review on gastroretentive drug delivery systems

1. Gastroretentive Drug
Delivery System
Submitted to :
Dr.Shojaei
Presented by:
Maedeh.Haedi
Collage of pharmacy
Islamic Azad University, Damghan

2. Gastroretentive Drug Delivery System :
GRDDs are an approach to prolong gastric residence time, there by
targeting site-specific drug release in the upper GIT for local or
systemic effect.
Gastro retentive dosage forms (GRDFs) are being used from a very
long time to improve therapy with several important drugs.

3. Stomach Physiology
Success of GRDDS relies on the
understanding of stomach
physiology and related gastric
emptying process.
Structurally the human stomach is
composed of three anatomical
regions:
fundus, body and antrum (pylorus)
as depicted. After a meal, the
average volume of a stomach is
about 1.5 l which varies from 250
to 500 ml during the inter-digestive
phases .
Shape: Current State and Future Perspectives on Gastroretentive Drug Delivery Systems

4. The part made of the fundus and the body acts as a reservoir of any
undigested material, while the antrum performs as the principal site for the
mixing action. Being the lower part, the antrum works as a pump for gastric
emptying by a propelling action.
Pylorus acts to separate the stomach from the duodenum and plays a major
role in gastric residence time of the ingested materials.
However, the pattern of the gastric motility is different for the fasting and fed
state.The gastric motility pattern is systematized in cycles of activity as well as
quiescence. The duration of each cycle is 90-120 min and it contains four
phases .
The motility pattern of the stomach is usually called migrating motor complex
(MMC).

5. Four phases of The motility pattern :
Phase 1 A prolonged period of quiescence (40-60% of
total time);
30–60 min
Phase 2 Increased frequency of action potentials and
smooth muscle contractility (20-30% of total
time);
20–40 min
Phase 3 A few minutes of peak electrical and
mechanical activity .
10–20 min
Phase 4 Declining activity which merges with the next
Phase I
0–5 min

6. Criteria for selection of drug candidate for GRDDS
The gastro retentive drug delivery systems are suitable for following types of
drug therapy:
1. Drugs those are locally active in the stomach e.g misoprostol,
antiacids .
2. Drugs that have narrow absorption window in gastrointestinal tract
(GIT) for example, LDOPA, paraaminobenzoic acid, furosemide,
riboflavin etc.
3. Drugs that are unstable in the intestinal or colonic environment e.g.
captopril, ranitidine HCl, metronidazole.
4. Drugs that disturb normal colonic microbes e.g. antibiotics against
Helicobacter pylori.
5. Drugs that exhibit low solubility at high pH values e.g. diazepam,
chlordiazepoxide, verapamil HCl .

7. Bioavailability
challenge
Drug Therapeutic indications
Local activity ‫رانیتیدین،لووفلوکساسی‬‫ن‬ Peptic ulcer,reflux
esophagitis,eradication of
H.pylory
Plasma fluctuations ‫کالریترومایسین‬ UTI,respiratory & GI infection
Unstable at alkaline
pH
‫وراپامیل،کاپتوپریل‬ Hypertension
Low solubility at
alkaline pH
‫افلوکساسین‬
‫سیناریزین‬
UTI,respiratory & GI infection
Nausea,vretigo,motion sickness
Narrow absorption
window
‫ریبوفالوین‬
‫سیلوستازول‬
‫پرگابالین‬
Mouth ulcer , Inhibits platelet
aggregation
Fibromyalgia,neuropathy
Short halfe-life,
Narrow absorption
window
‫لوودوپا‬
‫متفورمین‬
Parkinson
Type II diabetes
Poor absorption from
lower GIT
‫اتنولول‬
‫الفوتیدین‬
Hypertension
Gasteric/duodenal ulcer

9. Shape:Gastroretentive Dosage Forms for Prolonging Gastric Residence Time/ doi.org/10.2165/00124363-
200721020-00005

10. Advantages of GRDDS :
1. Enhanced bio-availability.
2. Reduced frequency of dosing.
3. Targeted therapy for local ailments in the upper GIT.
4. Patient compliance.
5. Improved therapeutic efficacy.

