Recent Trade Presentation

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RECENT TRENDS INRECENT TRENDS IN

GASTRORETENTIVE MUCOADHESIVEGASTRORETENTIVE MUCOADHESIVE

MICROSPHEREMICROSPHERE

Presented by:-

Mr. Madhav S. MuleM.Pharm (Semester-3)

Department of Pharmaceutics

Guided by:-

Mr. Kshirsagar R.V.Asst. Professor

School of Pharmacy, S.R.T.M.U. NANDED

Maharashtra, India.

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Contents:Contents:Introduction.

Approaches To Gastric Retention.Muco-adhesive Systems.

Need For Mucoadhesive Microsphere.

Advantages.

Mechanism of Mucoadhesion.

Theories of Mucoadhesion.

Polymers Used In Mucoadhesive Microsphere.

Factors Affecting Mucoadhesion.

Techniques of Formulation Mucoadhesive Microspheres.

Evaluation Method of Mucoadhesive Microsphere.

Limitation of Gastroretentive Mucoadhesive System.

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IntroductionIntroduction

The control of gastrointestinal transit of orally administered

dosage forms using Gastroretentive drug delivery systems

(GRDDS) can improve the bioavailability of drugs that exhibit

site-specific absorption.

Prolonged gastric retention can be achieved by using floating,

swelling, bioadhesive, or high-density systems.

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Approaches To Gastric RetentionApproaches To Gastric Retention

Floating Systems.

Swelling and Expanding Systems .

High density systems.

Ion exchange resins.

Osmotic regulated systems.

Low density approach.

Bio/Muco-adhesive Systems.


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Floating Systems.

Floating Drug Delivery Systems (FDDS) have a bulk density lower

than gastric fluids thus remain buoyant in stomach. the system

floats on gastric contents, the drug is released slowly at a desired

rate from the system

Swelling and Expanding Systems .

These are dosage forms, which after swallowing swell to an extent

that prevents their exit from the pylorus. As a result, the dosage

form is retained in stomach for a long period of time. These

systems may be named as plug type system, since they exhibit

tendency to remain logged at the pyloric sphincter6


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Ion exchange resins.

Ion exchange resins are loaded with bicarbonate and a negatively

charged drug is bound to the resin.

The resultant beads are then encapsulated in a semi-permeable

membrane to overcome the rapid loss of carbon dioxide.

Osmotic regulated systems.

The osmotic controlled drug delivery device consists of two

components drug reservoir compartment and osmotically active

compartment. Due to Osmotic pressure microsphere floated in

Stomach.

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High density systems.

1. Gastric contents have a density close to water (~1.004).

2. A density close to 2.5g cm-3 is necessary for significant

prolongation of gastric residence time.

3. The commonly used excipients in high density system includes

barium sulphate, zinc oxide, iron powder, and titanium dioxide.

Low density approach.

In this approach, the density of pellets should be less than 1 g/ml,

so as to float the pellets or tablets in the gastric fluid and, release

the drug slowly for a longer period of time.

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Bio/Muco-adhesive Systems.

The technique involves coating of microcapsules with bioadhesive

polymer, which enables them to adhere to intestinal mucosa and

remain for longer time period in the GI while the active drug is

released from the device matrix.

The cationic chitosan polymers are pharmaceutically acceptable to

be used in the preparation of bioadhesive formulations owing to

their known ability to bind well to gastric mucosa.

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Need For Mucoadhesive MicrosphereNeed For Mucoadhesive Microsphere

Are locally active in the stomach (misoprostol, antacids antibiotics

against H.pylori).

Have an absorption window in stomach or in the upper small

intestine (L-dopa, P-aminobenzoic acid, furosemide).

Are unstable in the intestine or colonic environment (captopril).

Exhibit low solubility at high pH values (diazepam, verapamil).

Alter normal flora of the colon (antibiotics).

Absorbed by transporter mechanism (paclitaxel).


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AdvantagesAdvantages

Prolongs the residence time of the dosage form at the site of

absorption.Due to an increased residence time it enhances absorption and

hence the therapeutic efficacy of the drug.

Excellent accessibility.

Rapid absorption because of enormous blood supply and goodblood flow rates.

increase in drug bioavailability due to first pass metabolism

avoidance.

Drug is protected from degradation in the acidic environment inthe GIT.

Improved patient compliance- ease of drug administration.

faster onset of action is achieved due to mucosal surface.

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MECHANISM OF MUCOADHESIONMECHANISM OF MUCOADHESIONMucoadhesion has the following mechanism,

Intimate contact between a bioadhesive and a membrane (wetting

or swelling phenomenon).

Penetration of the bioadhesive into the tissue or into the surface

of the mucous Membrane (interpenetration).


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TTHEHEORIES OF MUCOADHESIONORIES OF MUCOADHESION

Electronic theory

Electron transfers occur upon contact of adhesive polymer with amucus glycoprotein network because of difference in their electronic

structures.

This results in the formation of electrical double layer at the interface

and provides an intimate contact between a dosage form andabsorbing tissue.

Absorption theory

After an initial contact between two surfaces, the material adheresbecause of surface force acting between the atoms in two surfaces.

Two types of chemical bonds resulting from these forces can be

distinguished as primary and Secondary chemical bond.


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Diffusion theory

The polymer chains and the mucus mix to a sufficient depth to create

a semi permanent adhesive bond.

