CAUSE-EFFECT RELATIONS AND OPTIMIZATION OF TABLET CONTAINING EUCOMMIA ULMOIDES AND GARDENIA JASMINOIDES SPRAY-DRIED EXTRACTS
Objective: The E. ulmoides and G. jasminoides (EG) tablets containing 67 mg E. ulmoides spray-dried extract (ESE) and 173 mg G. jasminoides spray-dried extract (GSE) were prepared by employing the direct compression method. Due to the poor flowability and compressibility of the two spray-dried extracts, various excipients were added at different ratios so that the blends can be compressed into tablets with the required standards. This study aimed at the cause-effect relations and optimization of the EG tablet formulation.
Methods: Different diluents including dibasic calcium phosphate anhydrous (DCPA), silicified microcrystalline cellulose (SMCC), spray-dried lactose (SDL) and the active ingredients (blend of ESE and GSE at the ratio of 67:173, w/w) were separately investigated their own physical properties. The binary mixtures of the active ingredients with different ratios of DCPA, SMCC, and SDL were evaluated their flowability. D-optimal design based on three independent variables (% DCPA, % croscarmellose sodium (CCS) and % SMCC) was applied to evaluate the cause-effect relations and optimize the EG tablet formulation. The weight variation, disintegration time, hardness and friability were investigated as four dependent variables.
Results: The flowability of the powders was found to be affected by the particle size distribution, particle shape and density. The three diluents could significantly improve the flowability of the active ingredients. All independent variables had significant effects on the dependent variables. An increase in % SMCC reduced the weight variation, hardness and increased the friability of tablets. Disintegration time was found to be in the negative relations with % CCS. The tablet hardness was in positive relations with % DCPA. The optimized EG tablet formulation composed of 9 % DCPA (w/w), 35 % SMCC (w/w), and 14 % CCS (w/w) of the excipient blend. The weight variation, disintegration time, hardness and friability of the optimized EG tablets were found to be 1.8 %, 11.7 min, 61.4 N, and 0.5 %, respectively.
Conclusion: The ESE and GSE could be formulated into tablet by using direct compression method. The cause-effect relations and optimization of EG tablet formulation were studied and reported for the first time.
2. Erum S, Hassan F, Hasan SMF, Jabeen S. Formulation of aspirin tablets using fewer excipients by direct compression. Pak J Pharmcol 2011;28:31-7.
3. Tong HH, Wong SY, Law MW, Chu KW, Chow AH. Anti-hygroscopic effect of dextrans in herbal formulations. Int J Pharm 2008;363:99-105.
4. Utami D, Nugrahani I, Ibrahim S. Mefenamic acid-nicotinamide co-crystal synthesized by using melt crystallization method and its solubility study. Asian J Pharm Clin Res 2017;10:135-9.
5. Chaiyasut C, Sivamaruthi BS, Makhamrueang N, Kesika P, Sirilun S, Peerajan S. Preparation and stability assessment of Perilla frutescens seed oil powder. Asian J Pharm Clin Res 2017;10:366-9.
6. The United States Pharmacopeial Convention, Rockville, MD: USP 38: The United States Pharmacopeia Convention; 2015.
7. Tomas J, Kleinschmidt S. Improvement of flowability of fine cohesive powders by flow additive. Chem Eng Technol 2009; 32:1470-83.
8. Zhang Y, Law Y, Chakrabarti S. Physical properties and compact analysis of commonly used direct compression binders. AAPS PharmSciTech 2003;4:489-99.
9. Rojas J, Kumar V. Comparative evaluation of silicified microcrystalline cellulose II as a direct compression vehicle. Int J Pharm 2011;416:120-8.
10. Rojas J, Kumar V. Effect of silicification on the tableting performance of cellulose II: a novel multifunctional excipient. Chem Pharm Bull 2012;60:603-11.
11. Shakar AAM, Razzak MSMI, Hossain MM, Arif MH, Reza MS. Effect of superdisintegrants on some physical attributes and release profile of paracetamol immediate release tablets. Bangladesh Pharm J 2012;15:89-94.
12. Kachrimanis K, Nikolakakis I, Malamataris S. Tensile strength and disintegration of tableted silicified microcrystalline cellulose: influences of interparticle bonding. J Pharm Sci 2003;92:1489-501.
13. Mohanachandran PS, Sindhumol PG, Kiran TS. Superdisintegrants: an overview. Int J Pharm Sci Rev Res 2011;6:105-9.
14. Ferrero C, Munoz N, Velasco MV, Munoz-Ruiz AR, Jimenez-Castellanos R. Disintegrating efficiency of croscarmellose sodium in a direct compression formulation. Int J Pharm 1997;147:11-21.
15. Van Veen B, Bolhuis GK, Wu YS, Zuurman K, Frijlink HW. Compaction mechanism and tablet strength of unlubricated and lubricated (silicified) microcrystalline cellulose. Eur J Pharm Biopharm 2005;59:133-8.
16. Solaiman A, Suliman AS, Shinde S, Naz S, Elkordy AA. Application of general multilevel factorial design with formulation of fast disintegrating tablets containing croscaremellose sodium and disintequick MCC-25. Int J Pharm 2016;501:87-95.