11. Disadvantages of GRDDS
1. Requirement of high levels of fluids in stomach for the delivery system
to float and work efficiently.
2. Requires the presence of food to delay gastric emptying.
3. Drugs, which undergo significant first pass metabolism, may not be
desirable candidates for this drug delivery system since the slow gastric
emptying.
4. May lead to alter systemic bioavailability.
5. Drugs having solubility or stability problems in the highly acidic
gastric environment or which are irritants to gastric mucosa cannot be
formulated as GRDDS.

12. Category GRDD systems:
Gastroretentive Drug Delivery System (GRDDS) can elevate the
controlled delivery of drugs that have an absorption window by
continuously releasing the drug for a constant period of time before it
extends its absorption site. Includes :
A- floating system,
B- dilation and expanding system,
C- muco - adhesive system,
D- high density system
E-Magnetic systems
F-Ion-exchange resin systems

13. There are various factors that affect the performance of
gastroretentive dosage forms.
These factors are mainly categorized into :
- pharmaceutical factors,
- physiological factors,
- patient-related factors.

14. Pharmaceutical factors :
For the successful design of GRDDS, it is important to understand the role
of excipients and polymers on various types of GRDDS.
For instance, in the mucoadhesive system, polymers with high muco
adhesion strength, such as carbopol and hydroxypropyl methylcellulose
(HPMC)
Likewise, with the expandable system, polymers with high swelling
properties are more desirable.
the molecular weight, viscosity, and physiochemical properties of polymers
can also affect the dosage form.
Moreover, the shape and size of the dosage unit is also important in
floating systems . Similarly, the density of the dosage form is also an
important factor for low- and high-density systems

15. Polymers commonly used to formulate GRDDS:
1. Sodium alginate :
Alginates are biodegradable hydrophilic polymers consisting of β-D-
mannuronic acid & α-L-glucuronic acid residues joined by 1, 4-glycosidic
linkages .
These polysaccharides found in brown seaweed such as Laminaria
Hyperborea.
Several alginate salts are available as sodium alginate, calcium alginate,
ammonium alginate, and potassium alginate. Specially; sodium alginate
has been commonly used in the formulation of GRDDS

16. Alginates can be chosen in such formulations as it exhibits good
characters as biocompatibility, biodegradable, nontoxic in addition to
it experience mucoadhesive properties .These polymers form a
viscous gel layer upon contact with gastric fluids to form low-density
dosage form. Alginate can form cross-linking with polyvalent cations
which result in the formation of stable gellike matrices .
Example:Sodium alginate has been used as a polymer in the preparation
of gastroretentive drug delivery tablet of domperidone .
2. Carbopol :It is pH dependent polymer used in the preparation of
GRDDS due to its ability to swell upon contact with gastric fluid forming
low-density dosage form which can prolong the gastric residence time.
HPMC is commonly used with carbopol in order to impart its viscosity

17. 3. Hydroxy propyl methyl cellulose (HPMC)
It is a water-soluble polymer, available in a wide range of molecular
weights and viscosity grades. In addition, it has a unique swelling/erosion
characteristics which reflect its ability to control drug release .
HPMC K4M has been used as a polymer in the preparation of
gastroretentive floating tablet of ibuprofen, and the tablet remains float for
more than 13 h.
4. Polymethacrylate (Eudragits®)
Eudragits are commonly used in controlled release DDS as release
retardant .They are classified into polycations as Eudragit E, Eudragit RS,
and Eudragit RL; while Eudragit L, and Eudragit S are polyanions

18. Floating systems:
Floating systems are low-density systems that have sufficient
buoyancy to float over the gastric contents and remain in the stomach for a
prolonged period.
While the system floats over the gastric contents, the drug is released
slowly at the desired rate which results in increased GRT and reduces
fluctuation in plasma drug concentration.
Floating systems can also be classified as effervescent and
noneffervescent systems.

