Manufacture of granulates containing high potency drugs

Česká verzia

Authors: A. Franc; M. Rabišková
Authors place of work: Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta, Ústav technologie léků
Published in the journal: Čes. slov. Farm., 2010; 59, 51-58
Category: Přehledy a odborná sdělení

Summary

Granulation is one of the most widely spread technological procedures in the manufacture of solid oral dosage forms. With regard to the safety of work in the manufacture of tablets containing highly potent active ingredients, devices with a closed construction which during the process of manufacture prevent contamination of the surroundings and decrease health risk for the personnel are more widely used. They include one-step high-speed granulators, fluid granulators and integrated granulating systems connecting high-speed granulation with fluid drying. These devices make it possible to automate the whole process and they are equipped with automatic cleaning. The individual technologies possess certain advantages as well as disadvantages. When considering installation of these devices, it is necessary to evaluate not only the processual parameters such as robustness, length of process, easy maintenance, easy cleaning, and technological background, and also take into consideration the decisive qualitative requirements for the drug in detail. In granulates, they include primarily such parameters as density, flow properties and distribution of particle size, and in tablets, besides routine quality indices, also mechanical endurance and dissolution.

Key words:
one-step granulation – granulation units – high potency drugs – safety

Zdroje

1. Rowe, R. C.: Polar/nonpolar interactions in the granulation of organic substrates with polymer binding agents. Int. J. Pharm., 1989; 56, 117–124.

2. Frömming, H. K., Szejtli, J.: Pharmaceutical technological aspects of cyclodextrins in drug formulation. In: Frömming, H. K., Szejtli, J.: Cyclodextrins in pharmacy, 1. ed. Dordrecht: Springer 1994; 126–148.

3. Žádost o povolení/změnu v povolení k výrobě léčivých přípravků, změny k povolení výrobě léčivých přípravků a pokyny pro poskytování bližších údajů ve výrobû. Pokyn SÚKL VYR-27 verze 2. srpen 2006. http://www.sukl.cz/vyr-27-verze-2 (22. 2. 2010).

4. Duschler, G., Carius, W., Bauer, K. H.: Single-step granulation: development of a vacuum based IR drying method (Pilot Scale Results) Drug. Dev. Ind. Pharm., 1997; 23, 119–126.

5. Giry, K., Viana, M., Genty, M., Louvet, F., Wüthrich, P., Chulla, D.: Comparison of single pot and multiphase granulation. Part 2: Effect of the drying process on granules manufactured in a single pot granulator and dried either in situ or in a fluid bed dryer. Pharm. Dev. Tech., 2009; 14, 149–158.

6. Stahl, H.: Single-pot systems for drying pharmaceutical granules. Pharm. Tech. Eur., 2000; 12, 23–34.

7. Stahl, H.: Tabletten aus dem eintopf. Chem. Tech., 1996; 8, 32–33.

8. Waldron, M. S.: Microwave vakuum drying of pharmaceuticals: the development of a process. Pharm. Eng., 1988; 8, 9–13.

9. Ameye, D., Keleb, E., Vervaet, Ch., Remon, J. P., Adams, E., Desire L. M.: Eur. J. Pharm. Sci., 2002; 17, 247–251.

10. Bauer, K., Vadagdini M.: New developments in wet granulation. Pharm. Tech. Eur., 1997; 9, 27–34.

11. Parikh, D. M.: Handbook of pharmaceutical granulation technology, 1 ed. New York: Marcel Dekker Inc., 1997; 304–330.

12. Design for Cleanability and Maintenance, GEA Pharma systems India, http://www.gea-pharma.in/GPSIN/cms doc.nsf/WebDoc/ndkw73gh2q (20. 11. 2009).

13. Hegedıs, A., Pintye-Hódi, K.: Comparison of the effects of different drying techniques on properties of granules and tablets made on a production scale. Int. J. Pharm., 2007; 330, 99–104.

14. Lindermann D., Ducker, D., Tegtmeier, M.: Use of the single pot technology in the production of drugs from plants. Pharm. Ind., 1998; 60, 801–803.

15. Fexer, W., Gruber, E.: Fluidized bed granulates that have a high proportion of fruit. Patentová dokumentace: US2008199592 (A1). (21. 8. 2008).

16. Fluid bed drying. GEA Process Engineering Ltd. http://www.niro.co.uk/nuk/cmsdoc.nsf/WebDoc/ndkw73ej jw (20. 11. 2009)

17. Simon, E. I.: Industrial installations for trapping and regeneration of organic solvents during drying in a fluidized bed (a review). Pharm. Chem. J., 1978; 12, 1507–1513.

18. Mehrotra, A. Muzzio, J.: Comparing mixing performance of uniaxial and biaxial bin blenders. Powder Technol., 2009; 196, 1–7.

19. Agglomeration, granulation and rating. GEA Niro. http://www.niro.com/niro/cmsdoc.nsf/WebDoc/ndkw74ml 2z (20.11.2009)

20. Gao, Z. H., Jain, A. Motherama, R., Graya, D. B., Hussaina, M. A.: Fluid bed granulation of a poorly water soluble, low density, micronized drug: comparison with high shear granulation. Int. J. Pharm., 2002; 237, 1–14.

