evaluation of gastro retentive drug delivery system (GRDDS)

parametrs for evaluation of GRDDS. magnetically controlled GRDDS and also ion exchange resins systems

1. By:
Imranpasha
1st M.Pharm
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2. •Introduction to GRDDS
•Classification of GRDDS
•Magnetic systems
•Ion exchange resin system
•Evaluation of GRDDS
•Evaluation of powder blend
•Evaluation of tablets
•References
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3. •Gastro retentive drug deliveryis an approach to
prolonggastricresidence time, thereby targeting site-
specific drug releasein the upper gastrointestinal tract
(GIT) for local or systemic effects.
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4. •Poor absorption of many drugs in the lower
gastrointestinal (GI) tract necessitates controlled release
dosage forms to be maintained in the upper GI tract,
particularly the stomach and upper small intestine.
•prolonged gastric residence time (GRT) of dosage forms
in the stomach up to several hours,
•increased therapeutic efficacy of drugs by improving
drug absorption,
•suitability for targeted delivery in the stomach,
•GRDDS can enhance the controlled delivery of drugs by
continuously releasing the drug for an extended period at
the desired rate and to the desired absorption site until
the drug is completely released from the dosage form.
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5. •GRDDS are feasible for drugs that have low absorption in
the lower part of the GIT, are unstable and poorly soluble
at alkaline pH, have a short half‐life, and show local
activity at the upper part of the intestine for eradication of
Helicobacter pylori.
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In magnetic systems, a dosage form consists of active
pharmaceutical ingredient, excipients and also a small amount of
internal magnet.
An extracorporeal magnet is placed over the stomach to control
the position of the dosage form containing internal magnet.
The position and the magnetic field intensity of the
extracorporeal magnet can affect the GRT(gastroretentiontime)
Previous studies have reported that the GRT and bioavailability are
improved by magnetic tablets.

10. •Groning et al. performed a study in human volunteers
using magnetic acyclovir tablets with and without an
external magnetic field. The authors observed that the
GRT and plasma drug concentration were increased in
the presence of an extracorporeal magnet.
•Ito et al. formulated bio-adhesive granules containing
ultra‐fine ferrite and performed in vivo experiment in
rabbits. They found that an external magnetic field
intensity of 1700 G retained all granules in the stomach
for more than 2 h. However, specific positioning of the
magnet might be difficult and results in low patient
compliance.
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13. •The ion‐exchange resin system consists of the water
insoluble cross‐linked polymer (resin) that can be either
cationic or anionic. The suitable resins can be chosen
according to the drug properties.
•In case of GRDDS, drugs should be released in the
stomach and hence this system is applicable to cationic
drugs. Therefore, cationic resin can be selected.
•. The release rate of the drug from resins depends on
inherent properties of the resins such as the particle size,
cross‐linking density, type of ionogenic group.
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A specific amount of resin is poured on
a known drug concentration and mixed
homogeneously for a certain period.
The drug ions from the solution get adsorbed
onto the resin matrix and displace cations from
the resin. Such loaded drug resin complexes
are called resinates
When the resinatescome into contact with the
hydrogen ions in the acidic environment of the
stomach, hydrogen ions are exchanged with
the drug ions present in the resinatesmatrix.
As a consequence, the drug ions are released
into the gastric fluid while the resin particles
are eliminated through the large intestine.

15. •. When an ion exchange resin is highly cross‐linked, the
drug loading efficiency gets decreased
•The degree of drug resin complexation can be calculated
by dry weight resin capacity measurement methods.
•It is determined by weighing a dry resin, rewetting it in
drug solution, and displacing completely from the resin.
•The displaced ions can be assayed giving the degree of
drug resin complexation.
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Evaluation of GRDDS
Invitroassessment
Evaluation of
powder blend
Evaluation
tablets
Invivoassessment
endoscopy,
gamma
scintigraphy, X-
ray technique

18. Angle of Repose
Bulk Density
Percentage porosity
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19. measurement of tablet tensile strength,
weight variation,
friability,
drug content,
content uniformity,
in vitro drug release
Buoyancy capabilities
In vitro floating and dissolution behaviour
Particle size analysis, surface characterization (for
floating microspheres and beads)
X-Ray/Gamma Scintigraphy
Pharmacokinetic studies
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20. •Angle of repose
Angle of repose is defined as “the maximum angle
possible between the surface of the pile of powder and
the horizontal plane.” Lower the angle of repose, better
the flow properties. The angle of repose may be
calculated by measuring the height (h) of the pile and
the radius of the base(r) with ruler. Tan θ = h/r
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21. •Bulk density denotes the total density of the material. It
includes the true volume of interparticle spaces and
intraparticle pores. The packing of particles is mainly
responsible for bulk .Bulk density is defined as:
•Bulk density = Weight of the powder / Bulk volume of
powder...2
•When particles are packed, it is possible that a large
amount of gaps may be present between the particles.
Therefore, tapping of powder allows the particles to shift
and remove the voids to minimum volume. The volume
occupied by the powder in this condition represents the
bulk volume. Substituting this volume for a given weight
of powder in equation (2) gives the bulk density.
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22. •Whether the powder is porous or nonporous, the
total porosity expression for the calculation
remains the same. Porosity provides information
about hardness, disintegration, total porosity etc.
% porosity, €= void volume x100 Bulk volume %
porosity, €= (bulk volumetrue volume) x100 True
density
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25. •EXAMPLE: Propranolol Hydrochloride Floating
Tablets(200mg) evaluation.
•Formula:
•l
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SlnoIngredients Amount
1. Propranolol hydrochloride 40mg
2. HPMC E 15 LV 80mg
3. NaHCO3 20mg
4. Mannitol 58mg
5. Magnesium stearate 2mg