19. Shape :Gastro-retentive oral drug delivery systems: a promising approach for narrow absorption window drug/
Journal of Advanced Biomedical and Pharmaceutical Science/page 104
Raft‐forming systems

20. The effervescent systems :
The effervescent systems are matrix type system .
These systems are classified according to the mechanism of
floating into:
- Gas generating systems
- Volatile liquid systems

21. Gas generating systems :
The mechanism of floating of these systems depends on the production
of carbon dioxide due to the reaction between carbonate or bicarbonate
incorporated in the formulation and the gastric acid or co-formulated
acids as citric or tartaric acid, and the gas retained in the gel
hydrocolloid matrix due to the incorporated polymer as methyl
cellulose, chitosan and Carbomer .
Example:Floating multi-layer tablet of anhydrous theophylline has
been prepared using sodium bicarbonate as a gas generating agent; in
vitro studies revealed that the optimized formulations were able to float
over the gastric content for 8 h with sustained release properties, but
unfortunately, there was no data about the bioavailability of theophylline.

22. Shape : Effervescent Floating Drug Delivery System: A Review /Pramod Kumar Sharma/ Published 2014

23. Volatile liquid systems
The system contains an inflatable chamber , which contains a volatile
liquid (as Ether or cyclopentane), which volatilizes at body temperature
allowing the system to increase in size and float over the gastric fluids .

24. Noneffervescent systems:
The floating of non-effervescent systems relies on two possible
mechanisms:
The first one; depends on the incorporation of high swelling and gelling
capacity polymer as cellulose type hydrocolloid.
Upon coming into contact with gastric fluid, these gel formers,
polysaccharides and polymers hydrate and form a colloidal gel barrier.
The second mechanism may be related to floating of such systems depend
on incorporating a gas-filled chamber of specific gravity into a microporous
component that allows the system to float
- Hydrodynamically balanced gel systems
- Microporous compartment systems
- Alginate beads -Microballoons/ hollow microspheres
- Raft‐Forming Systems:

25. A. Hydrodynamically balanced gel systems
Formulation of hydrodynamically balanced systems depends on
1)gel-forming hydrocolloid together with the drug that allows
the drug to remain buoyant over the gastric fluids.
These systems may contain one or more gel-forming cellulose
type hydrocolloid as; alginic acid.
It also contains 2) matrix forming polymers as Polycarbophil,.
Hydrodynamically balanced system of metformin has been
prepared like a single unit floating capsule using various polymers
as HPMC K4M and ethyl cellulose.

26. Hydrodynamically balanced systems:

27. B. Microporous compartment systems
In these systems, the drug is encapsulated into microporous
compartment having pores along its top and bottom surface, this
chamber containing entrapped air which causes the system to float.
Gastric fluid can pass through the pores and dissolve the drug
which can be released through the pores .Controlled porosity
osmotic pump tablets for salvianolic acid (SA) have been prepared
using an artificial network method, in vitro release studies showed
sustain drug release for 12 h .
Shape:FORMULATION AND EVALUATION OF GASTRO RETENTIVE FLOATING MICROSPHERES OF FELODIPINE/Radhika
Parasuram Rajam, Praveen, +2 authors Radhika Parasuram/Published 2015

28. C. Alginate beads
In this approach, a solution of sodium alginate is dropped into an aqueous
solution of calcium chloride and caused the precipitation of calcium
alginate. These beads are then separated and air dried or freeze-dried.
Shape:Calcium alginate hydrogel beads with high stiffness and extended dissolution behaviour / European Polymer Journal/
Volume 75, February 2016, Pages 343-353

29. Sodium alginate solution was prepared in distilled water at a
concentration of 2% (w/v).
CaCl2 and BaCl2 were also prepared by 10% w/v and diluted to 1% w/v.
A disposable Terumo® syringe (3 mL) was filled with homogenized
alginate solution, which was subsequently extruded using a KDS230
syringe pump .
Alginate dispersion was then added dropwise into the cuvettes filled
with 3 mL of Ca2+ solution and Ba2+ solution at a constant injection rate,
enabling calcium and barium ion-crosslinked alginate and the gelled
beads to be created uniformly . The experiment was controlled around the
set room temperature (25°C) and low temperature (8°C) and repeated at
least three times.

