B., & Suwanprateeb, J. (2017). Effect of process parameters on characteristics of spray-dried hydroxyapatite granules. Key Engineering Materials, 728, 341-346. DOI:

Telang, A. M., & Thorat, B. N. (2010). Optimization of process parameters for spray drying of fermented soy milk. Drying Technology, 28, 1445-1456. DOI:

Thirugnanasambandham, K., & Sivakumar, V. (2017). Influence of process conditions on the physicochemical properties of pomegranate juice in spray drying process: Modelling and optimization. Journal of the Saudi Society of Agricultural Sciences, 16(4), 358-366. DOI:

Tzannis, S. T., & Prestrelski, S. J. (1999). Activity-stability considerations of trypsinogen during spray drying: Effects of sucrose. Journal of Pharmaceutical Sciences, 88(3), 351-359. DOI:

Vehring, R. (2008). Pharmaceutical particle engineering via spray drying. Pharmaceutical Research, 25(5), 999-1022. DOI:

Walsh, G. (2003). Biopharmaceuticals: Biochemistry and Biotechnology. West Sussex, England: John Wiley & Sons.

Wang, W., Dufour, C., & Zhou, W. (2015). Impacts of spray-drying conditions on the physicochemical properties of soy sauce powders using maltodextrin as auxiliary drying carrier. CyTA – Journal of Food, 13(4), 548-555. DOI:

Wannaphatchaiyong, S., Heng, P. W. S., Suksaeree, J., Boonme, P., & Pichayakorn, W. (2019). Lidocaine loaded gelatin/gelatinized tapioca starch films for buccal delivery and the irritancy evaluation using chick chorioallantoic membrane. Saudi Pharmaceutical Journal, 27(8), 1085-1095.

Wei, Y., Huang, Y. H., Cheng, K. C., & Song, Y. L. (2020). Investigations of the influences of processing conditions on the properties of spray-dried chitosan-tripolyphosphate particles loaded with theophylline. Scientific Reports, 10(1), 1155. DOI:

Witschi, C., & Mrsny, R. J. (1999). In vitro evaluation of microparticles and polymer gels for use as nasal platforms for protein delivery. Pharmaceutical Research, 16(3), 382-390. DOI:

Wong, C. Y., Al-Salami, H., & Dass, C. R. (2018). Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin. International Journal of Pharmaceutics, 537, 223-244. DOI:

Yang, Y., Chen, Q., Lin, J., Cai, Z., Liao, G., Wang, K., Bai, L., Zhao, P., & Yu, Z. (2019). Recent advance in polymer based microspheric systems for controlled protein and peptide delivery. Current Medicinal Chemistry, 26(13), 2285-2296. DOI: 10.2174/0929867326666190409130207

Zhu, C., Shoji, Y., McCray, S., Burke, M., Hartman, C. E., Chichester, J. A., Breit, J., Yusibov, V., Chen, D., & Lai, M. (2014). Stabilization of HACI influenza vaccine by spray drying: Formulation development and process scale-up. Pharmaceutical Research, 31, 3006-3018. DOI:

Zier, K. I., Schultze, W., & Leopold, C. S. (2018). Factors influencing the properties and the stability of spray-dried Sennae fructus extracts. Drug Development and Industrial Pharmacy, 44(10), 1659-1667. DOI:

Zimmerman, I. (1997). Possibilities and limitations of laser light scattering techniques for particle size analysis. In R.H. Muller, W. Mehnert, & G.E. Hildebrand (Eds.). Particle and surface characterization methods (pp. 19-26). Stuttgart, Germany: Medpharm




How to Cite

Chirasak Kusonwiriyawong. (2023). Development of spray-dried corn and tapioca starch microparticles for protein delivery. Journal of Current Science and Technology, 11(3), 375–391. Retrieved from



Research Article