GASTRO RETENTIVE DRUG DELIVERY

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Presentation Transcript

Slide 1:

GASTRORETENTIVE DRUG DELIVERY SYSTEM NIRANJAN UPADHYAY. M.PHARMA 1 ST YR. PHARMACEUTICS PREPARED BY-

CONTENT:

CONTENT INTRODUCTION APPROACHES. FACTORS AFFECTING GASTRIC RETENTION. MARKETED EXAMPLES REFERENCES.

INTRODUCTION:

INTRODUCTION Gastroretentive drug delivery is an approach to prolong gastric residence time. Gastroretentive dosage forms can remain in the gastric region for long periods and hence significantly prolong the gastric retention time (GRT) of drugs. Prolonged gastric retention can be achieved by using floating, swelling, bioadhesive, or high-density systems. Therapeutic advantages. Patient compliance.

NEED OF GRDDS.:

NEED OF GRDDS. To increase retention period of drug in GIT. To prolong contact time for absorption. To increase bioavailability.

DRUGS WHICH REQUIRE GRDDS:

DRUGS WHICH REQUIRE GRDDS Drugs that having low absorption window. Drugs that having low solubility. Drugs for local effect like antacids and h- pyroli infection.

Slide 6:

SR GRDDS Absorption Window

Advantages:

Advantages Reduce dosing frequency. Better patient compliance and convenience. Reduce GI side effects. Less fluctuation in plasma drug level. Improved efficacy. More uniform drug effect. Treatment of gastrointestinal disorders such as gastro- esophageal reflux. Controlled delivery of drugs.

Limitations :

Limitations Require high level of fluids in the stomach. Buoyancy to float. Floating systems are not feasible for drugs that have solubility or stability problems in gastric fluid. Drugs which are well absorbed along the entire GI tract and which undergoes significant first- pass metabolism, may not be desirable candidates for GRDDS. Drugs that are irritant to gastric mucosa are not suitable for GRDDS.

Gastric emptying :

Gastric emptying This is a series of events that cycle through the stomach and small intestine every 1.2 to 2hrs.

FACTORS AFFECTING GASTRIC RETENTION.:

FACTORS AFFECTING GASTRIC RETENTION. Density of dosage form. Size of dosage form. Food intake and nature of food. Effect of gender. Posture. Age.

DEVLOPMENT APPROACHES:

DEVLOPMENT APPROACHES High density system. Floating systems. Expandable systems. Mucoadhesive or bioadhesive systems. Pharmacological agents that delay gastric emptying.

High density systems:

High density systems It includes High density pellets Low density pellets (floating delivery system) Low density system density< 1 High density system Density > 1

High density pellets:

High density pellets The density of GI fluid is around 1.4 g/cc. Use of drug pellets having density greater than this results in prolonged GI residence that is unaffected by food. Iron oxide, titanium dioxide, barium sulfate have been used to increase density of drug pellets. The drug is coated on the heavy core and then covered by a diffusion controlled membrane.

Slide 14:

drug High density core diffusion controlled membrane

Slide 15:

HIGH DENSITY

Floating systems:

Floating systems Single-unit floating dosage system. 1) Noneffervescent systems. 2) Effervescent (gas-generating) systems. Multiple-unit floating dosage system 1) Noneffervescent systems. 2) Effervescent (gas-generating) systems. 3) Hollow microspheres. Raft-forming systems.

Slide 17:

FLOATING LOW DENSITY APROACH

Non effervescent systems:

Non effervescent systems These systems contain one or more hydrocolloids and are made into a single unit along with drug and other additives. When coming in contact with water, the hydrocolloids at the surface of the system swell and facilitate floating. The coating forms a viscous barrier, and the inner polymer slowly gets hydrated as well, facilitating the controlled drug release. Such systems are called “ hydrodynamically balanced systems.

The polymers used in this system:

The polymers used in this system Hydroxypropylmethylcellulose. Hydroxyethylcellulose. Hydroxypropylcellulose. Sodium carboxymethylcellulose. Agar. Alginic acid.