30. Shape:The Size Stability of Alginate Beads by Different Ionic Crosslinkers /Volume 2017 |Article ID 9304592

31. Calcium alginate–Egg-box structure :
Alginate is composed of (1→4)-β-D-mannuronic acid (M) and a-L-guluronic
acid (G) units in the form of a homopolymeric (MM- or GG-blocks) and
heteropolymeric sequences (MG- or GM-blocks)
If two G-block regions are aligned side by side, a diamond shaped hole
results. This hole has
dimensions that are ideal for
the cooperative binding of
calcium ions.
Shape: Preparation of Porous Calcium Alginate Beads and Their Use for Adsorption of O-Nitrophenol from Aqueous Solutions

32. Drug loading was carried out by two methods, designated as the sequential
method and the simultaneous method.
In the sequential method, calcium alginate beads were prepared as
described in the previous .
The wet beads were then immersed and stirred for 1hr in a solution
containing TMZ (concentration ranging from 2-3 % w/v),filtered and washed
with distilled water. TMZ-loaded calcium alginate beads were obtained by
subsequent drying.

33. In the simultaneous method, the gelation of beads by calcium ions
occurred simultaneously with the drug loading into the beads.
The sodium alginate solution was introduced dropwise into CaCl2 solutions
(concentration ranging from 1-3%w/v) which also contained TMZ
(concentration ranging from 2-3% w/v).
After 1hr of interaction, the beads were removed from the counter ion
solution. The drug loaded beads were washed and dried in a manner similar
to that of blank beads (beads without drug).

34. This results in a porous system which can float over the gastric content .
These beads can prolong the GRT for more than 5.5 h .
- Combination of famotidine and quercetin for the treatment of peptic
ulcer

35. D. Microballoons/ hollow microspheres
The technique used in the preparation of these systems includes
solvent evaporation or solvent diffusion methods which create
hollow inner core .
Polymers such as polycarbonate, chitosan are commonly used in
the preparation of such systems .
The amount of drug released can be controlled by optimizing the
polymer quantity and the polymer plasticizer ratio.
Riboflavin as hollow microspheres = to prolong the GRT and
improve its bioavailability .
Hollow microspheres of theophylline = could remain float for more
than 24 h

36. Most of the floating drug delivery systems are dominated by single
unit systems. They are having cons of high variability of the GI
transit time, due to its “All or nothing” emptying process.
To overcome this issue, multiple unit floating systems can be
designed which can be widely distributed in GI tract upon
administration and provide more reliable and long-lasting drug delivery
to stomach.
Hollow microspheres can be prepared by following techniques:
-Solvent evaporation technique
-Emulsion solvent diffusion technique
-Spray drying method

37. Solvent evaporation technique
There are different methods to use microencapsulation by solvent
evaporation technique. The choice of the method that will give rise to an
efficient drug encapsulation depends on the hydrophilicity or the
hydrophobicity of drug.
For insoluble or poorly water-soluble drugs, the oil-in-water (o/w) method
is frequently used. This method is the simplest and the other methods derive
from this one. It consists of four major steps :
(1) Dissolution of the hydrophobic drug in an organic solvent containing the
polymer;
(2) Emulsification of this organic phase (dispersed phase) in an aqueous
phase (continuous phase);
(3) After formation of stable emulsion, evaporation of the solvent from the
dispersed phase by increasing temperature or under continuous stirring

38. At room temperature, transforming droplets of dispersed phase into solid
particles; and
(4) Recovery and drying of microspheres to eliminate the residual solvent
Schematic presentation of microspheres preparation by solvent
evaporation techniqu :
Shape:GASTRORETENTIVE DRUG DELIVERY SYSTEMS: FROM CONCEPTION TO COMMERCIAL SUCCESS /J Crit Rev, Vol 4, I
ssue 2, 10-21Review Article

39. Schematic presentation of microballoon preparation by emulsion
solvent diffusion technique:
Shape:GASTRORETENTIVE DRUG DELIVERY SYSTEMS: FROM CONCEPTION TO COMMERCIAL SUCCESS /J Crit Rev, Vol 4, I
ssue 2, 10-21Review Article

40. Raft‐Forming Systems:
Raft‐forming systems are another type of GRDDS, formulated with
effervescent excipients and gel forming polymers in order to achieve the
sustained drug delivery. illustrates the concept of these systems, which mainly
focuses on achieving localized effects because floating rafts act as
blockades between esophagus and stomach. Thus, they can be used for the
effective management of gastric esophageal reflux disease.
When raft‐forming systems come into contact with gastric fluid, they swell and
form a viscous cohesive gel leading to the formation of a continuous layer
termed as rafts .
Example: used sodium alginate as a gel‐forming polymer, and sodium
bicarbonate and acid neutralizer as gas‐ generating agents. Thus, CO2 gas
is generated that lowers the bulk density of the system, and as a result, the raft
floats on the gastric fluid.

