To modify the GIT time is one of the main challenge in the development of oral controlled drug delivery system. Gastric emptying of pharmaceutical dosage form is highly variable and dependent on the dosage form and the fed/fasted state of the stomach. Normal gastric residence time usually ranges between 5 minutes to 2 hours.

1. by
SURYAKANT VERMA
(ROLL NO. 1219856522)
Under the Supervision of
Dr. VIKESH KUMAR SHUKLA
Assistant Director
DEPARTMENT OF PHARMACEUTICS
IIMT COLLEGE OF MEDICAL SCIENCE
GANGA NAGAR, MAWANA ROAD, MEERUT,
UTTAR PRADESH, INDIA

2. Sr .no . Topic Slide no
1. INTRODUCTION 1-7
2. AIM AND OBJECTIVE 8-9
3. FORMULATION REVIEW 10-16
4. LITERATURE REVIEW 17-18
5. PLAN OF WORK 19-21
6. EXPECTED OUTCOMES 22
7. REFERENCE 23
Content

4. To modify the GIT time is one of the main
challenge in the development of oral controlled drug
delivery system.
Gastric emptying of pharmaceutical dosage form is
highly variable and dependent on the dosage form
and the fed/fasted state of the stomach.
Normal gastric residence time usually ranges
between 5 minutes to 2 hours.
In the fasted state the electrical activity in the
stomach – the inter digestive myoelectric cycle or
migrating myoelectric complex (MMC) governs the
activity and the transit of dosage forms.

5. Sr.
No.
Phase Period (minutes)
1. Phase - I Period of Contraction (40 – 60 minutes)
2. Phase - II Period of intermittent contractions (20 – 40
minutes)
3. Phase - III Period of regular contractions at the
maximal frequency (10 – 20 minutes)
4. Phase - IV Period of transition between Phase – III and
Phase – I ( 0 – 5 minutes)
It is characterized by four Phases
Table: Four phases of inter digestive myoelectric cycle

6. Gastro-retentive systems can remain in the gastric
region for several hours and hence significantly prolong
the gastric residence time of drugs.
Prolonged gastric retention improves bioavailability,
tharapeutic efficacy, reduces drug waste and improves
solubility.
Such retention systems are important for the drugs that
are degraded in intestine or for drugs like antacids or
certain enzymes that act locally in the stomach.

7. Classification of floating drug delivery system
•Non-effervescent systems
1. Hollow microspheres / microballoons
2. Microporous compartment system
3. Alginate beads
4. Colloidal gel barrier system.
•Effervescent systems
1. Gas generating systems
(A) Hydrodynamically balanced system (HBS)
(B) Intra gastric bilayered floating tablets
2. Volatile liquid / vacuum containing systems
(A) Intragastric floating gastrointestinal drug delivery system
(B) Inflatable gastrointestinal delivery systems
(C) Intragastric osmotically controlled drug delivery system
(D) Intra gastric low density system
(E) Intragastric coated shell system
(F) Self correcting floatable drug delivery system

8. Floating microspheres are gastro retentive drug delivery systems
based on non-effervescent approach. Hollow microspheres are in
strict sense, spherical empty particles without core.
These microspheres are characteristically free flowing powders
consisting of proteins or synthetic polymers, ideally having a size less
than 200 micrometer.
Gastro-retentive floating microspheres are low-density systems that
have sufficient buoyancy to float over gastric contents and remain in
stomach for prolonged period.
As the system floats over gastric contents, the drug is released
slowly at desired rate resulting in increased gastric retention with
reduced fluctuations in plasma drug concentration.
HOLLOW MICROSPHERES (MICROBALLOONS)

9. Advantages
Superior to single unit floating dosage forms as such
microspheres releases drug uniformly and there is no risk of
dose dumping.
Avoidance of gastric irritation.
Improved receptor activation selectivity.
Minimized adverse activity at the colon
Less inter- and intra-subject variability.
Flexibility in dosage form design.
Improves patient compliance by decreasing dosing frequency.
Better therapeutic effect of short half-life drugs can be
achieved.
Gastric retention time is increased because of buoyancy.
.

