highly used drug delivery system

1. GASTRO-RETENTIVE
DRUG DELIVERY SYSTEM
ANKIT KUMAR MALIK
M.PHARMACY 1st SEMESTER
DEPARTMENT OF PHARMACEUTICS
SPER JAMIA HAMDARD
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2. CONTENT
1. INTRODUCTION
2. REVIEW OF STOMACH
3. FACTORS AFFECTING GRDDS
4. GASTRO-INTESTINAL DYNAMICS
5. STRATIGIES FOR DELAYING DRUG TRANSIT THROUGH GIT
6. TYPES OF GASTRO-RETENTIVE DOSAGE FORM
7. ADVANTAGES AND DISADVANTAGES OF GRDDS
8. EVALUATION OF GRDDS
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3. INTRODUCTION
 Oral administration is the most convenient, preferred and predominant
means of drug delivery to the systemic circulation.
 Gastro-retentive drug delivery system(GRDDS) is an approach to prolong
gastric residence time.
 GRDDS is for targeting site-specific drug release in the upper
gastrointestinal tract (GIT) for local or systemic effects.
 Gastro-retentive dosage forms can remain in the gastric region for long
periods and hence significantly prolong the gastric retention time (GRT) of
drugs.
 GRDDS can improve the controlled delivery of drugs that have an
absorption window by continuously releasing the drug for a prolonged
period of time before it reaches its absorption site.
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4. Review of stomach
Proximal part made
of fundus and body acts as a
reservoir for undigested
Materials.
Antrum(pylorus) is the main site for
mixing motions and acts as a pump
for gastric emptying by propelling
actions.
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5. Gastro retention is done for:
 Drugs that absorb from stomach (Levodopa, Furosemide).
 Acting locally in stomach (Antacids, Antiulcer and Enzymes).
 Antibiotic therapy.
 Poorly soluble at alkaline pH .( Diazepam, Salbutamol).
 Degrade in colon. (Captopril, Ranitidine, Metronidazole).
 Improving Bioavailabilty .
 Reduce drug wastage.
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6. Gastric retention is unsuitable for:
 Drugs having limited acid solubility(Phenytoin).
 Unstable in gastric conditions( Erythromycin).
 Extensive first pass metabolism.
 Drugs intended for selective release in the colon ( 5- amino salicylic
acid and corticosteroids).
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7. Factors affecting gastric retention of
dosage forms
1. Density of the dosage form
2. Shape and size of the dosage form
3. Food intake and its nature:
 Viscosity
 Volume of food
 Caloric value
 Frequency of feeding
4. Effect of gender ,posture and age
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8. Gastrointestinal dynamics
 Gastric emptying occurs in both the fasting and fed states
 During the fasting state an inter-digestive series of electrical events take place which
cycle both through stomach and intestine every 2-3 hrs , which is called as inter digestive
myo-electric cycle or migrating myoelectric cycle (MMC).
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9. .
• It involves incorporation of a
drug into the dosage form.
• Ex- Anti-muscarinics
(propantheline)
• Natural materials or fat
derivatives are used such as
triethanolamine myristate ,
which stimulate the
duodenal or jejunal
receptors to slow gastric
emptying .
• First two approaches are
not used due to toxicity
problems.
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10. 10

11. High density system
 These have density greater than that of gastric fluids (1.4 g/cc).
 Above 1.6g/cc is preferable, tend to withstand peristaltic
movements of stomach.
 These formulations are prepared by coating drug on a heavy
core or mixed with heavy inert material such as iron powder,
zinc oxide, titanium dioxide, barium sulphate.
 DRAWBACK:-they are technically difficult to manufacture with a
large amount of drug because the dry material of which it is
made interacts within the gastric fluid to release its drug
contents.
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12. Floating System
 These are low density systems.
 Float over gastric contents for prolonged periods of time and
provide continuous release of the drug.
 It must maintain specific gravity lower than gastric contents
(1.004 – 1.01 gm/cm3).
 Floating dosage forms being commercialized and marketed
world-wide.
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13. Classification of floating system 13

14. Effervescent systems
1. GAS GENERATING SYSTEM
 Includes use of gas generating agents, carbonates and other organic acid
present in the formulation to produce carbon dioxide gas.
 CO2 gets entrapped in the jellified hydrocolloid layer of the systems thus
decreasing its specific gravity and making it to float over gastric content.
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15. 2.Volatile liquid/vacuum systems
 The GRT of a drug delivery system can be sustained by incorporating an inflatable
chamber.