26. •Buoyancy lag time/lag time for floating of tablets
•Buoyancy lag time test was performed to check the
floating behavior. The tablets were dropped in the
dissolution medium, i.e., 0.1N HCl and the time taken
by them to come to the surface of the dissolution
medium, i.e., time taken for floating on surface was
reported.
•Matrix integrity
•The swollen mass of the tablets remained intact or not
was checked. Matrix integrity was observed
throughoutin vitrodissolution studies.
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27. •Swelling index
•Weight Gain and Water Uptake
•The swelling behavior of dosage units can be measured
either by studying its dimensional changes, weight gain,
or water uptake. The study is done by immersing the
tablets in 0.1N HCl at 37°C and determining these
factors at regular interval.
•Water uptake (WU) is measured in terms of percent
weight gain as given by equation below,
•where,W
t = final weight of the tablet at
timetandW
0 = initial weight of the tablet.
•Tablets were removed at intervals of 2, 4, 6, and 8h,
excess water was blotted, and tablets were weighed.
Water uptake is measured in terms of percent weight
gain. 27

28. •Thein vitrodrug release was studied by conducting
dissolution test for tablets. Dissolution was carried out
using USP XIII dissolution apparatus type II (paddle
type).
•Nine hundred milliliters of 0.1N HCl, which was
maintained at 37°C, was used as dissolution medium.
The speed of paddle was maintained at 100rpm. Five
milliliters samples were withdrawn at the time intervals of
0.5, 1, 2, 3, 4, 5, 6, 7, and 8 and up to 18h and replaced
with equal volume of fresh dissolution medium
maintained at same temperature. The samples were
filtered and suitably diluted.
•Absorbances of these solutions were recorded at
wavelength 290nm using UV spectrophotometer. All the
studies were carried out in triplicate.
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29. •To confirm the spatial and temporary placement of
floating drug delivery system, a variety of techniques
have been used like string technique, endoscopy, gamma
scintigraphy. Of these techniques, X-ray technique was
used to determine the gastric residence time of the
tablets.
•Forin vivotesting, healthy volunteers were selected.
Volunteer was asked to swallow the tablet with sufficient
water after meal in the afternoon under the supervision of
registered doctor. This was noted as zero time reading.
The successive images were then recorded at regular
intervals over a period of 4–5h. The X-ray of the tablet in
the volunteers was recorded at intervals of 0.5, 1, and
4h.
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30. •All the ingredients used in this study are transparent to X-
ray, and therefore, to make the tablets X-ray opaque, the
incorporation of BaSO
4was necessary.
•Barium sulfate has a high relative density (4.4777g/cm
2
)
and poor floating properties.
•Forin vivotests, tablets with the following composition
was compressed: 12% drug, 12% barium sulfate, HPMC
K4 M 55.05%, HPC 1.48%, NaHCO
38.92%, mannitol
3.57%, microcrystalline cellulose 7.44%, and magnesium
stearate (1%). Hardness was adjusted to 4.2kg/cm
2
.
•X-Ray/Gamma Scintigraphyis a very popular evaluation
parameter for floating dosage form nowadays. It helps to
locate dosage form in the gastrointestinal tract, by which
one can predict and correlate the gastric emptying time
and the passage of dosage form in the GIT
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33. •Pharmacokinetic studies are an integral part of the in vivo
studies and several works have been reported on these.
•Sawicki studied the pharmacokinetics of verapamil, from
the floating pellets containing drug, filled into a capsule,
and compared with the conventional verapamil tablets of
similar dose (40 mg).
•The tmax and AUC (0-infinity) values (3.75 h and
364.65ng/ml /1h respectively) for floating pellets were
comparatively higher than those obtained for the
conventional verapamil tablets. (tmax value 1.21 h, and
AUC value 224.22 mg/ml/1h)
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34. •Current State and Future Perspectives on
Gastroretentive Drug Delivery Systems Julu Tripathi †,
Prakash Thapa †, Ravi Maharjan and Seong Hoon Jeong
*
•Gastro retentive Drug Delivery System: A Review
Shivram Shinde*, Imran Tadwee, Sadhana Shahi
•Formulation and Evaluation of Gastroretentive Drug
Delivery System of Propranolol Hydrochloride Swati C.
Jagdale,Amit J. Agavekar,Sudhir V. Pandya,Bhanudas
S. Kuchekar,andAniruddha R. Chabukswar
•GASTRORETENTIVE DRUG DELIVERY SYSTEM: AN
APPROACH TO ENHANCE GASTRIC RETENTION
FOR PROLONGED DRUG RELEASE Ankur Raj
Sharma* and Afroz Khan.
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