Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Multiple-Unit Pellet System (MUPS):

A Review
PRIYANKA BOTE
(Department of Quality assurance)
Pravara Rural Education Society,
College of Pharmacy for Women Chincholi, Nashik(MS)

Vinayak Gaware,
HOD of department of pharmaceuticalChemistry.

Corresponding author*: Sanjay Kumar Panda.

Abstract:- Pelletization is a technique to convert drugs minimize local irritation of the mucosa for certain irritant
or excipients to small free flowing, spherical or semi drugs.2
spherical units, which are produced by agglomerating
fine powdered drug/excipients with a binder solution. Pellets may be produced by different methods based on
Pellets range in size, typically, between 0.5 – 2.0 mm. their application and the choice of manufacturer. The most
MUPS (Multiple Unit Pellet Systems) are multi- widely used processes are extrusion and spheronization,
particulate in nature and are administered as tablets. solution or suspension layering, and powder layering. Other
These tablets disperse in stomach and intestine allowing processes with limited application in the development of
constant drug release in systemic circulation. This article pharmaceutical pelletized products include globulation,
reviews the advantages, disadvantages, common balling, and compression. The compression of pellets into
industrial technique for preparation of pellets and tablets is a novel technology and is much more ideal than
challenges in manufacturing of MUPS. filling them into capsule.3,4.

Keywords:- MUPS, Pellets, Tablets, Compaction, II. MUPS TABLETS

Compression, Tableting, Spheronization.
MUPS tablets are widely used in solid dosage form
I. INTRODUCTION design5, 6,. MUPS is advantageous in comparison to
monolithic dosage forms. Combination of drug substances
The oral route of drug administration is the most and release profiles can be provided by formulating the
important and most user-friendly route of administration. In MUPS tablets with different pellet qualities or combining
recent years, Multiple Unit Pellet Systems (MUPS) tablets pellets with drugs in powder or granulated form. MUPS
are widely used in solid dosage form design. MUPS is tablet contains several hundred of coated pellets of active
considered to provide pharmacokinetic advantages pharmaceutical ingredients which delivered the drug at
compared to monolithic dosage forms. Typically, modified predetermined rate and absorption to provide constant blood
release pellets are contained in MUPS tablets. Modified profile. MUPS are easily administered as disintegratable
release drug delivery systems have acquired very important tablet which disperse into their subunits across the stomach
role in pharmaceutical research and development.1 Pellets and the small intestine, leading to predictable oral transition
are produced primarily for the purpose of oral modified and constant bioavailability 7, 8.
release forms having gastro resistant, sustained-release
properties and the capability of Pulsatile Drug Delivery A. Objectives for the preparation of MUPS Tablets
Systems. For such purposes, coated pellets are administered Following are some of the objectives and current
in the form of hard gelatin capsules or disintegrating tablets application areas of MUPS tablets:
that quickly disperse in the stomach. The safety and efficacy  For controlled release drug delivery system.
of the formulation is higher than that of other dosage forms.  For enteric release and colon targeted drug delivery
Pellets provide high degree of flexibility during the design system.
and development of oral dosage forms. They can be divided  Designing of Mouth-melting taste-masked dosage form.
into desired dose without formulation or process changes,  Combining of drugs with different release patterns in the
and can also be blended to deliver incompatible agents same dosage form.
simultaneously or particles with different release profiles at  Increasing the drug dose administered in controlled
the same site or at different sites within the gastrointestinal release form as compared to that possible with capsules.
tract. Orally administered pellets generally disperse freely in  Enhancing stability of dosage form as compared to its
the gastrointestinal tract and maximize the drug absorption, capsule counterpart.

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Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
 Obviating the need for specialized packaging. III. METHODS OF PELLETIZATION16, 17, 18

B. Advantages of Pellets Compaction and drug layering are the most widely
Following are some of the advantages of using pellets: used pelletization techniques. Other methods such as
 Possibility of developing different dosage strengths globulation, balling are also used in development of pellets in
without process/formulationchanges9. a limitedscale. Some of the desirable properties of the pellets
 Pellets have stable therapeutic effects over single unit include pellets shape should be near spherical and have a
dosage forms10-11. smooth surface; both considered important characteristics
 Pellets can also be used to provide different release profile for subsequent film coating. Additionally, the particle size of
at the same or differentsites in the gastrointestinal tract. pellets should be as narrowas possible. The optimum size of
 Pellets offer high degree of flexibility in the design and pellets for pharmaceutical use is considered to be between
development of oral dosageform like suspension, sachet, 0.5 and 1mm.
tablet and capsule12-13.
A. Powder layering:
 Pellets disperse freely in gastro intestinal tract, increasing Powder layering involves the deposition of dry powders
drug absorption, and reducing local irritation of the of drugs and excipients on neutral spheres with the help of
mucosa by certain irritant drugs14. binding liquids. Powder layering involves simultaneous
 Pellet-released active ingredients may offer a greater addition of binding agents and dry powders; hence it requires
bioavailability than usual drugs. specialized equipmentslike spheronizer. If the process is set-
 Good tolerability - it reduces side effects by maintaining up properly, hourly weight gains up to 300% are possible,
plasma levels within the therapeutic zone. It delivers which indicates the processing option is very fast and
steady plasma levels hour by hour for day and night efficient.
control 15.
 Better patient compliance - Orally disintegrating MUPS B. Solution / suspension layering:
tablet having a palatable taste which is suitable for Solution/suspension layering involves the deposition of
pediatric and geriatric patients who cannot swallow tablet solution or suspensions of drugsubstances and binder over
or capsule, e.g. Prevacid SoluTab. the neutral spheres. Consequently conventional coating
pans, fluid bed processor, centrifugal granulators, wurster
coaters have been used successfully to manufacture pellets
by this method. To achieve uniform layers the bottom spray
method should be the processing option of choice. Average
weight gain per processing hour is about 15-20 %, because
80 – 85 % liquid vehicle have to be evaporated.

