Multi Particulate Drug Delivery System

8/2/2019 Multi Particulate Drug Delivery System

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MULTIPARTICULATE DRUG DELIVERY SYSTEMMULTIPARTICULATE DRUG DELIVERY SYSTEM

BY

Miss. JASMIN M. JAIN

(T. Y. B. Pharm)

GUIDE

Mr. HEMANT H. GANGURDE

(M. Pharm)

DEPARTMENT OF PHARMACEUTICS

S. N. J. B.S S.S.D.J COLLEGE OF PHARMACY, CHANDWAD.


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DRUGDRUG DELIVERYDELIVERY SYSTEMSYSTEM

Drug delivery is the method or process of administering a pharmaceutical

compound to achieve a therapeutic effect in humans or animals. Most common

routes of administration include the preferred non-invasive peroral (through the

mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and

rectal) and inhalation routes.

The choice of the route, however, depends on

a) Physical & chemical characters of the drugs

b) Effect desired

c) Urgency and seriousness of the condition.

Local delivery

If the target receptor is external or easily accessed then local delivery of the

medication can be a feasible and effective approach.

Systemic delivery

When the target receptor cannot be easily accessed systemic


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MULTIPARTICULATE DRUG DELIVERY SYSTEM (MPDDS)MULTIPARTICULATE DRUG DELIVERY SYSTEM (MPDDS)

Multiparticulate dosage forms are pharmaceutical formulations in which the active

substance is present as a number of small independent subunits with diameter of

0.05-2.00 mm. They provide many advantages over single unit systems because of

their small size. Multiparticulate drug delivery is less dependent on gastric

emptying, resulting in less inter and intra subject variability in GI transit time.

MPDDS applies specially to multiple particles such as pellets, beads, microspheres,

microcapsules.

OBJECTIVEOBJECTIVE OFOF MPDDSMPDDS

Sustain release or prolong release medication Taste masking

Improve stability

Increase solubility or dispersability

Increase therapeutic efficiency


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ADVANTAGES OF MPDDSADVANTAGES OF MPDDS

It minimizes the risk of local irritation.

It results in shorter lag time for Floating Drug Delivery Sysyem

It avoids fortuitous (all or none) emptying process.

It reduces patient-to patient variability i.e. inter-subject variability.

It provides greater flexibility to the formulators.

It spreads more evenly in the GIT, thus improving the therapeutic

efficacy of the medicinal agents.

Lower Tendency of Dose Dumping

Greater stability of Chemically incompatible drugs

Ease of Design of Controlled Released Formulation containing more than

one drug

Improved Elegance, Product identification, & Patient compliance


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DISADVANTAGE OF MPDDSDISADVANTAGE OF MPDDS

Low drug loading

Proportionally higher need for excipients

Lack of manufacturing reproducibility and efficacy

Large number of process variables

Multiple formulation steps

Higher cost of production

Need of advanced technology

Trained/skilled personal needed for manufacturing


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MechanismMechanism ofof DrugDrug ReleaseRelease fromfrom MPDDSMPDDS

Three delivery systems dominate todays market of oral CR products: matrix,

reservoir, and osmotic systems. Release mechanisms from these dosage forms

have been the subjects of extensive studies. The mechanism of drug release

from MPDDS can be occurring in the following ways:

1. Diffusion

a. Matrix system

b. Reservoir system

2. Erosion

3. Osmosis


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11.. DiffusionDiffusion :

In these types of systems, the rate-controlling step is not the dissolution rate but

the diffusion of dissolved drug through a polymeric barrier. The process of

dissolution of solid particles in a liquid, in the absence of reactive or chemicalforces, consists of two consecutive steps:

a. Solution of the solid to form a thin film or layer at the solid liquid interface

called as the Stagnant film or diffusion layer which is saturated with the

drug; this step is usually rapid

b. Diffusion of the soluble solute from the stagnant layer to the bulk of the

solution; this step is slower & is therefore the rate determining step in drug

dissolution

The 2 types of diffusion controlled systems are:

a. Matrix System

b. Reservoir System

a. Matrix System

A matrix system consists of active and inactive ingredients that are

homogeneously mixed in the dosage form. We divide matrix systems into two

categories, based on rate-controlling materials like Hydrophobic and

Hydrophilic


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Hydrophobic matrix systems

As the term suggests, the primary rate controlling components of a hydrophobic

matrix are water insoluble in nature. Eg: waxes, glycerides, fatty acids, ethyl-

cellulose & methacrylate copolymers.

