Multiparticulate delayed release drug delivery

system

Presented By:- Guided by:

Krutika Ghungrud Dr. A.V. Chandewar
(M.Pharm, P.Hd, FIC)

Department of Pharmaceutics
PATALDHAMAL WADHWANI COLLEGE OF PHARMACY, YAVATMAL-
(M.S)445001.
Sant Gadge Baba Amravati University, Amravati.
Maharashtra(India)
1 (2017-2018)
 Content…..

Introduction

Advantages and disadvantages

objective

Pelleitization techniques

References

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Introduction
What is Multiparticulate DDS?
 In simple this can be termed as Multiparticulate
dosage form are pharmaceutical formulation in which
the active substance is present as a number of small
independent subunit.
 Multiparticulate dosage form consisting of
multiplicity of small discrete unit knows as pellets.

 The pelltes usually range in size from 0.5 –

1.5mm.

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 Why is Multiparticulate DDS?

. ●
Improve Bioavability

, ●
Increase surface area

. ●
Good transportation

●
Even distribution

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 Why is Multiparticulate DDS?
(Cont.…)

. Independent gastric emptying time

●

. ●
Improve degradation

. Reproducible pharmacokinetic data

●

●
Less chance of dose dumping

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DELAY RELEASE DRUG DELIVERY
SYSTEM

These are the dosage forms designed to release

the drug at a time other than promptly after
administration.

The goal in designing delayed or enteric coated

delivery systems is to improve the acid
sensitive drugs and reduce the gastric irritation.

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REASON FOR DELAY DRUG DELIVERY SYSTEM

The drug which have to be prepared delayed

should have been:

i) High degradation rate in stomach at acidic pH

ii) Cause gastric irritation
iii) Specific absorption site
iv) Should have local effect

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 Advantages
Advantages of delay released dosage form

To improve the chemical stability of acid-sensitive

drugs, to decrease gastric irritation and to target drug
release to the intestine.

Decreased local and systemic side effects reduced gastrointestinal

irritation.

Better drug utilization reduction in total amount of drug used.

Improved efficiency in treatment, optimized therapy and more

uniform blood concentration
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 Disadvantages
• High cost of preparation.

• The release rates are affected by various factors such

as, food and the rate transit through the gut.

•Patient may suffer from tremors therefore they have

difficulty to take tablet, powder and liquids. In dysphasia
physical obstacles and adherence to an oesophagus may
cause gastrointestinal ulceration.

• Poor patient compliance, increased chances of missing

the dose of a drug with short half-life for which frequent
administration is necessary.

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 Objectives
To achieve
improved economy
of tablets
Preparation of To achieve patient
stable and compliance due to
bioequivalent less frequency of
formulation. dosing

To optimize
To maximise the
process parameters
utilization of drug
for pellets

To conduct
compatibility study of
Drug with excipients
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 What is pelletization
Pelletization is an agglomeration process that converts fine
powders or granules of bulk drugs and excipients into small,
free flowing, spherical or semi-spherical units, referred to as
pellets

11 Fig:-Principle of solution / suspension layering.

 Pelletization Technique

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Freeze Pelletization

1)It is an advanced and a most simple technique for the

immiscible molten solid carrier/ matrix containing additives
like disintegrants, diluents, surfactants and release modifiers
with or without drug into an inert liquid column.

2) The droplets are introduced using needles or nozzles or

atomizer into the inlet column of liquid and dropped from a
certain height, so that droplets remain intact as they fall into
the liquid column. The process can be scaled-up by
increasing the number of nozzles (toseveral hundred) based
on the desired rate of production and they can be static or
vibrated electrically.
 3) size of needle gauge ranges from 16-31 depending
on the size of the pellets desired. These droplets move
either to size of the pellets desired. These droplets
move either to the top or bottom of the column
depending on their density with respect to liquid in the
column 18. Based on the movement of molten-solid
droplets, two apparatus are designed.
 

Figure :Freeze pelletizer I and II.