Wetting theory

If two substrate surfaces are brought in contact with each other in the

presence of the liquid, the liquid may act as an adhesive among the

substrate surface.

Cohesive theory

The cohesive theory proposes that the phenomena of bioadhesion are

mainly due to intermolecular interaction amongst like molecule


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Polymers Used In Mucoadhesive MicrospherePolymers Used In Mucoadhesive Microsphere

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1. Hydrophilic polymers

2. Hydrogels

3. Newer second generation polymers

a. Lectins

b. Thiolated polymers

c. Polyox WSRA


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Factors Affecting MucoadhesionFactors Affecting Mucoadhesion

Physiological Factors.

Environment-related factors.

Polymer-related factors.

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Physiological Factors.

1. Molecular weight2. Concentration of active polymer

3. Flexibility of polymer chains

4. Spatial conformation

5. SwellingEnvironment-related factors.

1. PH of polymer-substrate interface

2. Applied strength

3. Initial contact time


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I. Hot Melt Microencapsulation

II. Solvent Removal

III. Hydrogel Microspheres

IV. Phase Inversion Microencapsulation

V. Solvent Evaporation

VI. Spray Drying

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Techniques of Formulation ofTechniques of Formulation of

Mucoadhesive MicrospheresMucoadhesive Microspheres


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Techniques Of Formulation OfTechniques Of Formulation Of

Mucoadhesive MicrospheresMucoadhesive MicrospheresSolvent Evaporation


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Spray Drying

E l i M h d Of M dh iE l ti M th d Of M dh i


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Evaluation Method Of MucoadhesiveEvaluation Method Of Mucoadhesive

MicrosphereMicrosphere

In-vitro drug release

In vivo drug release

In-vitro Mucoadhesivity

Determination of drug entrapment efficiency

Measurement of adhesive strength/in vitro tests

Tensile stress measurement

1. Wilhelmy plate technique

2. Novel electromagnetic force transducer

3. Shear stress measurement


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Tests to measure the adhesive strength

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1. Adhesion number

1. Particle size analysis

1. Swelling index of microspheres

1. Production Yield

1. In vitro wash-off test for microspheres

2. Falling liquid film method

3. Everted sac technique

4. Novel rheological approachOther in vivo evaluation test

1. Measurement of the residence time/in vivo techniques

2. GI Transit using radio-opaque microspheres

1. Scanning Electron Microscopy (SEM)

1. Gamma scintigraphy technique

2. Surface characterization of the mucoadhesive microspheres


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Application Of GastroretentiveApplication Of Gastroretentive

Mucoadhesive Drug Delivery SystemsMucoadhesive Drug Delivery Systems

Sustained drug delivery

Enhanced bioavailability

Site specific drug delivery

Reduced fluctuation of drug concentrations

Improved selectivity in receptor activation

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Gastroretentive Products Available InGastroretentive Products Available InThe MarketThe Market

Sr.No. Brand Name Active Ingredient

1 Cytotec Misoprostal

2 Cifran OD Ciprofloxacin

3 Oflin OD Ofloxacin

4 Madopar L-DOPA and Benserazide

5 Prolopa L-DOPA and Benserazide

6 Valrelease Diazepam

7 Conviron Ferrous sulfate

8 Topalkan Aluminum -magnesium antacid

9 Almagate FlatCoat Aluminum -magnesium antacid

10 Liquid Gavison Aluminium hydroxide, magnesium carbonate


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Limitation Of Gastroretentive MucoadhesiveLimitation Of Gastroretentive Mucoadhesive

SystemSystem

Bioadhesion in the acidic environment and high turnover of mucus may

raise questions about the effectiveness of this technique.

Not suitable for drug that may cause gastric lesions eg. Non- steroidal anti-

inflammatory drug. The mucus on the walls of the stomach is in a state of constant, resulting in

unpredictable adherence.

Drugs that are irritant to gastric mucosa are not suitable for GRDDS.

The bioadhesion system in patients with achlorhydria can be questionable

in case of swellable system, faster swelling properties are required and

complete swelling of the system should be achieved well before the gastric

emptying time. 24


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RferencesRferences

Deshpande, A. A., Shah, N.H., Rhodes, C.T., Malick, W.,

Development of a novel controlled release system for gastric

retention, Pharm. Res. 1997; 14 (6): 815-9.

Prance Tanagra, N.V.Satheesh Madhav Recent Advances In Oral

Mucoadhesive Drug Delivery Systems: A Review IJPRD , ISSN-

0974-9446.

Pandey Shivanand, Different Techniques of Formulation And

Evaluation of mucoadhesive Microspheres International Journal of

Pharma and Bio Sciences V1(2)2010. 25


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ReferencesReferences

Atyabi, F., Sharma, H.L., Mohammad, H., Fell, J. T., In-vivo

evaluation of a novel gastroretentive formulation based on ion

exchange resins, J. Control. Rel. 1996; 42: 105-13.

Vyas SP, Khar RK. Gastroretentive systems. In: Controlled drug

Delivery. Vallabh Prakashan, Delhi, India. 2006. p. 197-217.

Chawla G, Gupta P, Bansal AK. Gastroretentive drug delivery

systems. In: Jain NK. editor. Progress in controlled and novel drug

delivery systems. CBS Publishers and Distributors. New Delhi.

2004. p. 76-97. 26


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