 Inflatable chamber contains liquid (ether, cyclopentane) that gasifies at body temperature
to cause the inflatation of the chamber in the stomach.
 The device may also consist of a bio-erodible plug made up of PVA, Polyethylene that
gradually dissolves causing the inflatable chamber to release gas and collapse after a
predetermined time to permit the spontaneous ejection of the inflatable systems from
the stomach.
A. Inflatable Gastrointestinal Delivery Systems
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16. Cont.
B. Intragastric Floating Gastrointestinal Drug Delivery System
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17. Non-effervescent systems
 Non-effervescent floating drug delivery systems (NFDDS) are normally prepared from gel-
forming or highly swellable cellulose type hydrocolloids, polysaccharides or matrix
forming polymers.
 Intimate mixing of drug with a gel forming hydrocolloid which results in contact with gastric
fluid after oral administration and maintain a relative integrity of shape and a bulk density
less than unity within the gastric environment.
 The air trapped by the swollen polymer confers flotations to these dosage forms.
 Excipients used most commonly in these systems:
 hydroxypropyl methylcellulose (HPMC)
 Polyacrylates
 Polyvinyl acetate
 Carbopol
 Agar
 Sodium Alginate
 Polyethylene oxide
 Polycarbonates
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18. 1.Colloidal gel barrier systems
 Such systems contains drug with gel forming hydrocolloids meant to remain float on
stomach contents.
 These systems incorporate a high level of one or more gel forming highly swellable
cellulose type hydrocolloids. e.g. HPMC, NaCMC.
 The polymer is mixed with drugs and usually administered in hydrodynamically
balanced system capsule.
 On coming in contact with gastric fluids forms a viscous core.
 Density of system falls below 1gm/cm3. Then it starts floating.
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19. 2. Hollow microspheres
 Microballoons / hollow microspheres loaded with drugs are prepared by simple solvent
evaporation method.
 Commonly used polymers to develop these systems are polycarbonate, cellulose
acetate, calcium alginate, Eudragit S, agar and pectin and methoxylated pectin etc.
 These systems have capacity to float on acidic dissolution media containing surfactant
for about 12 hours invitro.
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20. Cont.
 The dichloromethane solution of the drug and an enteric acrylic
polymer was poured into an agitated solution of Poly Vinyl Alcohol (PVA)
that was thermally controlled at 40ºC.
 The gas phase is generated in the dispersed polymer droplet by the
evaporation of dichloromethane.
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21. 3. Alginate beads
 Spherical beads of approximately 2.5 mm in diameter can be prepared by
dropping a sodium alginate solution in to aqueous solutions of calcium chloride,
causing precipitation of calcium alginate.
 Sodium alginate+ Calcium chloride Calcium alginate+ NaCl
 The beads are then separated snap and frozen in liquid nitrogen, and freeze dried
at -40°C for 24 hours, leading to the formation of porous system.
 Maintain a floating force of over 12 hours.
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22. 4. Microporous membrane systems
 Based on the encapsulation of drug reservoir inside a Microporous
compartment.
 The peripheral walls of the drug reservoir compartment are completely
sealed to prevent any direct contact of the gastric mucosal surface with the
undissolved drug.
 In stomach the floatation chamber containing entrapped air causes the
delivery system to float over the gastric contents.
 Gastric fluid enters through the apertures, dissolves the drug, and carries
the dissolve drug for absorption.
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23. Mucoadhesive systems
 Involves the use of bio-adhesive polymers, which can adhere to
the epithelial surface in the stomach.
 Dosage form can stick to mucosal surface by following
mechanisms:
1. Wetting theory
2. Diffusion theory
3. Absorption theory
4. Electron therapy
 Bioadhesive polymers used are: - PAA, Chitosan, Sodium
alginate, HPMC, Sucralfate, Tragacanth, Dextrin, PEG.
 Limitation: - Bioadhesion is difficult to maintain due to rapid
turnover of mucin in GIT
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24. Swellable systems
 A dosage form in the stomach will withstand gastric transit if
it bigger than pyloric sphincter.
 These are the dosage forms, which after swallowing swells to
such an extent that their exit from the pylorus is prevented,
as a result the dosage form is retained in the stomach for a
prolonged period of time.
 On coming in contact with gastric fluid the polymer imbibes
water and swells.
 Chitosan, HPMC, sodium starch glycolate, carbopol are
used.
 Diclofenac, Ciprofloxacin, Furosemide are reported with
these systems.