10. Drug releases in controlled manner for prolonged period.
Sustained drug delivery/reduced frequency of dosing
Targeted therapy for local ailments in the upper GIT
Site-specific drug delivery to stomach can be achieved.
Enhanced absorption of drugs which solubilize only in
stomach.
Disadvantages
Drugs having irritant effect on gastric mucosa are not
suitable candidates for FDDS.
Drugs which are absorbed along the entire GIT and which
undergo first pass metabolism may not be desirable e.g.
Nifedipine.
They are not suitable candidates for drugs with stability or
solubility problem in stomach.

12. AIM FOR DEVELOPING GASTRORETENTIVE
HOLLOW MICROSPHERES (MICROBALLOONS)
The purpose of this work to design, optimization and in-
vitro evaluation of gastroretentive hollow microspheres
(microballoons). The specific aims were:
To increased contact time and thus improved bio- availability.
To administered an accurate dose and thus a better therapy.
To provide a prolonged drug release and thus a better
efficacy.
To increase gastric emptying time for drug having low
solubility.
Reproducibility of release kinetics.
To increase stability of a drug.
To extend the period of time over which the drug may be
released.

13. OBJECTIVE FOR MAKING GASTRORETENTIVE
HOLLOW MICROSPHERES (MICROBALLOONS)
In comparison with the traditional controlled released
preparation, it presents some advantages such as
Increasing contact time and thus improving
bioavailability.
Increased gastro retention time of drug.
Possibility of providing a prolong drug release and
thus a better efficacy.
Reduction of systemic side effects and thus reduced
adverse effects.
Reduction of the number of administrations and thus
better patient compliance.

15. Mechanism behind floating of microspheres
When microspheres come in contact with gastric fluid
the gel formers, polysaccharides, and polymers hydrate
to form a colloidal gel barrier that controls the rate of
fluid penetration into the device and consequent drug
release.
As the exterior surface of the dosage form dissolves,
the gel layer is maintained by the hydration of the
adjacent hydrocolloid layer.
The air trapped by the swollen polymer lowers the
density and confers buoyancy to the microspheres.

17. Method of preparation of floating microspheres
1. Solvent evaporation technique
(a). Oil in water emulsion solvent evaporation technique
(b). Oil in oil emulsification solvent evaporation technique
2. Emulsion solvent diffusion method
Polymers used for formulating floating microspheres
Cellulose acetate, chitosan, eudragit, acrycoat, methocil,
polyacrylates, polyvinyl acetate, carbopol, agar, polyethylene
oxide, polycarbonates, acrylic resins, etc.

18. 1. Solvent evaporation technique
Involves the emulsification of an organic solvent
(usually methylene chloride) containing dissolved
polymer and dissolved/dispersed drug in an excess
amount of aqueous continuous phase, with the aid of an
agitator.
The concentration of the emulsifier present in the
aqueous phase affects the particle size and shape.
Subsequent evaporation of the dispersed phase solvent
yields solid polymeric micro particles entrapping the
drug.
The solid micro particles are recovered from the
suspension by filtration, centrifugation, or lyophilisation.

20. 2. Emulsion solvent diffusion method
In this method solution of polymer and drug in ethanol
methylene chloride is poured into an agitated aqueous
solution of poly (vinyl alcohol).
The ethanol rapidly partitions into the external aqueous
phase and the polymer precipitates around methylene
chloride droplets.
The subsequent evaporation of the entrapped methylene
chloride leads to the formation of internal cavities within
the micro particles.
Factors to be considered during formulation
1. Addition of polymer solution
2. Effect of rotation speed
3. Effect of temperature

21. Characterization of floating microspheres
1. Percentage yield
2. Particle size
3. Bulk density
4. Tapped density
5. Carr’s (compressibility) index
6. Hausner’s ratio
7. Angle of repose
8. Drug entrapment efficiency
9. Scanning electron microscopy
10. Swelling studies
11. In vitro buoyancy
12. X-Ray diffraction technique (XRD) and differential
scanning colorimetry (DSC)
13. In-Vitro release studies
14. In-Vivo studies

22. Gastro retentive floating microspheres are very
effective in the reduction of major adverse effect of
gastric irritation.
Floating microspheres are very effective approach in
delivery of drugs that have poor bioavailability
because of their limited absorption in the upper GIT.
The higher dose of drugs can be reduced due to
increase in gastric retention time which led to low
dose frequency.
These system can remain in the stomach for long
periods and hence can release the drug over a
prolonged period of time.
These systems have bulk density of <1, as a result of
which they can float on the gastric contents.
Applications

