PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTES OF TREHALOSE AND INULIN AS STABILIZER

Authors

  • CYNTHIA MARISCA MUNTU Department of Pharmaceutics and Pharmaceutical Technology Development, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
  • SILVIA SURINI Department of Pharmaceutics and Pharmaceutical Technology Development, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia
  • CHRISTINA AVANTI Department of Pharmaceutics, Faculty of Pharmacy, Universitas Surabaya, Surabaya 60293, East Java, Indonesia
  • HAYUN Laboratory of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, Universitas Indonesia, Depok 16424, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2021.v13s4.43823

Keywords:

Insulin, Dry powder, Trehalose, Inulin, Preliminary study, Critical process parameters, Critical material attribute, Formulation, SFD

Abstract

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and the optimal ratio of trehalose and inulin as critical material attributes (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method.

Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula.

Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5%, and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively.

Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no delay in the SFD process and when the FD is in operation, it should not be interrupted until the powder is dry. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1.

Downloads

Download data is not yet available.

References

Saxenian H. Immunization financing: a resource guide for advocates, policy-makers, and program managers. Washington, DC: Resource Guide by Results for Development Institute; 2017.

Lai MC, Topp EM. Solid-state chemical stability of proteins and peptides. J Pharm Sci. 1999;88(5):489-500. doi: 10.1021/js980374e, PMID 10229638.

Wang W. Lyophilization and development of solid protein pharmaceuticals. Int J Pharm. 2000;203(1-2):1-60. doi: 10.1016/s0378-5173(00)00423-3, PMID 10967427.

Carpenter JF, Pikal MJ, Chang BS, Randolph TW. Rational design of stable lyophilized protein formulations: some practical advice. Pharm Res. 1997;14(8):969-75. doi: 10.1023/a:1012180707283, PMID 9279875.

Jiskoot W, Randolph TW, Volkin DB, Middaugh CR, Schöneich C, Winter G, Friess W, Crommelin DJ, Carpenter JF. Protein instability and immunogenicity: roadblocks to clinical application of injectable protein delivery systems for sustained release. J Pharm Sci. 2012;101(3):946-54. doi: 10.1002/jps.23018, PMID 22170395.

Hinrichs WLJ, Prinsen MG, Frijlink HW. Inulin glasses for the stabilization of therapeutic proteins. Int J Pharm. 2001;215(1-2):163-74. doi: 10.1016/s0378-5173(00)00677-3, PMID 11250102.

Mensink MA, Van Bockstal PJ, Pieters S, De Meyer L, Frijlink HW, van der Voort Maarschalk K, Hinrichs WLJ, De Beer T. In-line near infrared spectroscopy during freeze-drying as a tool to measure efficiency of hydrogen bond formation between protein and sugar, predictive of protein storage stability. Int J Pharm. 2015;496(2):792-800. doi: 10.1016/j.ijpharm.2015.11.030, PMID 26608621.

Tonnis WF, Mensink MA, de Jager A, van der Voort Maarschalk K, Frijlink HW, Hinrichs WLJ. Size and molecular flexibility of sugars determine the storage stability of freeze-dried proteins. Mol Pharm. 2015;12(3):684-94. doi: 10.1021/mp500423z, PMID 25581526.

Grasmeijer N, Stankovic M, de Waard H, Frijlink HW, Hinrichs WLJ. Unraveling protein stabilization mechanisms: vitrification and water replacement in a glass transition temperature controlled system. Biochim Biophys Acta. 2013;1834(4):763-9. doi: 10.1016/j.bbapap.2013.01.020. PMID 23360765.

Rodriguez Furlan LT, Lecot J, Perez Padilla A, Campderros ME, Zaritzky N. Effect of saccharides on glass transition temperatures of frozen and freeze dried bovine plasma protein. J Food Eng. 2011;106(1):74-9. doi: 10.1016/j.jfoodeng.2011.04.010.

Mensink MA, Frijlink HW, van der Voort Maarschalk KV, Hinrichs WLJ. How sugars protect proteins in the solid state and during drying. Eur J Pharm Biopharm. 2017;114:288-95. doi: 10.1016/j.ejpb.2017.01.024.

Allison SD, Chang B, Randolph TW, Carpenter JF. Hydrogen bonding between sugar and protein is responsible for inhibition of dehydration-induced protein unfolding. Arch Biochem Biophys. 1999;365(2):289-98. doi: 10.1006/abbi.1999.1175, PMID 10328824.

