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RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE
KARNATAKA
ANNEXURE – II
PROFORMA OF REGISTRATION OF SUBJECT OF DISSERTATION
1.
NAME OF THE CANDIDATE AND
ADDRESS
2.
NAME OF THE INSTITUTION
VISVESWARAPURA INSTITUTE OF
PHARMACEUTICAL SCIENCES
BANGALORE – 70
3.
COURSE OF THE STUDY AND
SUBJECT
MASTER OF PHARMACY IN
PHARMACEUTICS
4.
DATE OF ADMISSION OF THE
COURSE
27/06/2008
5.
TITLE OF THE TOPIC
VIJAY V. KATHIRIYA
#50, 1st FLOOR, 4th MAIN, 5th CROSS,
NEAR BALAJI KALYAN MANTAPA,
BSK 3rd STAGE, BANGALORE-85
FORMULATION AND EVALUATION
OF SUSTAINED RELEASE
MICROSPHERES OF ANTIDIABETIC
DRUG
6.
BRIEF RESUME OF THE PROJECT STUDY
6.1 NEED FOR THE STUDY:
 The purpose of investigation in this research work is to formulate and
evaluate sustained release microsphere of antidiabetic drug for
maintenance of glucose levels in the body for 8 to 12 hours.

Background of the invention microparticles, microspheres, and
microcapsules, referred to herein collectively as "microparticles", are
solid or semi-solid particles having a diameter of less than one
millimeter, more preferably less than 100 microns, which can be
formed of a variety of materials, including synthetic polymers,
proteins, and polysaccharides. Microparticles have been used in many
different applications, primarily separations, diagnostics, and drug
delivery. The categories of physiologically active agents which can be
used in the present invention include, but are not limited to, antibiotics,
hematopoietics, anti-infective agents, antidementia agents, antiviral
agents, antitumor agents, antipyretics, analgesics, anti-inflammatory
agents, antiulcer agents, antiallergic agents, antidepressants,
psychotropic agents, cardiotonics, antiarrythmic agents, vasodilators,
antihypertensive agents such as hypotensive diuretics, antidiabetic
agents, anticoagulants, cholesterol lowering agents, therapeutic agents
for osteoporosis, hormones, vaccines. 1

The primary benefit of a sustained release dosage form, compared to a
conventional dosage form, is the uniform drug plasma concentration
and therefore uniform therapeutic effect. Over the past two decades,
sustained release dosage forms have made significant progress in terms
of clinical efficacy and patient compliance. Matrix devices, due to their
chemical inertness, drug embedding ability and drug release character,
have gained steady popularity for sustaining the release of a drug.2

