PREPARATION AND SCALE-UP STUDY OF TREATED FAMOTIDINE FOR THE DEVELOPMENT OF ORALLY DISINTEGRATING TABLETS USING A COMPLEX FLUIDIZED-BED GRANULATOR EQUIPPED WITH A PARTICLE-SIZING MECHANISM
Objective: Bitter taste-masked drug substance should be needed for the development of orally disintegrating tablets (ODT). We selected a new type of a complex fluidized-bed granulator equipped with a particle-sizing mechanism for treating famotidine (FAM). This study was conducted to demonstrate the critical process parameter, which controls particle size of treated FAM, to determine its acceptable particle size considering uniformity of assay and to perform scale-up study from a laboratory scale to a commercial scale.
Methods: Particle size of treated FAM was evaluated by changing spraying air pressure on the operation of a complex fluidized-bed granulator. Uniformity of assay in granules after blending and tablets were compared at different particle size of treated FAM. On the scale-up study, particle size and assay of treated FAM in both scales were evaluated.
Results: The particle size of treated FAM decreased as the increase in spraying air pressure in relation to the spraying mist size. Better uniformity of assay was observed when the diameter of treated FAM was 20 Âµm compared to that of 50 Âµm. Therefore, target particle size of treated FAM was set at approximately 20 Âµm. Similar qualities could be obtained between both scales in the points of particle size and assay.
Conclusion: On the operation of a complex fluidized-bed granulator, spraying air pressure was the critical process parameter that controlled particle size of treated FAM. On Scale-up study of treated FAM, spraying air pressure in relation to the spraying mist size was important.
2. Sakamoto H. State of art technology of granulation and coating by newly developed Wurster processor. Design of taste masking and rapidly disintegrating tablet using super fine particles coater (SPC). Pharm Tech Japan 2005;21:1149â€“59.
3. Terashita K, Natsuyama S, Nagato T, Kanou Y, Namba N. Development of new design complex fluidized bed device with particle sizing mechanism for fine particle coating and fine granulation. Pharm Tech Japan 2004;20:105â€“13.
4. Hosaka S, Okamura Y, Tokunaga Y. Preparation of fine particles with improved solubility using a complex fluidized-bed granulator equipped with a particle-sizing mechanism. Chem Pharm Bull 2016;64:644-9.
5. Kimura S, Iwao Y, Ishida M, Uchimoto T, Miyagishima A, Sonobe T, et al. Optimal conditions to prepare fine globular granules with a multi-functional rotor processor. Int J Pharm 2010;391:244â€“7.
6. Kimura S, Iwao Y, Ishida M, Noguchi S, Itai S, Uchida S, et al. Evaluation of the physicochemical properties of fine globular granules prepared by a multi-functional rotor processor. Chem Pharm Bull 2014;62:309â€“15.
7. CC Cole. Pharmaceutical Coating Technology: Tayler and Francis; 1995. p. 1.
8. Funtaikiki Souchi Handbook: The Nikkan Kogyo Shimbun, Ltd.; 1995. p. 413.
9. Fukumori Y, Ichikawa H, Yamaoka Y, Akaho E, Takeuchi Y, Fukuda T, et al. Effect of additives on physical properties of fine ethyl cellulose microcapsules prepared by the wurster process. Chem Pharm Bull 1991;39:164â€“9.
10. Hasegawa A, Nakagawa H, Sugimoto I. Damage of microcapsule wall during compression. Yakugaku Zasshi 1984;104:889â€“95.
11. Shimizu T, Nakano Y, Morimoto S, Tabata T, Hamaguchi N, Igari Y. Formulation study for lansoprazole fast-disintegrating tablet. I. Effect of compression on dissolution behavior. Chem Pharm Bull 2003;51:942â€“7.
12. Yuasa H, Kanaya Y, Omata K. Studies on internal structure of tablets. III.: Manufacturing of tablets containing microcapsules. Chem Pharm Bull 1990;38:752â€“6.
13. Mizumoto T, Tamura T, Kawai H, Kajiyama A, Itai S. Formulation design of an oral, fast-disintegrating dosage form containing taste-masked particles of famotidine. Chem Pharm Bull 2008;56:946â€“50.
14. Watano S, Sato Y, Miyanami K. Scale-up of agitation fluidized bed granulation. IV. Scale-up theory based on the kinetic energy similarity. Chem Pharm Bull 1995;43:1227â€“30.
15. Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms: U. S. Food and Drug Administration (FDA); 2012.
16. Project report meeting of GMP committee of drug substance: Parenteral Drug Association-Japan Chapter; 2008.
17. Watano S, Sato Y, Miyanami K, Murakami T, Ito Y, Kamata T, et al. Scale-up of agitation fluidized bed granulation. I. Preliminary experimental approach for optimization of process variables. Chem Pharm Bull 1995;43:1212â€“6.