Mups tablets

Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as a number of small independent subunits. These sub units are compressed to form MUPS tablets

1. MULTI UNIT PARTICULATE SYSTEM - TABLET

2. Introduction- MULTI UNIT PARTICULATE SYSTEM MUPS TABLETS Advantages Biopharmaceutics Formulation variables Characterization Examples of MUPS tablets Practical approach TODAY 07/03/2015 2 Presentation for Micro labs, Mumbai

3. Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as a number of small independent subunits. Multiparticulates are discrete particles that make up a multiple unit system. Those multiparticulates can be granules, milispheres , pelletes , spheroids etc but sometimes used synomously . The agglometrates of powder to give narrow size range of 0.5 -2mm of nearly spherical, free flowing particles and low porocity particle called as pellets Introduction Presentation for Micro labs, Mumbai 07/03/2015

4. Dose uniformity Excellent flow property Easy of dosing without changing the process and formulation Can deliver incompatible bioactive agents Can be dispersed in lumen and easily available for absorption Inter and intra patient variability is lesser Low risk of dose dumping Very less affected by presence of food in lumen Advantage Presentation for Micro labs, Mumbai 07/03/2015

5. Presentation for Micro labs, Mumbai 07/03/2015 Flexibility of MUPS

6. PELLETIZATION TECHNIQUES Presentation for Micro labs, Mumbai 07/03/2015 1. Powder Layering

7. 2. Solution/suspension layering PELLETIZATION TECHNIQUES Presentation for Micro labs, Mumbai 07/03/2015

8. 3. Extrusion spheronization 4. Melt Extrusion PELLETIZATION TECHNIQUES Presentation for Micro labs, Mumbai 07/03/2015

9. Types of pellets Presentation for Micro labs, Mumbai 07/03/2015

10. Compression of MUPS Presentation for Micro labs, Mumbai 07/03/2015

11. 1 . Target drug release profiles must be attained in a reproducible manner. 2. Drug release characteristics should not be sensitive to minor changes in coating formulations or coating process conditions. 3. The coating formulations and coating processes should ideally be uncomplicated and facilitate scale-up from the laboratory into production. 4. The final product should be stable and, in particular, be devoid of significant time-dependent changes in drug release characteristics. 5. The coating formulations and coating process must be cost-effective. 6. The entire process (from initial development in the laboratory to ultimate product commercialization) must have a sound scientific basis so as to withstand the regulatory challenges that precede the introduction of any pharmaceutical product Target for sucessful formulation Presentation for Micro labs, Mumbai 07/03/2015

12. Loss of integrity of the polymer coat affecting the drug release from reservoir system Deformation Friability of the compressed tablet Segregation of the particles Issues during compression Presentation for Micro labs, Mumbai 07/03/2015

13. Factors influencing MUPS tablets Presentation for Micro labs, Mumbai 07/03/2015

14. Core pellets- type, composition ,size , elasticity Coating on pellets Preferred- water(HPMC,MC, Methocel types E3 and E5 and Pharmacoat 603 and 606 )- 5-10% solution. Organic solvents Solvent mixtures- Most of the cellulose derivatives. Platicizers Cushioning excipients- Nature, Size, Amount, porosity Formulation variables Presentation for Micro labs, Mumbai 07/03/2015

15. Solubility Presentation for Micro labs, Mumbai 07/03/2015

16. Solubility Presentation for Micro labs, Mumbai 07/03/2015

17. 1. Improve the mechanical properties of the coating by reducing brittleness, increasing flexibility and reducing the elastic modulus of the polymer. 2. Reduce the glass transition temperature, and thus the minimum film-forming temperature , of aqueous polymeric dispersions. Platicizers Presentation for Micro labs, Mumbai 07/03/2015

18. Pellets to cushioning excipients ratio, Excipients should be more than 50% is consider better because pellets above 50% increases the friability. Excipients should be able to form hard and rapidly disintegrating tablet Relation between yield pressure of excipients and pellets Generally used excipients, PEG (3350-6000)> MCC> Crospovidone > Lactose> DCP Combination of cushioning excipients - 50% MCC, 25% PEG, 25% crosspovidone Ref . Torrado JJ, Augsburger LL. Effect of different excipients on the tableting of coated particles. Int. J. Pharm. 1994 Cushioning excipients Presentation for Micro labs, Mumbai 07/03/2015

19. Compaction of the pellets – Increase in the compaction pressure- rupture in the coating layer Lubricant amount decreased to .25%- increase in hardness Cushioning excipients Presentation for Micro labs, Mumbai 07/03/2015

20. MECHANISMS OF RELEASE FROM COATED PELLETS Presentation for Micro labs, Mumbai 07/03/2015 Solution/Diffusion Dissolving coating layer

21. Pellets size distribution Pellets shape Surface morphology (SEM) Specific surface area Friability Disintegration Time Dissolution Density Porosity Characterization Presentation for Micro labs, Mumbai 07/03/2015

22. MARKETED FORMULATIONS

23. Characterization of tablet Hardness Dimensions Disintegration time Colour Shape Characterization of tablet particles Disintegrated and dried tablet- seive analysis for pellets to excipients ratio Total weight of pellets in each tablet Total coat on the pellets= Total weight of pellets in each tablet- Core pellets weight Drug coating estimation Use Design of experiment Generic MUPS tablets(Practical approach) Presentation for Micro labs, Mumbai 07/03/2015

24. References Isaac Ghebre-Sellassie , Multiparticulate oral drug delivery, informa healthcare New York : Marcel Dekker ( 1994). R. Bodmeier (1997), European journal of pharmaceutics and biopharmaceutics, vol. 43, pp. 1-8 . T.E. Beckert et al ., Compression of enteric-coated pellets to disintegrating tablets International Journal of Pharmaceutics 143 (1996) 13-23. T.E. Beckert et al., Compression of enteric-coated pellets to disintegrating tablets:uniformity of dosage units, Powder Technology 96 (1998) 248-254 A . Debunne et al ., Compaction of enteric-coated pellets: influence of formulation and process parameters on tablet properties and in vivo evaluation, European Journal of Pharmaceutical Sciences 22 (2004) 305–314