4) Based on the movement of molten-solid droplets, two apparatus
are designed. The former Freeze pelletizer I, with an inlet at the
top for introducing droplets and these droplets settle at the
bottom of the column as the density of the matrix droplet is more
than the liquid column. Freeze pelletizer II is used when the
carrier droplet density is less than the liquid column which has
an inlet atthe bottom and the droplets solidify at the top.

5)This technique involves less process variables and also

offers several advantages like production of non-porous
spherical pellets with narrow particle size range which are
feasible for further coatings like delayed; colon targeted
and sustained release coatings. Since the pellets are solid
at room temperature, they do not require drying .
Cryopelletization
1) It is a technique by which freeze dried or lyophilized
pellets are formed by solidifying the droplets of aqueous
or organic solutions, suspensions or emulsions using
liquid nitrogen as the fixing medium.
2)The technology was initially developed for the nutrition industry to
lyophilizeviscous bacterial suspensions. It is also used to produce
drug loaded pellets for immediate and controlled release
formulations.
3) The main advantage of this technique is production of highly
porous pellets .
4) The procedure permits instantaneous
and uniform freezing of the processed material owing
to rapid heat transfer that occurs between the
droplets and liquid nitrogen
Figure : A) Cryopelletizer B) Cryogranulator used to
form
Technosphere Insulin Pellets prior to Lyophilization
 CPS™ (Complex Perfect Spheres)
Freeze Pelletization
Pelletizing Technology

1) In the year 2000, this technology was

invented by Glatt GmbH in Binzen,
Germany; an advanced fluid bed rotorand a
direct pelletization technology for the
production of matrix type pellets and
micropellets.
2) The process equipment consists of a
modified fluid bed rotor system with a
conical shaped rotating disc and additional
devicesfor direct movement of particles.
3 ) This is a batch process suitable for drug
layering by drug solution, suspension, emulsion
etc. on starter cores as well as dry powder
layering to achieve a particular drug layer
quality

4) The layering liquid can be aqueous or organic

with or without functional compounds.

.
 ProCell™ Technology
1)This is a spouted-bed type continuous
agglomeration technology where particles
are
. fluidized in the ProCell™spouted bed
by vertical airflow process.

2) The ProCell™ Technology is a direct

granulation and pelletizing process. No
inert starting beads are required and
solutions, suspensions or emulsions
containing the API, can be processed.
3) ProCell™ Technology performs in the most
effective way when a melt of a material is
processed, as in this case neither water nor
organic solvents have to be evaporated; the
formation of granules and pellets takes place by
means of spray solidification and agglomeration.

4)The continuously arising product quantities can

befractionated online by means of a zig-zag-
sifter or offline by means of a sieving unit.
5) Drug loading is upto 100% i.e., no additional
excipients may be required for the formation of
ProCell™ particles due to the design of the process
chamber and its unique processing characteristics.
MicroPX™ Fluid BeTechnology
1) It is a continuous fluid bed pelletizing technology where
aqueous-based liquids can be processed for this novel
pelletization process – resulting in matrix type, onion-like
micropellets by spray solidification and agglomeration
2) For fluid be technology GPCG instrument is use
3) API, pharmaceutical binder(s) and other functional
ingredients are contained in a spraying liquid (solution,
suspension or emulsion) which is fed into the MicroPx™
process via spray guns.
4) The process is a high-through put, cost effective process
as the product losses are minimal due to the recirculation of
the material into the ongoing process.
 Reference
4. Gibaldi M. Biopharmaceutics and clinical pharmacokinetics.
Lea and Febiger, Philadelphia, Third Edition 1984, pp. 67-69

5. Palsson BO, Wheatley TA and Dressman JB. Mechanism of

release from pellets coated with an ethylcellulose based film J
Cont Rel.1990;14:, pp. 203-213.

6. Ghebre-Sellassie: Pellets: A General Overview. Pharmaceutical

Pelletization Technology, Marcel Dekker, First Edition 1989; pp,
54-59

7. Melia C, Washington N and Wilson GC. Multiparticulate

Controlled Release Oral Dosage Forms. Scottish Academic Press
Ltd; First Edition 1994.

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