3INTRODUCTION• Oral drug delivery is widely used in pharmaceutical field to treat the diseases.• Some drugs are absorbed at specific site only ,these require release at that specific site.• Gastro retentive drug delivery(GRDDS) is one of the site specific drug delivery for the delivery of the drugs at stomach.• It is obtained by retaining dosage form into stomach and drug is being released at controlled manner at specific site
4APPROPRIATE CANDIDATE DRUGS FORGRDDS• Drugs acting locally in the stomach. E.g. Antacids and drugs for H. Pylori viz., Misoprostol.• Drugs that are primarily absorbed in the stomach. E.g. Amoxicillin• Drugs that is poorly soluble at alkaline pH. E.g. Furosamide, Diazepam, Verapamil, etc.• Drugs with a narrow absorption window. E.g. Cyclosporine, , Levodopa, Methotrexate etc.
5• Drugs which are absorbed rapidly from the GI tract. E.g. Metronidazole, tetracycline.• Drugs that degrade in the colon. E.g. Ranitidine, Metformin.• Drugs that disturb normal colonic microbes E.g. antibiotics against Helicobacter pylori.
6ADVANTAGES• Enhanced bioavailability• Sustained drug delivery/reduced frequency of Dosing• Targeted therapy for local ailments in the upper GIT• Reduced fluctuations of drug concentration• Improved selectivity in receptor activation• Reduced counter-activity of the body
7ADVANTAGES• Extended effective concentration.• Minimized adverse activity at the colon.
8LIMITATIONS• The drug substances that are unstable in the acidic environment of the stomach are not suitable candidates to be incorporated in the systems.• These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently.
9• Not suitable for drugs that have solubility or stability problem in GIT.• Drugs which are irritant to gastric mucosa are also not suitable.• These systems do not offer significant advantages over the conventional dosage forms for drugs, which are absorbed throughout GIT.
10 APPROACHES FOR PROLONGING THE GASTRIC RESIDENCE TIME HD S F• High-density systems. S (HDS) S A S S• Floating systems. (FS)• Swelling and expanding systems. (SS)• Mucoadhesive & Bioadhesive systems. (AS)
12HIGH DENSITY SYSTEM• Gastric contents have a density close to water ( 1.004 g cm−3). When the patient take high-density pellets , they sink to the bottom of the stomach where they become entrapped in the folds of the antrum and withstand the peristaltic waves of the stomach wall.• A density close to 2.5 g cm−3 seems necessary for significant prolongation of gastric residence time.• Barium sulphate , zinc oxide, iron powder, and titanium dioxide are examples for excipients used.
13FLOATING DRUG DELIVERYThese have a bulk density lower than the gastriccontent. They remain buoyant in the stomach for aprolonged period of time, with the potential forcontinuous release of drug. They Include: Hydrodynamically balanced systems (HBS) Gas-generating systems Volatile liquid/ vacuum containing systems Raft-forming systems Low-density systems
14GAS GENERATING SYSTEMS• Carbonates or bicarbonates, which react with gastric acid or any other acid (e.g., citric or tartaric) present in the formulation to produce CO2 , are usually incorporated in the dosage form, thus reducing the density of the system and making it float on the media.
15MATRIX TABLETS• Single layer matrix tablet is prepared by incorporating bicarbonates in matrix forming hydrocolloid gelling agent like HPMC, chitosin, alginate or other polymers and drug.• Bilayer tablet can also be prepared by gas generating matrix in one layer and second layer with drug for its SR effect.• Triple layer tablet also prepared having first swellable floating layer with bicarbonates, second sustained release layer of drug and third rapid dissolving layer of bismuth salt.
16INFLATABLE GASTROINTESTINALDELIVERY• System is incorporated with an inflatable chamber which contains liquid ether -gasifies at body temperature to cause the chamber to inflate in stomach.• Inflatable chamber is loaded with a drug reservoir which can be a drug, impregnated polymeric then encapsulated in a gelatin capsule.