24. 1.OBJECT- Formulation and in vitro characterization of cefpodoxime proxetil
gastroretentive microballoons
DRUG-cefpodoxime proxetil
POLYMER- Hydroxypropyl methyl cellulose, Ethyl cellulose and Tween 80
CONCLUSION- The microballoons so prepared will remain buoyant proxetil in
sustained fashion. Inferences drawn from in vitro studies suggest that
microballoons may prove as potential delivery system for cefpodoxime proxetil
by improving bioavailability in comparison to conventional dosage forms.
REFERENCE- Sharma AK,et al (2011)
2.OBJECT- Dual Templating Synthesis of Mesoporous Titanium Nitride
Microspheres
DRUG- Titanium Nitride
POLYMER- Ethyl cellulose
CONCLUSION- The synthesis of new porous materials remains an exciting area
of research, in part because of their potential use in diverse applications. Materials
having hierarchically porous nanostructures (such as bimodal mesoporous, meso–
macroporous, or mesoporous–hollow materials) are particularly intriguing
because they can uncouple overall mass transport from the chemical and physical
properties of the finer pore structure.
REFERENCE- Jin Ho Bang et al (2011)

25. 3.OBJECT- Hollow Microsphere: A Review Drug
DRUG- Ampicillin
POLYMER- Ethyl cellulose
CONCLUSION- Drug absorption in the gastrointestinal tract is a highly variable
procedure and prolonging gastric retention of the dosage form extends the time for drug
absorption. Hollow microsphere promises to be a potential approach for gastric retention.
Although there are number of difficulties to be worked out to achieve prolonged gastric
retention, a large number of companies are focusing toward commercializing this
technique.
REFERENCE- S. B. Gholap et al (2011)
4.OBJECT- Development and evaluation of aceclofenac loaded ethyl cellulose
microspheres
DRUG- aceclofenac
POLYMER- Ethyl cellulose, sodium carboxy methyl cellulose.
CONCLUSION- Solvent evaporation technique has been successfully employed to
produce aceclofenac loaded ethyl cellulose microspheres with optimal drug encapsulation
that sustained the drug release over a period of 12 h. The formulation variable drug-
polymer ratio exerted a significant influence on the drug encapsulation. The present study
signifies the utility of microspheres in retarding the drug release. This may in turn reduce
the frequency of dosing, there by improving the patient compliance.
REFERENCE- Deveswaran Rajamanickam et al (2011)

27. STAGE 1)
REVIEW OF LITERATURE
•Survey
•Review of articles
•Review of old Resources
STAGE 2)
PREFORMULATION STUDIES
•Solubility Profile of drug
•Melting Point of the drug
•Preparation of Standard Caliberation curve
•Drug Excipient Compatibility Studies
STAGE 3)
FORMULATION AND OPTIMIZATION METHODS
•Solvent evaporation technique
•Emulsion solvent diffusion method

28. STAGE 4)
PHYSICAL PROPERTIES
•Surface pH determination
•Drug content uniformity
•Particle size
•Chemical and physical stability
•Buoyancy study.
STAGE 5)
CHARACTERISATION
•Scanning Electronic Microscopy
•Particle size analysis
•FTIR study
•Drug content analysis
•Dissolution study
•Percentage yield
•Drug entrapment.

29. EVALUATION OF GASTRORETENTIVE
HOLLOW MICROSPHERES (MICROBALLOONS)
Weight variation test
Surface pH determination
Drug content uniformity
Mechanical strength.
Swelling index.

31. Floating microspheres has emerged as an efficient
approach for enhancing the bioavailability and controlled
delivery of various therapeutic agents.
Floating microspheres as gastro retentive dosage forms
precisely control the release rate of target drug to a specific
site and facilitate an enormous impact on health care.
These systems also provide tremendous opportunities in
the designing of new controlled and delayed release oral
formulations, thus extending the frontier of futuristic
pharmaceutical development.
Increased sophistication of this system will ensure the
successful advancements in the avenue of gastro retentive
microspheres therapy so as to optimize the delivery of
molecules in a more efficient manner.

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