USING RANDOM BALANCE METHOD TO DEVELOP QUANTITATIVE COMPOSITION OF DAPAGLIFLOZIN TABLETS
DOI:
https://doi.org/10.11603/2312-0967.2025.1.15275Keywords:
dapagliflozin, tablets, random balance method, direct compression, amount of excipient, scatter plot, quality attributeAbstract
The aim of the work was to study the influence of excipients amount on the quality attributes of the tablet blend and tablets dapagliflozin using the random balance method.
Materials and Methods. The study used Dapagliflozin propanediol monohydrate, MCC 102, anhydrous lactose, crospovidone XL-10, colloidal anhydrous silicon dioxide (aerosil 200), magnesium stearate. The formulations were designed according to the random balance method. During the experiment, the appropriate amount of excipients was added to the Dapagliflozin propanediol monohydrate according to the planning matrix. Tablets were manufactured by direct compression. To characterise the quality of the resulting dosage form, there were analysed in accordance with the general pharmacopoeial articles for powders and tablets. The study was conducted on modern equipment.
Results and Discussion. The bulk density and tablet blend slope were improved with increase in the amount of lactose anhydrous 22 AN. Results of tablet blend slope and disintegration depended on amount of crospovidone XL-10. The decrease in the amount of aerosil 200 the bulk density and tapped density increase, ipmrove flowability and tablet blend slope. Higher hardness of tablets dapagliflozin was obtained by using lower amount of magnesium stearate.
Conclusions. Using the random balance method, the amount of 4 excipients at 3 levels was studied. According to the results of the study, it was found that the advantages of quality attributes were obtained when using 30.365 mg of lactose anhydrous 22 AN, 5 mg of crospovidone XL-10, 1.25 mg of colloidal silicon dioxide anhydrous (aerosil 200) and 0.625 mg of magnesium stearate per tablet. As a result of the experimental studies, the optimal composition of Dapagliflozin, 5 mg tablet cores were proposed.
References
ICH Q8(R2) pharmaceutical development. Part I: pharmaceutical development, and. Part II: annex to pharmaceutical development. 2009. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_ Guideline.pdf
Koeberle M, Schiemenz W. QbD: Improving Pharmaceutical Development and Manufacturing Workflows to Deliver Better Patient Outcomes. Pharmaceutical Technology, Outsourcing Resources. 2017; 2017 Suppl(4):s20-s23.
ICH Q9: quality risk management. ICH harmonised tripartite guidelines. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 2005. https://ich.org/news/ ich-q9r1-guideline-reaches-step-4-ich-process.
ICH Q10 pharmaceutical quality system. 2008. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf.
Shi C, Zhao H, Fang Y, Shen L, Zhao L. Lactose in tablets: Functionality, critical material attributes, applications, modifications and co-processed excipients. Drug Discovery Today. 2023;28(9):103696. DOI: 10.1016/j.drudis.2023.103696. DOI: https://doi.org/10.1016/j.drudis.2023.103696
Zhou S-F, Zhong W-Z. Drug Design and Discovery: Principles and Applications. Molecules 2017;22(2):279. DOI: 10.3390/molecules22020279. DOI: https://doi.org/10.3390/molecules22020279
Hroshovyi TA, Martseniuk VP, Kucherenko LI, Vronska LP, Hureieva SM. Mathematical planning of an experiment during scientific research in pharmacy [Matematychne planuvannia eksperymenta pry provedenni naukovykh doslidzhen v farmatsii]. Ternopil, Ukrmedknyga; 2008. 368 p.
Panysheva O. Development of Formulation and Technology of Combined Generic Powder for Oral Solution in Sachets Based on the Quality by Design Approach. Global Journal of Medical Research: B Pharma, Drug Discovery, Toxicology & Medicine. 2022;22(B2):78-92. DOI: https://medicalresearchjournal.org/ index.php/GJMR/article/view/102201.
Zablotskaya K, Ahmed M, Zablotskiy S, Minker W. Non-parametric Regression and Random Balance Method Modification for Determination of the Most Informative Features. Sixth International Conference on Intelligent Environments: 2010;64-67. DOI: 10.1109/IE.2010.19. DOI: https://doi.org/10.1109/IE.2010.19
Chernetska S, Beley N, Demchuk M () The method of random balance for studying the influence of excipients quantities on the technological parameters of tablets based on Origanum vulgare L. dry extract. EUREKA: Health Sciences. 2021;2:73-81. DOI: 10.21303/2504-5679.2021.001664. DOI: https://doi.org/10.21303/2504-5679.2021.001664
Behei N, Tryhubchak O, Pryymak B. Development of amlodipine and enalapril combined tablets based on quality by design and artificial neural network for confirming of qualitative composition. Pharmacia. 2022;69(3):779-89. DOI: 10.3897/pharmacia.69.e86876. DOI: https://doi.org/10.3897/pharmacia.69.e86876
Pharmaceutical composition comprising dapagliflozin. Patent WO2021165316A1.2021.
Zhao H, Shi C, Zhao L, Wang Y, Shen L. Influences of different microcrystalline cellulose (MCC) grades on tablet quality and compression behaviour of MCC-lactose binary mixtures. Journal of Drug Delivery Science and Technology. 2022;77:103893. DOI: 10.1016/j.jddst.2022.103893. DOI: https://doi.org/10.1016/j.jddst.2022.103893
JRS Pharma: VIVAPUR® Microcrystalline Cellulose. https://www.jrspharma.com/pharma_en/products/excipients/vivapur.php.
Ujjwal S, Sheeba FR, Santosh K. Formulation and evaluation of fast dissolving tablets containing a combination of valsartan and amlodipine for the treatment of hypertension. World Journal of Pharmaceutical Sciences 2016;4(11):147-52.
Ramírez DG, Robles LV. Contrasting the crospovidones functionality as excipients for direct compression. Brazilian Journal of Pharmaceutical Sciences. 2015;51(1):155-71. DOI: 10.1590/S1984-82502015000100016 DOI: https://doi.org/10.1590/S1984-82502015000100016
Wang J. Moisture adsorption and desorption properties of colloidal silicon dioxide and its impact on layer adhesion of a bilayer tablet formulation. Journal of Excipients and Food Chemicals. 2014;5(1):21-31.
ZAO FPK Pharm VILAR. Aeroperl® 300 Pharma by Evonik Industries AG - the optimal solution for increasing the solubility of active pharmaceutical ingredients. Pharmaceutical Industry review. 2017;6(65):86-9.
Uzunović A, Vranić E. Effect of magnesium stearate concentration on dissolution properties of ranitidine hydrochloride coated tablets. Bosn J Basic Med Sci. 2007;7(3):279-83. DOI: 10.17305/bjbms.2007.3060. DOI: https://doi.org/10.17305/bjbms.2007.3060
European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia. 10th ed. Strasbourg: Council of Europe; 2021. 1084 p.
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