Teekamp N, Tian Y, Visser JC, Olinga P, Frijlink HW, Woerdenbag HJ, Hinrichs WLJ. Addition of pullulan to trehalose glasses improves the stability of β-galactosidase at high moisture conditions. Carbohydr Polym. 2017;176:374-80. doi: 10.1016/j.carbpol.2017.08.084, PMID 28927620.

Hinrichs WLJ. Specialty products I: biopharmaceuticals; 2017.

Ishwarya SP, Anandharamakrishnan C, Stapley AGF. Spray-freeze-drying: A novel process for the drying of foods and bioproducts. Trends Food Sci Technol. 2015;41(2):161-81. doi: 10.1016/j.tifs.2014.10.008.

Eggerstedt SN, Dietzel M, Sommerfeld M, Suverkrup R, Lamprecht A. Protein spheres prepared by drop jet freeze drying. Int J Pharm. 2012;438(1-2):160-6. doi: 10.1016/j.ijpharm.2012.08.035, PMID 22960322.

Pouya MA, Daneshmand B, Aghababaie S, Faghihi H, Vatanara A. Spray-freeze drying: a suitable method for aerosol delivery of antibodies in the presence of trehalose and cyclodextrins. AAPS PharmSciTech. 2018;19(5):2247-54. doi: 10.1208/s12249-018-1023-2, PMID 29740758.

Surini S, Akiyama H, Morishita M, Nagai T, Takayama K. Release phenomena of insulin from an implantable device composed of a polyion complex of chitosan and sodium hyaluronate. J Control Release. 2003;90(3):291-301. doi: 10.1016/s0168-3659(03)00196-2, PMID 12880696.

Xie T, Taylor LS. Effect of temperature and moisture on the physical stability of binary and ternary amorphous solid dispersions of celecoxib. J Pharm Sci. 2017;106(1):100-10. doi: 10.1016/j.xphs.2016.06.017, PMID 27476771.

Xi J, Yuan JE, Alshaiba M, Cheng D, Firlit Z, Johnson A, Nolan A, Su WC. Design and testing of electric-guided delivery of charged particles to the olfactory region: experimental and numerical studies. Curr Drug Deliv. 2016;13(2):265-74. doi: 10.2174/1567201812666150909093050, PMID 26362143.

Cheng YS, Holmes TD, Gao J, Guilmette RA, Li S, Surakitbanharn Y, Rowlings C. Characterization of nasal spray pumps and deposition pattern in a replica of the human nasal airway. J Aerosol Med. 2001;14(2):267-80. doi: 10.1089/08942680152484199, PMID 11681658.

Kundoor V, Dalby RN. Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast. Pharm Res. 2011;28(8):1895-904. doi: 10.1007/s11095-011-0417-6, PMID 21499839.

Guo Y, Laube B, Dalby R. The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model. Pharm Res. 2005;22(11):1871-8. doi: 10.1007/s11095-005-7391-9, PMID 16091994.

Scherließ R, Trows S. Novel formulation concept for particulate uptake of vaccines via the nasal associated lymphoid tissue. Procedia in Vaccinology. 2011;4:113-9. doi: 10.1016/j.provac.2011.07.016.

Shabir GA. Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Understanding the differences and similarities between validation requirements of the US Food and Drug Administration, the US Pharmacopeia and the International Conference on Harmonization. J Chromatogr A. 2003;987(1-2):57-66. doi: 10.1016/s0021-9673(02)01536-4, PMID 12613797.

Kementrian Kesehatan Republik Indonesia. Farmakope Indonesia Edisi VI. Jakarta; 2020.

ICH guidelines. Q1A (R2) stability testing of new drug substances and products. 2nd revision, International Conference on Harmonization [internet]; 2003. Available from: http://www.fda.gov/download/regulatoryinformation/Guidances/ucm128204.pdf.

Published

11-12-2021

How to Cite

MUNTU, C. M., SURINI, S., AVANTI, C., & HAYUN. (2021). PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTES OF TREHALOSE AND INULIN AS STABILIZER. International Journal of Applied Pharmaceutics, 13(4), 83–88. https://doi.org/10.22159/ijap.2021.v13s4.43823

Issue

Section

Original Article(s)

Most read articles by the same author(s)

<< < 1 2 3