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25. Advantages of GRDDS
 Improved Bioavailability, because of increased GRT and more time spent
by the dosage form at its absorption site.
 Controlled delivery of drugs.
 Minimizing mucosal irritation by releasing drugs slowly at a controlled rate.
 Treatment of gastrointestinal disorders such as gastroesophageal reflux,
providing local action.
 Ease of administration and better patient compliance.
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26. Disadvantages of GRDDS
 Unsuitable for drugs with limited acid solubility such as Phenytoin.
 Unsuitable for drugs those are unstable in acidic environment such as
Erythromycin.
 Drugs that irritates or causes gastric lesions on slow release such as
Aspirin & NSAID’s.
 Drugs that absorb selectively in colon such as Corticosteroid.
 Drugs that undergo a significant first-pass metabolism such as
Nifedipine
 Floating drug delivery systems require high fluid level in stomach to
float and work effectively.
 Not used for drugs that are degraded in acidic environment of
stomach i.e, Insulin
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27. Evaluation of GRDDS
1. Floating drug delivery systems:
Floating time
 Determined by using the USP dissolution apparatus containing 900 ml of 0.1 N
HCL maintained at 37oC.
 The time for which the dosage form floats is termed as the floating time.
Specific Gravity / Density
 Density can be determined by the displacement method using Benzene as
displacement medium
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28. .
2. Muco – Adhesion system
 Measurement of either tensile or shear strength is the most commonly
used invitro method to measure bio-adhesion strength.
 Measurement of tensile strength involves quantiting the force required to
break the adhesion bond between the test polymer and model membrane.
 The method typically uses modified balance or tensile tester.
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29. Swelling systems
Weight gain and water uptake
 Done by immersing the dosage in simulated gastric fluid at 37oC and
determining these factors at regular intervals.
 Dimensional changes can be measured in terms of increase in the tablet
diameter or thickness with time.
 Water uptake is measured in terms of %weight gain.
 Where,
WU = Water Uprtake
Wt= weight of dosage form at time t
Wo weight of dosage form initially
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30. Gastro-retentive products available in
the market
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31. Conclusion
 Gastro-retentive drug delivery offers various potential
advantages for drug with poor bioavailability due their
absorption is restricted to the upper gastrointestinal tract
(GIT) and they can be delivered efficiently thereby maximizing
their absorption and enhancing absolute bioavailability.
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32. References
1. Gastroretentive drug delivery systems 10.1517/17425247.3.2.217 © 2006
Ashley Publications ISSN 1742-5247 217 Ashley Publications www.ashley-
pub.com
2. Floating drug delivery systems to increase gastric retention of drugs: A
Review AV Mayavanshi* and SS Gajjar AR College of Pharmacy and GH
Patel Institute of Pharmacy, Vallabh Vidyanagar, Anand, Gujarat-388 120
3. Nayak Amit, Maji Ruma and Das Biswarup. Gastro-retentive drug delivery
system; Review. Asian. J. Pharm. Res. 2010, 3, 2-10.
4. Anand S. Surana & Rakhee K. Kotecha, “An overvew on various approaches to
oral controlled drug delivery system via gastroretention” IJPSRR, Vol-2, May-
June 2010. pp: 68-72
5. Gastroretentive drug delivery systems -Amit Kumar Nayak *, Ruma Maji,
Biswarup Das , Vol.3 Issue 1, January-March 2010
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33. .
6. Anand S. Surana & Rakhee K. Kotecha, “An overvew on various approaches to
oral controlled drug delivery system via gastroretention” IJPSRR, Vol-2, May- June
2010. pp: 68-72
7.Gastroretentive drug delivery system (grdds) Meenakshi Jassal1, Ujjwal
Nautiyal1*, Jyotsana Kundlas1, Devendra singh2, 1Himachal Institute of
Pharmacy, Paonta sahib, HP, India Tirupati life science, Paonta Sahib, HP,
India
8. Gastroretentive drug delivery systems Streubel†, Juergen Siepmann & Roland
Bodmeier†Roche Diagnostics GmbH, Sandhofer Strasse 116, 68305 Mannheim,
Germany
9. Doshi S.M., Tank H.M., Gastro Retention – An Innovation over Conventional
poorly Soluble Drugs : A review, International Journal of Pharmaceutical and
chemical Sciences, 2012;1(2):859-866
10. International Journal of Research in Pharmaceutical and Biomedical Sciences
ISSN: 2229-3701
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34. THANK YOU
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