Fig. 1: Principle of Powder Layering and Solution/Suspension Layering (researchgate.net)

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Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165

Fig. 2: Principle of extrusion and spheronization process

(researchgate.net)

C. Extrusion and Spheronization: IV. TYPES OF MULTI UNIT DOSAGE

This processing option is the oldest known industrial FORMS
pelletizing technique. First all ingredients are blended, then
by adding liquid a wet dough is formed, which is passed With regards to the final dosage form, the multi
through an extruder with defined dye sizes. particulates are usually formulated into singleunit dosage
forms such as filling them into hard gelatin capsules or
Other pelletization methods such as globulation, sachets or compressing them into tablets or suspended in a
cryopelletization, spray drying, spray congealing, balling, suspending media with suitable suspending agent at an
and compression are used, although on a limited scale in the appropriate pH.
preparation of pharmaceutical pellets.

Fig. 3: Flexibility of pellets in development of dosage form(researchgate.net)

V. APPLICATION OF MUPS • Combination of drug substances and release profiles can

be provided by formulating the MUPS tablets with
• To protect drugs that are unstable in acid from different pellet qualities or combining pellets with APIs in
disintegrating in the gastric juice e.g. antibiotics enzymes, powder or granulated form. 21, 22
peptides proton pump inhibitors.19
• pH Dependent controlled release of drugs for optimal
absorption
• GI targeting of different sections of small intestine or of
the colon (absorption window, targeting localized effects).
• Colon targeting for local treatment and systemic therapies.
The key to controlling the release of the drug is the pH
dependent dissolution of the film coating, which takes
advantage of the different pH values that exist along the
gastrointestinal tract. Since the coatings dissolution is
controlled by pH, or by gradually permeability, the drug is
release in a precise manner in specific sections of the
digestive tract, or at specific times after intake.20

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Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
VI. COMPRESSION OF MUPS pellets, brought new insights into the mechanistic
knowledge of the compaction process of porous particles and
It is recommended that four mechanisms are involved justified the use of these units as an alternative model
in the compression process of granules namely – system. It has been suggested that permanent deformation
deformation, densification, fragmentation and attrition. and densification are the major mechanisms involved in the
Recently, the use of nearly spherical units, here defined as compression of spherical units.

Fig. 4: Representation of Formulation Design (researchgate.net)

VII. CHALLANGES TO DEVELOP MUPS TABLETS 26, 27

Following factors to be considered during design and direct exposure of the transmitted force by the upper
manufacture of MUPS to avoid deformation, densification, punch to lower punch. Thus influences content
fragmentation and attrition of pellets: uniformity of the final tablet.
• Robustness of coated pellets to maintain the drug release • Pellet Density: Pellets of density about 1.5 g/cm3 shows
profile after compression. faster gastric emptying than pellets with higher density of
• Compactibility of heterogeneous mass of pellets and > 2 g/cm3. Pellets with < 2 mm in diameter and < 2 g/cm3
tabletting excipients. density can pass through pyloric sphincter both in fasted
• Mechanical strength of compacted tablets for further and fed state which is similarto liquids in terms of gastric
processing such as film or functional. emptying.
• Coating and packing. • Pellet core and Core material: Pellets should have low
surface to volume ratio as this may result in a decreased
A. Solutions to overcome challenges in MUPS 28-31 area of contact between the particles as they consolidate.
• Granulation: The tabletting mixture with good flow and Infavor of this, pellet core should have some degree of
narrow particle size distribution prevent de-mixing of plasticity to have deformation in shape during
pellets and extra-granular material. In case of big sized compression without any damage to the coated film. An
coated particles, size adaptation (managed by extensive studyhas been carried out on microcrystalline
granulation) may be considered. cellulose by many researchers both as powdered and
granulated forms, and revealed that microcrystalline
• Pellet shape: The shape of the pellets should be spherical
cellulose shows plastic deformation during compression
or nearly spherical for good uniform distribution. A more
and offers better protection to the coated particles as
deviation in spherical shape does not result of
powder and granules. Core material should not be too
characteristic release due to flaws and cracks during
hard eg. Dicalcium Phosphate pellets, which obstructs
compression.
the flow of pellets. In such case, compression force
• Pellet size: The size of the coated pellets can be shows impact on the surface and results in deformation of
maximum upto 2 mm to withstand compression pressure. the surface and altersthe release characteristics.32
Large sized pellets cause rupture to the coating of pellets
due to segregation with tabletting excipients and there by