In the controlled drug delivery area, molecules are encapsulated within
microparticles or incorporated into a monolithic matrix, for
subsequent release. A number of different techniques are routinely
used to make these microparticles from synthetic polymers, natural
polymers, proteins and polysaccharides, including phase separation,
solvent evaporation, emulsification, and spray drying. Generally the
polymers form the supporting structure of these microspheres, and the
drug of interest is incorporated into the polymer structure. Exemplary
polymers used for the formation of microspheres include
homopolymers and copolymers of lactic acid and glycolic acid (PLGA)
as described in U. S.1
2
6.2 REVIEW OF LITERATURE:
1. Sustained release microspheres of chlorpromazine were prepared from
Eudragit® RS 100 by an emulsion-solvent evaporation method using a sixbaffled vessel. The morphology of microspheres was characterized by
scanning electron microscopy (SEM). In the presence of aluminium
tristearate (5%), microspheres were spherical in shape and uniform. The
release of chlorpromazine from microspheres was pH-independent. With
increasing amount of aluminium tristearate and increasing ratio of
Eudragit® RS 100/drug from 1:1 to 9:1, the particle size of chlorpromazine
microspheres was reduced and the release rate decreased. The
microspheres prepared with the polymer/drug ratio of 9:l produced a 12-h
sustained release pattern.3
2. Meclofenamic acid (MFA) sustained-release microspheres were prepared
by the solvent evaporation method using cellulose propionate (CP)
polymer and acetone as the polymer solvent. Polyethylene glycol (PEG)
was used as a channeling agent to improve the release properties of MFA
at 1:2:1 drug to polymer to PEG ratio. The microspheres prepared at
three different speeds (600, 800 and 1000 rpm) were characterized and
release profiles were carried out in phosphate buffer, pH 8.0 at 37°C.The
release rate of MFA from these microspheres was not affected by the
molecular weight of CP polymer. PEG 2000 was found to have a more
enhancing effect on the rate of the release than PEG 4000.4
3. Metoclopramide was encapsulated with poly (D, L-lactide co glycolide)
copolymers of different molecular weights using the emulsification/solvent
evaporation technique. The effect of the polymers' molecular weights as
well as the polymer-to-drug ratios on the microsphere preparation was
investigated. The release rate of the drug was studied for 96h in a
phosphate buffer of pH 7.4. Data revealed that a higher yield was obtained
with polymers of lower molecular weights. A lower yield was also obtained
with increasing the drug-to-polymer ratios. The release of the drug mainly
followed zero order kinetics. The release rate was a function of both the
polymers' molecular weights and the drug-to-polymer ratios.5
4. Ofloxacin microspheres were formulated using polyglycolic acid-co-dllactic acid (PGLA) by the emulsion solvent evaporation technique.
Ofloxacin release from the microspheres was biphasic with an initial burst
release followed by a slow release phase. An optimum slowing down of
release was observed when the phase volume was 29%. Above and below
this phase volume, release of ofloxacin was higher. The study indicates that
various rates of ofloxacin release are possible by varying formulation
conditions. This should provide a means for formulating sustained release
microspheres of antibiotics for the treatment of biofilm infections
associated with the bone.6
3
5. Ethylcellulose is used as a retardant to prepare the sustained release of
potassium chloride microspheres by drying in a liquid process. The effect
of sustained release of potassium from ethylcellulose microspheres was
evaluated by the in vitro dissolution test, and was compared to a
commercial product (Slow-K). Satisfactory results could be obtained
considering size distribution and shapes of microspheres by incorporating
aluminum stearate. Satisfactory results could be obtained considering size
distribution and shapes of microspheres by incorporating aluminum
stearate. The encapsulation efficiency and loading capacity were about
84–93 and 36%, respectively.7
6. Ketoprofen microspheres (MS) were prepared by the dry-in-oil method
using ethylcellulose (EC) as a matrix polymer. Further, the microspheres
modified by addition of polyethylene glycol (PEG) and hydroxypropyl
cellulose (HPC), called MS-P and MS-H, respectively, were prepared. The
in vitro release was examined in pH 6.8, at 37°C and 60 rpm. Chitosancoated ketoprofen microparticles (Chi-MP) were prepared by the
precipitation technique and evaluated for adhesion. The microspheres
with moderate drug content, prepared by addition of modest amount of
PEG, exhibited better gradual drug release. Chi-MP showed agood
mucoadhesion. Chi-MP tended to show the higher and steadier plasma
levels than MS.8
7. Methacrylate microparticles were prepared by Spray-drying for the
delivery of ascorbic acid via the oral route. As polymers different acrylic
compounds were considered, namely Eudragit® RL, L and RS.
Microspheres were first characterized by size and morphology by
scanning electron microscopy, then in vitro release kinetics by mean of
dialysis method were studied. These microspheres showed a good
morphology and size distribution that permit to propose them as
candidate for the delivery of vitamin C.9
8. Microparticles containing diltizem hydrochloride were prepared by the
spray-drying technique using acrylatemethacrylatecopolymers, Eudragit
RS and Eudragit RL, as coating materials. Spray-drying using
dichloromethane as the solvent resulted in microspheres whereas using
toluene gave microcapsules with the drug coated by the polymer. The
particle size distribution for both microspheres and microcapsules was
narrow. The results indicate that spray-drying is a method that can be
used to prepare microparticles from the Eudragit acrylic resins RLand RS
with a narrow particle size distribution. Drug release rate can be
controlled by choice of polymer type and production conditions during
spray-drying.10
4
9. Sustained release (SR) particles for pulmonary drug delivery using
terbutalin sulphate were prepared using spray dryer. Sustained release of
the model drug, from the microspheres was proportional to drug loading
and phospholipids content. Microspheres with a 33% drug loading
exhibited sustained release of 32.7% over 180 min in phosphate buffer. No
significant burst release was observed which suggested that nanoparticles
were coated effectively during spray-drying. The sustained release
microspheres were formulated as a carrier-free dry powder for
inhalation.11
10. Ketoprofen microspheres were prepared by a spray-drying technique
using cellulose acetate butyrate (CAB) and hydroypropylmethylcellulose
phthalate (HPMCP), in different weight ratios. Spray-dried microparticles
were characterized in terms of shape, size, and production yield and
encapsulation efficiency. Tablets were prepared by direct compression of
the microparticles mixed with maltose and, in some cases,
hydroypropylmethylcellulose (HPMC). In-vitro release studies were
performed both at acidic and neutral pHs. The microparticles give a rapid
or prolonged drug release.12
6.3 OBJECTIVES OF THE STUDY:
7.

