Pregelatinized Starch: Variability in Gelatinization and its Influence on Product Performance
Article Sidebar
-
Functional Characteristics, Starch Retrogradation, Crystallinity, Particle Size, Birefringence, Gelatinization, Disintegrant-Binder properties, Viscosity, Disintegration test
Abstract
Starch and its derivatives are one of the significant excipients used in the pharmaceutical formulations due to their multi-purpose functionalities. The purpose of this study is two-fold: (1) Firstly, to propose a systematic approach in understanding the material properties of a starch derivative (pregelatinised starch/PGS) using analytical ‘toolbox’ as part of ‘alternative supplier sourcing’, and secondly (2) To demonstrate the effect of PGS from different vendors on the tablet disintegration using model formulations. Contextually, a two-tier characterisation procedure is generally considered as a prerequisite for establishing the sameness of the material obtained either from different batches or from various vendors. Primarily, the sameness between typical quality-control tests and compendial requirements are to be established. If similar, then sameness between the functional characteristics is to be established. In this context, the PGS from two vendors met the specifications, and there were no differences for the test results in the certificates of analysis. However, when subjected to functionality assessment, the two lots were found to be distinctly different. The influence of the functional property variations was further exemplified from viscosity results of raw material. Furthermore, this difference was even more evident when the model formulations were subjected to disintegration testing. The similarity in compendial tests but significant differences in functionality characteristics for the PGS of two vendors can be unravelled by considering variations in particle size, crystallinity, starch retrogradation and these changes are potentially attributed to the differences in the gelatinisation procedures adopted by the vendors.
Full text article
References
Abrantes, C. G., Duarte, D., Reis, C. P. 2016. An Overview of Pharmaceutical Excipients: Safe or Not Safe? Journal of Pharmaceutical Sciences, 105(7):2019–2026.
Adedokun, M. O., Itiola, O. A. 2010. Material properties and compaction characteristics of natural and pregelatinized forms of four starches. Carbohydrate Polymers, 79(4):818–824.
Alvarez-Lorenzo, C., Castro, E., Gómez-Amoza, J. L., Martínez-Pacheco, R., Souto, C., Concheiro, A. 1998. Intersupplier and interlot variability in hydroxypropyl celluloses: implications for theophylline release from matrix tablets. Pharmaceutica Acta Helvetiae, 73(2):113–120.
Bejarano, A., Nadungodage, C. H., Wang, F., Catlin, A. C., Hoag, S. W. 2019. Decision Support for Excipient Risk Assessment in Pharmaceutical Manufacturing. AAPS PharmSciTech, 20(6):223.
Charoo, N. A. 2020. Critical Excipient Attributes Relevant to Solid Dosage Formulation Manufacturing. Journal of Pharmaceutical Innovation, 15(1):163– 181.
Davani, B. 2017. Common Methods in Pharmaceutical Analysis. Pharmaceutical Analysis for Small Molecules, page 37.
Elder, D. P., Kuentz, M., Holm, R. 2016. Pharmaceutical excipients — quality, regulatory and biopharmaceutical considerations. European Journal of Pharmaceutical Sciences, 87:88–99.
Flores-Morales, A., Jiménez-Estrada, M., Mora Escobedo, R. 2012. Determination of the structural changes by FT-IR, Raman, and CP/MAS 13C NMR spectroscopy on retrograded starch of maize tortillas. Carbohydrate Polymers, 87(1):61–68.
Gamble, J. F., Chiu, W. S., Gray, V., Toale, H., Tobyn, M., Wu, Y. 2010. An investigation into the degree of variability in the solid-state properties of common pharmaceutical excipients-anhydrous lactose. Aaps Pharmscitech, 11(4):1552–1557.
Haware, R. V., Bauer-Brandl, A., Tho, I. 2010. Comparative evaluation of the powder and compression properties of various grades and brands of microcrystalline cellulose by multivariate methods. Pharmaceutical Development and Technology, 15(4):394–404.
Jaberidoost, M., Nikfar, S., Abdollahiasl, A., Dinarvand, R. 2013. Pharmaceutical supply chain risks: a systematic review. DARU Journal of Pharmaceutical Sciences, 21(1):69–69.
Kader, M. 2016. Mitigating the Risks of Generic Drug Product Development: An Application of Quality by Design (QbD) and Question based Review (QbR) Approaches. Journal of Excipients and Food Chemicals, 7(2):915–915.
Kubbinga, M., Moghani, L., Langguth, P. 2014. Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: Lactose in solid oral dosage forms. European Journal of Pharmaceutical Sciences, 61:27–31.
Kushner, I. 2013. Utilizing quantitative certificate of analysis data to assess the amount of excipient lot-to-lot variability sampled during drug product development. Pharmaceutical Development and Technology, 18(2):333–342.
Landín, M., Rowe, R. C., York, P. 1994. Particle size effects on the dehydration of dicalcium phosphate dihydrate powders. International Journal of Pharmaceutics, 104(3):271–275.