21. Chaplin, G., Pugsley, T., Winters, C.: Monitoring the fluidized bed granulation process based on S-statistic analysis of a pressure time series, AAPS Pharm SciTech., 2005; 6(2), E198-E201. http://www.aapspharmscitech.org/

22. Sharareh, S. B., Klocker, B. J., Hüttlin, H., Wolschann P., Viernstein, H.: Validation of fluid bed granulation utilizing artificial neural network. Int. J. Pharm., 2005; 291, 139–148.

23. Kovaleski, J., Kraut, B., Mattiuz, A., Giangiulio, M., Brobst, G., Cagno, W., Kulkarni, P., Rauch, T.: Impurities in generic pharmaceutical development. Adv. Drug Deliv. Rev., 2007; 59, 56–63.

24. High shear bottom-drive mixing and granulation by Aeromatic-Fielder™. GEA Pharma Systems. http://www.

gea-ps.com/npsportal/cmsdoc.nsf/WebDoc/ ndkw73taq (20. 11. 2009)

25. Schenck, L. R., Planka, R. V.: Impact milling of pharmaceutical agglomerates in the wet and dry states. Int. J. Pharm., 2008; 348, 18–26.

26. Design for cleanability and maintenance. GEA Pharma System. http://www.gea-ps.com/npsportal/cmsdoc.nsf/WebDoc/ndkw73haj7 (20. 11. 2009).

27. Immediate release solid oral dosage forms – scale-up and post approval changes: Chemistry guidance for industry, chemistry, manufacturing, and controls, in vitro dissolution testing, and in vivo bioequivalence documentation. CDER. 1999. http://www.fda.gov (20. 11. 2009).

28. SUPAC-IR/MR: Immediate release and modified release solid oral dosage forms, Guidance for industry, Manufacturing equipment addendum. Rev. ed. CDER. 1999. http://www.fda.gov (20. 11. 2009).

29. Rantanen, J., Jørgensen, A., Räsänen, E., Luukkonen, P., Airaksinen, S., Raiman, J., Hänninen, K., Antikainen, O., Yliruusi, J.: Process analysis of fluidized bed granulation, AAPS PharmSciTech. 2001; 2(4): article 21. http://www.aapspharmscitech.org.

30. Hausman, D. S.: Comparison of low shear, high shear and fluid bed granulation during low dose tablet process development. Drug Dev. Ind. Pharm., 2004; 30, 259–266.

31. Kristensen, J, H.: Wet Granulation in Rotary Processor and Fluid Bed: Comparison of Granule and Tablet Properties. AAPS PharmSciTech. 2006; 7(1): Article 22. http://www.aapspharmscitech.org. (20. 11. 2009).

32. Giry, K., Viana, M., Genty, M., Louvet, F., Wüthrich, P., Chulia, D.: Comparison of single pot and multiphase granulation. Part 1: Effect of the high shear granulation on granule properties according to the drug substance and its concentration. Pharm. Dev. Tech., 2009; 14, 138–148.

33. Giry, K., Viana, M., Genty, M., Wüthrich, P., Chulia, D.: Multiphase versus single pot granulation process: influence of process and granulation parameters on granules properties. Drug. Dev. Ind. Pharm., 2006; 32, 509–530.

34. Chalabala, M., Rabišková, M.: Kvalifikované osoby ve výrobě, distribuci a kontrole medikovaných premixů a ve výrobě a uvádění medikovaných krmiv. In: Sborník, modul III. VFU Brno, 2002–2003; 220.

35. Komárek, P., Rabišková, M.: Technologie léků, 3. vyd. Praha: Galén 2006; 228–241.

36. Lunney, D. P., Anderson, C. A: Investigation of the statistical power of the content uniformity tests using simulation studies. J. Pharm. Innovation., 2009; 4, 24–35.

37. Rabišková, M., Masteiková, R., Chalupová, Z., Dvořáčková, K.: Lékové formy a biofarmacie II: Tuhé léky. Brno: Veterinární a farmaceutická univerzita 2009; 67.

38. Stahl, H.: Comparing different granulation techniques. Pharm. Tech. Eur., 2004; 11, 23–33.

39. Gavrilov, A. S., Gusel’nikova, Petrov, E. V., Yu, A.: Development of the technology of activated charcoaltablets, Pharm. Chem. J., 2004; 38, 41–44.

40. BrOEckel, U., Beilharz, H.: Effect of the microstructure of paracetamol granules on tablet properties. European Congress of Chemical Engineering. Copenhagen. September 2007. http://www.nt.ntnu.no/users/skoge/prost/proceedings/ecce6_sep07/upload/extra-abstractsvolume1/1761-s8-c.pdf (20. 11. 2009).

41. Gordon, S. M.: Process consideration in reducing tablet friability and their effect on in vitro dissolution. Drug.

Dev. Ind. Pharm., 1994; 20, 11–29.