Hydrophilic matrix systems

The primary rate-controlling ingredients of a hydrophilic matrix are polymers

that would swell on contact with the aqueous solution and form a gel layer on the

surface of the system. Eg: HPMC ,polyethylene oxide , HPC, xantham gum.

Marketed products of Matrix SystemMarketed products of Matrix System

Products Active ingredient(s) Manufacturer

OPANA ER tab Oxymorphone HCL Endo

Seroquel XR tab Quetiapine fumarate Astrazeneca


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b. Reservoir System

A typical reservoir system consists of a core (the reservoir) and a coating

membrane (the diffusion barrier). The core contains the active ingredients and

excipients, whereas the membrane is made primarily of rate-controlling polymer(s).

Marketed Products:Marketed Products:

Metadate CD and Ritaline LA

22.. ErosionErosion

In this system, drug is dispersed throughout the polymer, and the rate of drug

release depends on the erosion rate of the polymer. However, some diffusion of the

drug from the polymer may also occur. In a surface eroding system, the drug

release rate is proportional to the polymer erosion rate and can be controlled by

changing the system thickness and total drug content. Surface erosion eliminates

the possibility of dose dumping, thus improving device safety.


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3. OsmosisOsmosis

The system is composed of a core tablet surrounded by a semipermeable

membrane coating having a 0.4mm diameter hole. The core tablet has 2 layers,

one containing the drug (the active layer) & the other containing a polymeric

osmotic. agent (a push layer). The rate of inflow of water & function of the tablet

depends on an osmotic gradient between the contents of the two-layer core & the

fluid in the GIT.


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CLASSIFICATIONCLASSIFICATION OFOF MPDDSMPDDS

Depending upon its size and structure MPDDS are classified as follows:

1. Drug crystals

2. Minitablets

3. Microcapsules

4. Nanoparticles

5. Microsphere

a. Spheronised granules (pellets)

i. Extrusion

ii. Spheronization

iii. Melt extrusion

b. Drug-loaded Non-pariels (pellets)/Drug layering


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11.. DRUGDRUG CRYSTALSCRYSTALS

Drug Crystals, of appropriate size and shape can be coated directly with a

modified release film coating.

22.. MINIMINI TABLETSTABLETS

Minitabs are small tablets with a diameter typically equal to or less than 3mm that

are typically filled into a capsule, or occasionally, further compressed into larger

tablets. The minitablets may have any shape convenient to the skilled person for

designing tablets i.e.Spherical, Cylindrical, Biconvex round, Flat-faced round. The

minitablets may be uncoated, or coated with one or more layers of coating.

Figure 1: Minitablet delivered as a tablet (a) or a capsule (b).


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33.. MICROCAPSULESMICROCAPSULES

In this the drug is centrally located within the polymeric shell of finite thickness

and release may be controlled by dissolution, diffusion or both. Steroids, peptides

and anti-neoplastics have been successfully administered parenterally by use of

controlled release microcapcules.

4. NANOPARTICLES4. NANOPARTICLES

The National Cancer Institute, under the National Nanotechnology Initiative

Program, recently defined nano-sized drug carriers as those which are typically

300 nm or smaller in size. The nanoparticles are also called as Nanospheres or

Nanocapcules depending upon whether the drug is in a polymer matrix or

encapsulated in a shell. The main objective of developing nanosized drug carriers

is to enhance the therapeutic potential of drugs so that they are less toxic and more

effective.


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55.. MICROSPHERESMICROSPHERES

Microspheres are small discrete spherical particles, with

diameters in the micrometer range(typically 1m to1000m(1mm).Microsphere are sometimes referred to as microparticles.

Polyethylene and polystyrene microspheres are two most common types of

polymer microspheres.

i. Spheronized Granules(Pellets)

Pellets are agglomerates of fine powders or granules of bulk drugs and excipients.

They consist of small, free-flowing, spherical or semi spherical solid units,

typically from about 0.5mm to 1.5 mm, and are intended usually for oral

administration. Implants of small, sterile cylinders formed by compression from

medicated masses are also defined as pellets in pharmacy.


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Mechanism of granule formation

Different theories have been postulated related to the mechanism of formation

and growth of pellets. The mechanism of pellet formation and growth, the

following steps were proposed:

nucleation, coalescence, and layering and abrasion transfer.