Liu, Y., Chen, J., Luo, S., Li, C., Ye, J., Liu, C., Gilbert, R. G. 2017. Physicochemical and structural properties of pregelatinized starch prepared by improved extrusion cooking technology. Carbohydrate Polymers, 175:265–272.
Moreton, C. 2019. Excipients to the year 2025-and beyond. Journal of Excipients and Food Chemicals, 10(2):29–40.
Mutungi, C., Passauer, L., Onyango, C., Jaros, D., Rohm, H. 2012. Debranched cassava starch crystallinity determination by Raman spectroscopy: Correlation of features in Raman spectra with X-ray diffraction and 13C CP/MAS NMR spectroscopy. Carbohydrate Polymers, 87:598–606.
Nickerson, B., Kong, A., Gerst, P., Kao, S. 2018. Correlation of dissolution and disintegration results for an immediate-release tablet. Journal of Pharmaceutical and Biomedical Analysis, 150:333–340.
O’laughlin, R., Sachs, C., Brittain, H., Cohen, E. 1989. Effects of variations in physicochemical properties of glyceryl monostearate on the stability of an oil- in. J Soc Cosmet Chem, 40:215–244.
Pérez-Marcos, B., Martínez-Pacheco, R., Gómez- Amoza, J. L., Souto, C., Concheiro, A., Rowe, R. C. 1993. Interlot variability of carbomer 934. Inter- national Journal of Pharmaceutics, 100(1-3):207– 212.
Ramesh, K. V., Yadav, H., Sarheed, O. 2019. Safety of Pharmaceutical Excipients and Regulatory Issues. Applied Clinical Research, Clinical Trials and Regulatory Affairs, 6(2):86–98.
Ruban, O., Pidpruzhnykov, Y., Kolisnyk, T. 2018. Excipient risk assessment: possible approaches to assessing the risk associated with excipient function. Journal of Pharmaceutical Investigation, 48(4):421–429.
Saravanan, D., Muthudoss, P., Khullar, P., Rosevenis, A. 2019. Vendor qualification: Utilization of solid state characterization “Toolbox” to assess material variability for active pharmaceutical ingredient. J Appl Pharm Sci, 9(9):1–9.
Shah, U., Augsburger, L. 2001. Evaluation of the Functional Equivalence of Crospovidone NF from Different Sources. I. Physical Characterization. Pharmaceutical Development and Technology, 6(1):39–51.
Shah, U., Augsburger, L. 2002. Multiple Sources of Sodium Starch Glycolate, NF: Evaluation of Functional Equivalence and Development of Standard Performance Tests. Pharmaceutical Development and Technology, 7(3):345–359.
Simões, M. F., Silva, G., Pinto, A. C., Fonseca, M., Silva, N. E., Pinto, R. M., Simões, S. 2020. Artificial neural networks applied to quality-by-design: From formulation development to clinical outcome. European Journal of Pharmaceutics and Biopharmaceutics, 152:282–295.
Srinivasan, A., Iser, R. 2009. FDA office of generic drugs question-based review initiative: an update-past, present, and next steps. Journal of Validation Technology, 15(2):10–10.
Thacker, A., Fu, S., Boni, R. L., Block, L. H. 2010. Inter- and Intra-Manufacturer Variability in Pharmaceutical Grades and Lots of Xanthan Gum. AAPS PharmSciTech, 11(4):1619–1626.
Ticehurst, M. D., York, P., Rowe, R. C., Dwivedi, S. K. 1996. Characterisation of the surface properties of α-lactose monohydrate with inverse gas chromatography, used to detect batch variation. Inter- national Journal of Pharmaceutics, 141(1-2):93– 99.
Whistler, R. L., Bemiller, J. N., Paschall, E. F. 2012. Starch: chemistry and technology. Academic Press.
Wöhl-Bruhn, S., Bertz, A., Kuntsche, J., Menzel, H., Bunjes, H. 2013. Variations in polyethylene glycol brands and their influence on the preparation process of hydrogel microspheres. European Journal of Pharmaceutics and Biopharmaceutics, 85(3):1215–1218.
Yu, L. X., Amidon, G., Khan, M. A., Hoag, S. W., Polli, J., Raju, G. K., Woodcock, J. 2014. Understanding Pharmaceutical Quality by Design. The AAPS Jour- nal, 16(4):771–783.
Zámostný, P., Petrů, J., Majerová, D. 2012. Effect of Maize Starch Excipient Properties on Drug Release Rate. Procedia Engineering, 42:482–488.
Zarmpi, P., Flanagan, T., Meehan, E., Mann, J., Fotaki, N. 2020. Impact of Magnesium Stearate Presence and Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties. The AAPS Journal, 22(4):75.
Zhao, N., Augsburger, L. L. 2006. The Influence of Product Brand-to-Brand Variability on Superdisintegrant Performance A Case Study with Croscarmellose Sodium. Pharmaceutical Development and Technology, 11(2):179–185.
Authors
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.