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

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Pilani Campus
MULTI UNIT
PARTICULATE SYSTEM -
TABLET

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 Introduction- MULTI UNIT PARTICULATE
SYSTEM
 MUPS TABLETS
 Advantages
 Biopharmaceutics
 Formulation variables
 Characterization
 Examples of MUPS tablets
 Practical approach
TODAY
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• 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
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1. Dose uniformity
2. Excellent flow property
3. Easy of dosing without changing the process and
formulation
4. Can deliver incompatible bioactive agents
5. Can be dispersed in lumen and easily available for
absorption
6. Inter and intra patient variability is lesser
7. Low risk of dose dumping
8. Very less affected by presence of food in lumen
Advantage
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Flexibility of MUPS

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PELLETIZATION TECHNIQUES
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1. Powder Layering

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2. Solution/suspension layering
PELLETIZATION TECHNIQUES
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3. Extrusion spheronization
4. Melt Extrusion
PELLETIZATION TECHNIQUES
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Types of pellets
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Compression of MUPS
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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
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 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
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Variables
Formulation
variables
Process
variables
Equipment
variables
Factors influencing MUPS
tablets
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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
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Solubility
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Solubility
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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
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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
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Compaction of the pellets –
Increase in the compaction pressure- rupture in the coating
layer
Lubricant amount decreased to .25%- increase in hardness
Cushioning excipients
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MECHANISMS OF RELEASE FROM COATED
PELLETS
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1. Solution/Diffusion
2. Dissolving coating layer

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1. Pellets size distribution
2. Pellets shape
3. Surface morphology (SEM)
4. Specific surface area
5. Friability
6. Disintegration Time
7. Dissolution
8. Density
9. Porosity
Characterization
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MARKETED FORMULATIONS

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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)
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References
1. Isaac Ghebre-Sellassie, Multiparticulate oral drug delivery, informa healthcare
New York: Marcel Dekker (1994).
2. R. Bodmeier(1997), European journal of pharmaceutics and biopharmaceutics,
vol. 43, pp. 1-8.
3. T.E. Beckert et al., Compression of enteric-coated pellets to disintegrating tablets
International Journal of Pharmaceutics 143 (1996) 13-23.
4. T.E. Beckert et al., Compression of enteric-coated pellets to disintegrating
tablets:uniformity of dosage units, Powder Technology 96 (1998) 248-254
5. 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