Effervescent (gas-generating) systems:

Effervescent (gas-generating) systems

Floating system with infalatable chamber:

Floating system with infalatable chamber MICROPOROUS RESERVIOR AA MULTILAYER FILM A I R Sealing at periphery

Multiple unit floating system:

Multiple unit floating system Floating pills

Raft-Forming Systems :

Raft-Forming Systems This system is used for delivery of antacids treatment of gastrointestinal infections and disorders. The mechanism involved in this system includes the formation of a viscous cohesive gel in contact with gastric fluids,wherein each portion of the liquid swells, forming a continuous layer called raft. This raft floats in gastric fluids because of the low bulk density created by the formation of CO 2 .

Hollow microspheres:

Hollow microspheres floating properties, because of central hollow space inside the microsphere. The general techniques involved in their preparation include simple solvent evaporation, and solvent diffusion and evaporation. Polycarbonate, cellulose acetate, calcium alginate, agar and low methoxylated pectin are commonly used as polymers in preparation of hollow microsphere. Buoyancy and drug release are dependent on quantity of polymer, the plasticizer–polymer ratio and the solvent used.

Expandable systems:

Expandable systems Gastric emptying of dosage form can be delayed in the fed state if its size is greater than 2 mm. Retention of the system can be achieved by expandable approach.

Slide 27:

EXPANDABLE APPROACH SWELLING SYSTEMS POLYMERIC ENVELOPE TINY PILLS in MATRIX DRUG

Slide 28:

EXPANDABLE EXPANDABLE EXPANDABLE EXPANDABLE APPROACH

Bioadhesive DDS:

Bioadhesive DDS It is conceptulized on the basis of GI self protecting mechanism. Mucin constantly found at surface epithelium, have a property of adhesion. Polymers containing carboxy groups eg . Poly acrylic polymers are serve as bioadhesive polymers. - carbopol , sod. Alginate, HPMC, tragacanth etc.

Mechanism:

Mechanism Drug incorporated in mucoadhesive polymer is adhere to surface epithelium or mucin . Mucoadhesive layer slowly release drug which can diffuse through epithelium for absorption.

Pharmacological agents that delay gastric emptying. :

Pharmacological agents that delay gastric emptying. Drugs like anti- muscarinic agents reduces GI motility and thereby increase retention of drug in GIT with improved bioavailability Eg . Propenthelin , a anti-muscarinic drug improves retention B ioavailability of hydrochlorthiazide .

Slide 33:

MARKETED PRODUCTS Brand Name Drug (dose) Company Madopar ® Levodopa (100 mg), Benserazide (25 mg) Roche, USA Valrelease ® Diazepam (15 mg) Hoffman LaRoche, USA Liquid Gaviscon ® Al(OH) 3 + MgCO 3 GlaxoSmithKlein, India Topalkan ® Liquid Al – Mg antacid Pierre Fabre Drug, France Almagate Flotcoat ® Al – Mg antacid Conviron ® Ferrous sulfate Ranbaxy, India Cifran OD ® Ciprofloxacin (1 g) Ranbaxy, India Cytotec ® Misoprostal (100/200  g) Pharmacia, USA

REFERENCES:

REFERENCES Indian journal of pharmaceutical education and research, Vol-43(2),april-jun,2009. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gatroretentive dosage forms: Overview and special case of Helicobacter pylori. J Control Release. 2006;111:1-18. Hari Vardhan Reddy L and Murthy RSR. Floating Dosage Systems in Drug Delivery. Critical Revises in Therapeutic Drug Carrier Systems. 2002;19(6):553-585.

Slide 35:

Novel drug delivery system, Yie W. chien , second edition, vol-50 Shweta A, Javed A, Alka A, Roop K, and Sanjula B. Floating drug delivery systems: a review. AAPS PharmSciTech . 2005;6 (3) Article 47. Ecyclopedia of Pharmaceutical Technology. Julan UD. Floating Drug Delivery Dystem : An Approach to Gastroretension . Latest Reviews . 2007;5(1).