The objective of this study was to prepare sustained release microspheres
using various polymers.

To evaluate the particle size, drug entrapment efficiency, drug
content, In-vitro release study.

In order to elucidate release kinetics it is necessary to fit drug
release data into a suitable model. The commonly adopted
models for understanding the release of drugs from matrices are
zero-order equation, first-order equation, Higuchi equation and
Korsmeyer-Peppas simple exponential equationmodels. These
simple exponential equation models have been used to elucidate
the mode of release.
MATERIALS AND METHODS
Drug: A model antidiabetic drug.
Method: Spray drying technique.
5
7.1 SOURCE OF DATA
Journals, Internet, Text books, Web resources and E journals
(European Journal of Pharmaceutics and Biopharmaceutics, Indian journal of
pharmaceutical science,) and experimental works which includes formulation
evaluation and stability studies.
7.2 METHOD OF COLLECTION OF DATA
The data related to physiochemical details of the drug will be collected
from drug information center, various standard books, journals & other sources
like research literature data bases such as science direct etc and laboratory
experiments.
7.3 DOES THE STUDY REQUIRE ANY INVESTIGATIONS OR
INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER
HUMANS OR ANIMALS? IF SO PLEASE DESCRIBE BRIEFLY
-No7.4 ETHICAL CLEARANCE:
-NA7.5 PLACE OF STUDY:
Visveswarapura Institute Of Pharmaceutical Sciences, Bangalore-70.
8.
LIST OF REFERENCES:
1. Scott TL, Brown LR, Riske FJ, Blizzard CD, Rashba-Step J. Sustained
release microspheres. 09/420,361 18.10.1999 US
2. Basak SC, Kumar KS, Ramlingam M. Design and release characteristics
of sustained release tablet containing metformin HCl. Rev Bras Cienc
Farm 2008; 44(3).
3. Gao ZG, Oh KH, Kim CK. Preparation and characterization of sustainedrelease microspheres of chlorpromazine. J Microencapsul 1998; 15(1): 7583.
4. Khidr SH, Niazy EM, El-Sayed YM. Development and In-vitro evaluation
of sustained-release meclofenamic acid microspheres. J Microencapsul
1998; 15(2): 153-63.
6
5. Elkheshen SA, Radwan MA. Sustained release microspheres of
metoclopramide using poly (D,L-lactide-co-glycolide) copolymers. J
Microencapsul 2000; 17(4): 425-35.
6. Habib M. Preparation and characterization of ofloxacin microspheres for
the eradication of bone associated bacterial biofilm. J Microencapsul 1990;
16(1): 27-37.
7. Wu PC, Huang YB, Chang JI, Tsai MJ, Tsai YH. Preparation and
evaluation of sustained release microspheres of potassium chloride
prepared with ethylcellulose. Int J Pharm 2003; 260(1): 115-21.
8. Yamada T, Onishi H, Machida Y. In-vitro and In-vivo evaluation of
sustained release chitosan-coated ketoprofen microparticles. Yakugaku
Zasshi 2001; 121(3): 239-45.
9. Esposito E, Cervellati F, Menegatti E, Nastruzzi C, Cortesi R. Spray dried
eudragit microparticles as encapsulation devicesfor vitamin C. Int J
Pharm 2002; 242: 329-43.
10. Kristmundsdottir T, Gudmundsson OS, Ingvarsdottir K. Release of
diltiazem from eudragit microparticles prepared by spray-drying. Int J
Pharm 1996; 137: 159-65.
11. Cook RO, Pannu RK, Kellaway IW. Novel sustained release microspheres
for pulmonary drug delivery. J cont release 2005; 104(1): 79-90.
12. Moretti MDL, Gavini E, Juliano C, Pirisino G, Giunchedi P. Spray-dried
microspheres containing ketoprofen formulated into capsules and tablets. J
Microencapsul 2001; 18(1): 111-21.
7
9.
10.
11.
11.1
SIGNATURE OF THE
CANDIDATE
REG NO.
REMARKS OF THE GUIDE
NAME AND DESIGNATION OF
GUIDE
DR. PRAKASH RAO. B
Professor and HOD
Department of pharmaceutics, V.I.P.S.,
Bangalore-560070
SIGNATURE
11.2
HEAD OF THE DEPARTMENT
DR. PRAKASH RAO. B
Professor
Department of pharmaceutics, V.I.P.S.,
Bangalore-560070
SIGNATURE
12.
REMARKS OF THE PRINCIPAL
SIGNATURE WITH SEAL
8