Figure 2: Pellet growth mechanisms (1) Nucleation, (2) coalescence,

(3) layering and abrasion transfer


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MethodsMethods forfor preparingpreparing pelletspellets

Compaction and drug layering are the most widely used pelletisation

techniques in pharmaceutical industry, extrusion and spheronization is the

most of the compaction techniques popular method.

Some of the methods used are:

i. Extrusion- technique

ii. Spheronization-technique

iii. Hot-melt extrusion

i. Extrusion Technique

Extrusion is a multiple step compaction process comprising dry mixing of the

ingredients with excipients, wet granulation of the mass, extrusion of the

wetted mass, charging the extrudates into the spheroniser to produce aspherical shape, drying the wet pellets in a dryer and, finally, screening to

achieve the required size distribution.


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Equipments used in Extrusion technique (Extruders):

A variety of extruders are currently in the market, differing in design features

and Operational principles. These can be classified as

1. Screw-fed extruders

2. Gravity-fed extruder

3. Rotary-cylinder extruders

4. RAM extruders

ii. Spheronizer Technique

A spheronizer, known as Marumizer, consists of a static cylinder or stator and

a rotating friction plate at the base. The stator can be jacketed for temperature

control.

iii. Hot Melt Extrusion (HME):

Melt extrusion is the process which can be clubbed under extrusion

spheronization whereby a drug substance and excipients are converted into a

molten or semi molten state and subsequently shaped using appropriate

equipment to provide solid spheres or pellets.


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The HME offers some advantage over a wet mass extrusion and

spheronization method:

1. It is a simple, efficient and continuous process requires.

2. It does not require a lengthy drying stage3. The absence of water may prevent drug degradation

4. It produces a spherical shape pellets with narrow range particle size

distribution.

a) Reduce the loss of coating material

ii. DrugDrug--loadedloaded NonNon--pareilspareils (pellets)(pellets)Spherical particles about 1mm in diameter consisting primarily of sucrose

and starch called non-pareils which are available in the market. Following

techniques can be used to get drug loaded non pareils. The different methods

used for preparation of Drug loaded Non-pareils (pellets) are:

1. Drug layering2. Miscellaneous methods

a.Balling

b.Compression

c.Cryopellitization

d.Globulation.


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EvaluationEvaluation && characterizationcharacterization ofof MultiparticulatesMultiparticulates

A. Size distribution

B. Shape and surface roughness

C. Surface area

D. Porosity

E. Density

F. Friability

G. Content Uniformity

H. Tensile strength


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MPDDS TECHNOLOGIES WITH EXAMPLESMPDDS TECHNOLOGIES WITH EXAMPLES

TECHNOLOGIES COMPANIES MECHANISM / PRINCIPLE

OF RELEASE

Diffucaps

Orbexa

Eurand SR and Pulsatile Release

Film diffusion via polymer

coating

SODAS / CODAS Elan Sustained and/or Pulsatile

Release

SDD Bend Research Spray-dried dispersion beads /

Enteric Release

MARKETED FORMULATIONSMARKETED FORMULATIONS

DRUG BRAND COMPANIES

Morphine sulfate Avinza King

Carbamazepie Carbatrol Shire,US

Equetro ER Validus

Carvedilol Coreg CR GSK

Dexmethylphenidate Focalin XR Novartis


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REFERENCESREFERENCES

a) Sahoo SK, Jain TK, Reddy MK, and Labhasetwar V. Nano-Sized Carriers for

Drug Delivery, NanoBioTechonology: Bio-Inspired Devices and Materials ofthe Future: 329

b) Jain KK. Drug Delivery System. 1st Edition, Basel: Jain Pharma Biotech

Publications. Switzerland: 30-31

c) Aulton ME. Pharmaceutics, The science of dosage form design. 2nd edition.

Edinburgh: Churchill Livingstone.2002: 374-379

d) Florence AT and Attwood D. Physicochemical principles of pharmacy. 4th

edition. London: Pharmaceutical Press. 2006

e) Patrick GL. An Introduction to Medicinal Chemistry. 3rd edition, Oxford:

Oxford University Press. 2005

f) Laila FA, Chandran S. Multiparticulate Formulation Approach to colon

specific drug delivery: current perspectives. J. Pharm Sci, 2006, 9(3): 327-38g) Shah NH. Multi-Particulate Dosage Form for Oral Controlled Release:

Development Considerations. Hoffmann La-Roche. In

h) Shaji J, Chadawar V, Talwalkar P. Multiparticulate Drug Delivery System.

The Indian Pharmacist. June 2007, 6(60): 21-28.


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Multi Particulate Drug Delivery System