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Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
• Porosity: Porosity of pellets plays a major role in • Extra-granular material and cushioning agents: Film
compression thereby relates to deformation. The stability is influenced by extragranular material during
deformation of pellets was much in favor of medium and compression. Sharp-edged and abrasive crystalline
high porous pellet because of high porous nature pellets materials may damage the coating as compression
become denser due to the applied compression force and force increases. This alters the drug release
forms as deformed coherent units due to the non characteristics after compaction into tablets. Type and
interfering excipients. Compaction of less porous pellets amount of thecoating agent, selection of additives like
results in significant increase in the release rates of the plasticizers, use of cushioning excipients and rate of
drug which is due to comparatively low densification and pressure applied must be monitored carefully to maintain
deformation. The excipients used should not interfere the drug release properties of the sub units helps in the
with the pellets which alter the drug release profile. The protection of the film. Cushioning agents are waxy in
extragranular material must form closest packing with nature take up the pressures of compaction by re-
the deformed pellets.33 arranging themselves within the tablet structure or by
• Polymer coating and Film flexibility: Polymers widely preferentially getting deformed and/or fractured thereby
used in attaining specific release profiles are cellulose provides protection to the coated pellets. The best choice
derivatives and polyacryls. Cellulose and its derivatives of cushioning agent is polyethylene glycol preferably
like HPMC, HPMCP forms hard and brittle films that polyethylene glycol 6000. Cushioning pellets are
fractures during compression whereas polyacryls and normally more porous and soft compared to coated drug
copolymers of acrylics form flexible film deforms easily pellets and normally made of excipients which are used.
on compression. Plasticizers like triethyl citrate, triacetin The drug pellets-to-cushioning excipient(s) ratio is very
and polyethylene glycol also helps in the formation of critical in preventing coatingfilm damage – a ratio of 1:3
flexible films. During compression a highly flexible film or 1:4 is considered most suitable 35, 36
ensures elastic properties and prevents cracking of • Electrostatic charges: Development of an electrostatic
coating. Polymers like Eudragit along with plasticizers charge on the pellet surfacescan interfere with their flow
triethyl citrate provide greater flexibility to the film in during tablet compression cycle. This problem is usually
required quantity. solved by adding talc, which acts as a glident.37, 38 During
• Selection of Solvents: Both aqueous and non-aqueous development of multiparticulate tablets comparative
coatings can be done. Though aqueous coating is eco- dissolution tests should be conducted to identify the
friendly, a certain drawbacks such as degradation of the possible differences between the release rates of the
drug due to entrapped moisture; when pellets are cured uncompressed tabletting mixture versus the tablets. In
for more time to evaporate moisture, the temperature also order to ensure reproducible drug releases the difference
results in degradation. Whereas, non-aqueous coatings between the two dissolution profiles should not exceed
show thixotropy of polymer solution as sol-to-gel; helps 10%.
to coat the polymeric solutionand the solvent evaporate
much earlier than aqueous solvents.33 VIII. MARKETED PRODUCTS OF MUPS
• Mechanical resistance: Film flexibility provides Losec MUPS is the second highest selling
mechanical stability to pellets during compaction. During pharmaceutical drug product in Sweden in the year 2002.
compression, high mechanical resistance support film Another patent is of European Patent Office by Astrazeneca
integrity by preventing deformation of pellets. Larger EP 723437 for Nexium and Losec for compression of proton
particle size supports mechanical stability and leads to pump inhibitor to tablets for MUPS into the market. Various
less interparticle contacts which also support less film marketed products are tabulated in Table I.
damages.34
• Porosity Coating thickness: The thickness of coating
layer is related to mechanical resistance of pellets during
compaction. Greater thickness supports elastic properties,
whereas below a certain thickness even highly flexible
films tend to break. The mannerin which deformation of
the coated pellets occurs during compaction alters the
thickness of the coating layer which has an impact on the
release profile of the drug.

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Volume 7, Issue 5, May 2023 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Table 1: Marketed Products of MUPS(researchgate.net)
Product Company Drug Therapeutic Formulation
Category type
Losec MUPS Astra Zeneca Omerprazole Antiulcer Antiulcer
Magnesium
Esomeprazole Astra Zeneca Esomeprazo Antiulcer Antiulcer
Le Magnesium
Troprol XL Astra Zeneca Metoprolol Antihypertensive Extended release
tartrate
Prevacid SoluTab Takeda Lansoprazole Antiulcer Delayed release
Theodur Key Theophylline Antiasthmatic Extended release

IX. FUTURE DIRECTIONS 1997. p. 19-24.

[6.] Max S. Watson, Caroline Lucas, Andrew Hoy. ,
There are numerous challenges in developing a MUPS Oxford Hand book of Palliative care. , pp. xxii.
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a significant role because Pellet- released active ingredients Release Pellet-Based Tablet System for the Delivery
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