41. developed a controlled release floating raft system of mebeverine
hydrochloride, and evaluated different excipients for their floating behavior and
in vitro controlled‐release. It forms a viscous and cohesive gel when it swells
and entraps CO2 bubbles produced by the reaction of carbonates and gastric
fluid .
The formed raft can remain intact in the stomach for several hours, promoting
the sustained release of the drug. Such rafts are particularly useful for
delivering antacid drugs such as aluminum hydroxide, calcium carbonate, and
simethicone .However, the mechanical strength of the systems is weak and
can be easily disrupted by the MMC.

42. Shape:Current State and Future Perspectives on Gastroretentive Drug Delivery Systems

43. Muco-adhesive systems
Muco-adhesive systems are those which bind to the gastric epithelial
cell surface or mucin and serve as a potential means of
extending gastric residence time of drug delivery system in
stomach, by increasing the intimacy and duration of contact of
drug with the biological membrane.
Binding of polymers to mucin/epithelial surface can be divided into
three broad categories;
- Hydration-mediated adhesion
- Bonding-mediated adhesion
-Rreceptor-mediated adhesion.

44. Shape:Current State and Future Perspectives on Gastroretentive Drug Delivery Systems

45. Theories Mechanisms of Mucoadhesive
wettability Bioadhesive polymers penetrate and develop intimate
contact with mucous layers
diffusion Physical entanglement of mucin strands & flexible
polymer chains.influenced by M.W, crosslinking
density,chain flexibility
adsorption Bioadhesive is due to primary forces (ionic,
covalent,metalic) and secondry forces(vander waals
,hydrophobic and hydrogenic bonds)
electronic Attractive electrostatic forces :glicopro and material

46. 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 sphincter.

47. Shape:Current State and Future Perspectives on Gastroretentive Drug Delivery Systems

48. High-Density Systems :
High-density systems have a density greater than that of gastricfluid.
Commonly used excipients of these systems include barium sulfate,
zinc oxide .
The high-density materials had slower GRTs than light-density
materials.
small high-density pellets are able to resist gastric peristaltic
movements due to their retention in the antrum folds, increasing the
gastrointestinal tract time from 5.8 to 25 h.
*Even though this system has the potential to improve the GRT, it is
difficult to design high-density pellets containing high-dose drugs.

49. Shape:Current State and Future Perspectives on Gastroretentive Drug Delivery Systems

50. Magnetic systems :
This system based on the dosage form contains a small
magnet and another magnet is placed on the abdomen over
the position of the stomach using an extracorporeal magnet,
this system can prolong the GRT .
Peroral acyclovir depot tablets with internal magnets have
been prepared to prolong the GRT of acyclovir.
An external magnet was used to prolong the gastric residence
times of the dosage forms and the duration of absorption of
acyclovir.

51. The magnetic depot tablets contained 200 mg acyclovir, the mean
area under the plasma concentration-time-curve (AUC0–24h), was
2802.7 ng/ml.h in the presence of the extracorporal magnet,
compared with 1598.8 ng/ml.h Without the extracorporal magnet as
a mean AUC0–24h.
Shape: Current State and Future Perspectives on Gastroretentive Drug Delivery Systems Article in Pharmaceutics · April 2019

52. Ion-exchange resin systems :
Drug is loaded into the resin to form the resin loaded drug complex,
which can be combined with floating delivery or bioadhesive
systems.
The ion‐exchange resin system consists of the water insoluble
cross‐linked polymer (resin) that can be either cationic or anionic. In
general, it is designed to release the drug in a controlled manner.
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. 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.

53. Such loaded drug resin complexes are called resinates.
When the resinates come into contact with the hydrogen ions in the
acidic environment of the stomach, hydrogen ions are exchanged
with the drug ions present in the resinates matrix. As a consequence,
the drug ions are released into the gastric fluid while the resin
particles are eliminated through the large intestine .
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.
When an ion exchange resin is highly cross‐linked, the drug loading
efficiency gets decreased .