17INTRAGASTRIC OSMOTICALLY CONTROLLEDDDS Comprised of both an osmotic pressure controlled drug delivery device and an inflatable floating support in a biodegradable capsule. In stomach, the capsule quickly disintegrates and release the intragastric osmotically controlled drug delivery device . Inflatable support forms a deformable hollow polymeric bag containing liquid that gasifies at body temperature to inflate the bag.Consists of 2 compartments:• Drug reservoir• Osmotically active compartment.
18INTRA-GASTRIC FLOATING GASTROINTESTINALDRUG DELIVERY SYSTEMS• System can be float by flotation chamber, which may be vacuum or filled with air or a harmless gas• Drug reservoir is encapsulated inside a microporous compartment
19HYDRODYNAMICALLY BALANCED SYSYTEMS Prepared by incorporating a high level(20-75%w/w) gel- forming hydrocolloids. E.g.:- Hydoxyethylcellulose, hydroxypropylcellulose, HPMC & Sod. CMC into the formulation and then compressing these granules into a tablets or capsules. It maintains the bulk density less than 1.
20RAFT FORMING• This system is used for delivery of antacids and drug delivery for 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, forming a continuous layer called raft.
21HOLLOW MICROSPHERES• Polymers used commonly: Polycarbonates, Cellulose acetate, Calcium alginate, Eudragit S, agar and methoxylated pectin etc.
22ALGINATE BEADS SUPERPOROUS HYDROGELS• Prepared by dropping sodium • Swellable agents have pore alginate solution into aqueous size ranging between 10nm to solution of calcium chloride, 10µm. causing the precipitation of • Superporous hydrogels will calcium alginate swell more than the swelling• Freeze dry in liquid nitrogen at ratio 100,This is achieved by -40oc for 24h. co-formulation of a hydrophilic particulate• Beads-spherical and 2.5 mm in material, and Ac-Di-Sol diameter. (crosscarmellose).
23 EXPANDABLE SYSTEMS1.UNFOLDED SYSTEMS 2.SWELLABLE SYSTEMS The swelling is usually results from osmotic absorption of water. The device gradually decreases in volume and rigidity as a result depletion of drug and expanding agent and/or bioerosion of polymer layer, enabling its elimination.
24MUCOADHESIVE SYSTEMS• The basis of mucoadhesion is that a dosage form can stick to the mucosal surface by different mechanisms.• Examples for Materials commonly used for bioadhesion are poly(acrylic acid) (Carbopol®, polycarbophil), chitosin, Gantrez® (Polymethyl vinyl ether/maleic anhydride copolymers), cholestyramine, tragacanth, sodium alginate
25MAGNETIC SYSTEM •Based upon the principle that dosage form contains a small internal magnet ,and a magnet placed on the abdomen over the position of stomach can enhance the GRT.
26Marketed Products of GRDDSBrand name Delivery system Drug (dose) Company nameValrelease® Floating capsule Diazepam (15mg) Hoffmann-LaRoche, USAMadopar® HBS Floating, CR capsule Benserazide (25mg) and L- Roche Products,(Prolopa® HBS) dopa (100mg) USALiquid Gaviscon® Effervescent Floating Al hydroxide (95 mg), Mg GlaxoSmithkline, liquid alginate Carbonate (358 mg) India preparationsTopalkan® Floating liquid alginate Al – Mg antacid Pierre Fabre Drug, Preparation FranceConviron® Colloidal gel forming Ferrous sulphate Ranbaxy, India FDDSCytotech® Bilayer floating capsule Misoprostol (100μg/200μg) Pharmacia, USACifran OD® Gas-generating floating Ciprofloxacin (1gm) Ranbaxy, India form
27CONCLUSION• Gastro retentive drug delivery systems have emerged as a current approache of controlled delivery of drugs that exhibit an absorption window.• All these drug delivery systems have their own advantages and drawbacks.• To design a successful GRDDS, it is necessary to take into consideration the physicochemical properties of the drug, physiological events in the GIT, formulation strategies, and correct combination of drug and excipients.
28REFERENCE• N K Jain. Gastroretentive drug delivery systems: Garima Chawla, Piyush Gupta and Aravind K. Bansal, editors. Progress in controlled and novel drug delivery systems.New delhi.• S.P.vyas, roop K.khar controlled drug delivery concepts and advances page no.196-217.