54. 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. Even though this system alone may not be suitable to
increase the GRT, the ion exchange resin can be combined with floating
delivery systems or bioadhesive systems to prolong the GRT .
Some of its limitations may be difficulty in estimating the amount of
bound resin with drug, and safety issues concerning its ingestion.

55. Shape:Ion-exchange resins: carrying drug delivery forward/Vikas Anand, Raghupathi Kandarapu and Sanjay Garg/ DDT Vol. 6, No. 17 September 2001

56. Dual-mechanism gastroretentive drug delivery system:
we aimed to prepare a gastroretentive drug delivery system that would
be both highly resistant to gastric emptying via multiple mechanisms
and would also potentially induce in situ supersaturation.
The bioadhesive floating pellets, loaded with an amorphous solid
dispersion, were prepared in a single step of hot-melt extrusion
technology. Hydroxypropyl cellulose and hypromellose were used as
matrix-forming polymers, and felodipine was used as the model
drug.
The foam pellets were fabricated based on the expansion of CO2,
which was generated from sodium bicarbonate during the melt-
extrusion process

57. Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion

58. References:
1. Gastro-retentive drug delivery systems and their in vivo success/Asian
Journal of Pharmaceutical Sciences
2. Current State and Future Perspectives on Gastroretentive Drug Delivery
Systems/Julu Tripathi†, Prakash Thapa† , Ravi Maharjan and Seong Hoon
Jeon
3. Gastro-retentive oral drug delivery systems: a promising approach for
narrow absorption window drugs / J. Adv. Biomed. & Pharm. Sci. 2 (2019)
98-111
4. Gastroretentive Drug Delivery System: An Overview / International
Journal of Research in Pharmaceutical and Biomedical Sciences ISSN:
2229-3701

59. 5. Gastroretentive drug delivery systems: A review /Satinderkakar,
Ramandeep Singh / African Journal of Pharmacy and Pharmacology
6. Gastro-retentive drug delivery systems and their in vivo success: A
recent update / International Islamic University Malaysia (IIUM), Kuantan
25200, Malaysia
7. Ion-exchange resins: carrying drug delivery forward/Vikas Anand,
Raghupathi Kandarapu and Sanjay Garg/ DDT Vol. 6, No. 17 September
2001
8. Development and evaluation of calcium alginate beads prepared by
sequential and simultaneous methods / Brazilian Journal of
Pharmaceutical Sciences/ vol. 46, n. 4, out./dez., 2010
9. Preparation of Porous Calcium Alginate Beads and Their Use for
Adsorption of O-Nitrophenol from Aqueous Solutions

60. 10.The Size Stability of Alginate Beads by Different Ionic Crosslinkers
/Volume 2017 |Article ID 9304592 | 7 pages]
11. Calcium alginate hydrogel beads with high stiffness and extended
dissolution behaviour / European Polymer Journal/Volume 75,
February 2016, Pages 343-353
12. GASTRORETENTIVE DRUG DELIVERY SYSTEMS: FROM
CONCEPTION TO COMMERCIAL SUCCESS /J Crit Rev, Vol 4, Issue 2,
10-21Review Article
13. Boron WF, Boulpaep EL (2012). Medical physiology : a cellular and
molecular approach (Updated second ed.). Philadelphia, Pa.:
Saunders. ISBN 978-1-4377-1753-2.
14. PharmPK Discussion - Absorption window/PharmPK Discussion

61. List Archive Index page:
https://www.pharmpk.com/PK07/PK2007006.html#:~:text=%3EWhat%20is%
20the%20definition%20of,segments%20of%20the%20GI%20tract.
15.Gastroretentive Dosage Forms for Prolonging Gastric Residence
Time/ doi.org/10.2165/00124363-200721020-00005
16. Effervescent Floating Drug Delivery System: A Review /Pramod
Kumar Sharma/ Published 2014
17. FORMULATION AND EVALUATION OF GASTRO RETENTIVE
FLOATING MICROSPHERES OF FELODIPINE/Radhika Parasuram
Rajam, Praveen, authors Radhika Parasuram/Published 2015
18. Dual-mechanism gastroretentive drug delivery system loaded with
an amorphous solid dispersion prepared by hot-melt extrusion /
doi.org/10.1016/j.ejps.2017.02.040