M.Pham project presentation phase 2

FORMULATION AND EVALUATION OF
ARTEMETHER SUSTAINED RELEASE FLOATING
BILAYER TABLETS
Guided by,
DR. A. N. RAJALAKSHMI, M.Pharm., Ph.D.,
Prepared by,
P. DHANESHWAR, B.Pharm.,
DEPARTMENT OF PHARMACEUTICS
COLLEGE OF PHARMACY
MTPG & RIHS
1

CONTENTS
 Rationale behind the study
 Introduction
 Review of literature
 Drug profile
 Aim & objective of present study
 Plan of work
 Materials & Methods
 Results
 Optimisation of the formulation
 Conclusion
 References
2

 Artemether, an anti-malarial drug used in uncomplicated and severe
falciparum is 10-100 folds potent than other anti-malarials, however
due to rapid elimination resulting in poor efficacy it is combined
with other antimalarials like Lumefantrine (AL) but,
Artemether and Lumefantrine (AL) differ markedly in terms
of rate of absorption and elimination.
 Artemether undergoes absorbption rapidly in stomach, reaching a
peak concentration within two hours, but it has short biological half
life (2 to 3 hours) and hence gets completely cleared from the body
within 4 to 6 hrs of dosing.
 In contrast, Lumefantrine is absorbed and cleared more slowly
(Terminal elimination half-life of 3-4 days) hence remains even after
Artemether is completely cleared from the body and as a result
accumulates with successive doses.
4

 In context of the above principles, a strong need was recognized for a
system that resides and delivers Artemether in stomach (Gastric
retention).
 Rapid elimination resulting in poor bioavailability in conventional
dosage forms of Artemether necessitated the design and development
of a drug delivery system that delivers over a relatively longer period
of time (Sustained release).
Hence in the present study, an attempt has been made to
develop Floating Drug Delivery System of Artemether,
thereby increasing its gastric residence time and also
releasing it at a sustained fashion to ensure optimum
levels of the drug in the blood and minimizing its side
effects.
5

 One of the feasible approaches for achieving prolonged and
predictable drug delivery profile in GIT is to control gastric retention
time (GRT). Dosage forms with prolonged GRT overcome the
problems of simple sustained release dosage forms.
 GRDDS are dosage forms which prolong the retention time of a
drug in the GIT.
 Prolonged gastric retention improves bioavailability, reduces drug
waste, and improves solubility for drugs that are less soluble in a
high pH environment.
 It encompasses a variety of systems and devices such as floating or
Hydro dynamically balanced systems, raft systems, expanding
systems, swelling systems, bio-adhesive systems and low-density
systems.
GASTRORETENTIVE DRUG DELIVERY SYSTEMS
(GRDDS)
7

DRUG CANDIDATES FOR GASTRIC RETENTION
 Acting locally in the stomach (e.g. Antibiotics against H.Pylori,
Antacids and Misoprostol) and Unstable in the intestinal or
colonic environment such as Captopril.
 Absorbed incompletely due to a relatively narrow window of
absorption in the GIT,
Such as Cyclosporin, Ciprofloxacin, Furosemide, L-DOPA, P-
aminobenzoic acid and Riboflavin
 Exhibit low solubility at high pH values such as verapamil HCl,
Diazepam and Chlordiazepoxide.
DRUG NOT CANDIDATES FOR GASTRIC RETENTION
 Drugs that may cause gastric lesions, e.g., NSAIDS
 Drug substances that are unstable in the strong acidic
environment of the stomach, e.g.Erythromycin.
 Drugs having very limited acid solubility. e.g. Phenytoin
 Drugs that are used for selective release in the colon. e.g.
5- amino salicylic acid and corticosteroids 8

 Hydro dynamically balanced systems (HBS) incorporate buoyant
materials enabling the device to float, they could either be
effervescent or non effervescent systems.
 Raft systems incorporate alginate gels – these have a carbonate
component and, upon reaction with gastric acid, bubbles form in the
gel, enabling floating.
 Swelling type of dosage form swells to extent that prevents their
exit from the stomach through the pylorus. As a result, the dosage
form retained in the stomach.
 Bio/Muco-adhesive systems involve the use of bioadhesive
polymers that can be adhered to the epithelial surface of the GIT.
APPROACHES FOR GASTRIC RETENTION
9

 Modified shape systems are non-disintegrating geometric shapes
molded from silastic elastomer or extruded from polyethylene
blends.
 High-density formulations include coated pallets, having density
greater than 1. This is accomplished by coating the drug with a
heavy inert material such as Barium sulphate, ZnO, Titanium
dioxide.
Fig.1 Systems and devices for gastric retention 10

 Hydrodynamicaly balanced sysytems or Floating drug delivery
systems (FDDS) have a bulk density less than gastric fluids and so
remain buoyant in the stomach without affecting the gastric
emptying rate, for a prolonged period of time.
 While the system is floating on the gastric contents, the drug is
released slowly at the desired rate from the system.
 Floating systems can remain in the gastric region for several hours
and hence significantly increases the gastric residence time of drugs.
 Classification of HBS
Floating drug delivery systems are classified depending on the
use of formulation variables:
 Effervescent and
 Non-effervescent systems.
HYDRODYNAMICALY BALANCED SYSYTEMS
11

 Non-effervescent floating dosage forms use a gel forming or
swellable cellulose type of hydrocolloids, polysaccharides, and
matrix-forming polymers like polycarbonate, polyacrylate etc.,
 After oral administration this dosage form swells in contact with
gastric fluids and attains a bulk density of < 1, enables floating.
 Effervescent Systems are matrix type of systems prepared with the
help of swellable polymers such as methylcellulose, chitosan and
effervescent components like Citric acid & Sodium bicarbonate or
Tartaric acid and Sodium bicarbonate .
 They are formulated in such a way that when in contact with the
acidic gastric contents, CO2 is liberated and gets entrapped in
swollen hydrocolloids, which provides buoyancy to the dosage
forms.
12

SUSTAINED RELEASE EFFERVESCENT
FLOATING BILAYER TABLETS
 Sustained release effervescent floating bilayer tablet is composed of
two layers. A layer of sustained release polymer and drug
(Sustained release layer) and a layer of effervescent floating
components (Floating layer).
 Such a formulation offers more advantages compared to single
layer/matrix effervescent floating tablets in terms of stability. Since
effervescent components are unstable and incompatible with many
potential drug candidates for gastric retention, Hence such a
approach could be highly beneficial.
Fig 2. Sustained release bilayer floating system 13

 Hilton et al (1992) developed an oral sustained release floating
dosage form of Amoxicillin trihydrate. Various polymers including
sodium carboxy methylcellulose (SCMC) were investigated for
the evaluation of an oral sustained release floating dosage form of
Amoxycillin trihydrate, it was reported that SCMC containing
tablets quickly gelled, lost shape and floated on the surface of the
dissolution medium.
 Penners et al (1997) formulated an expandable tablet containing
mixture of polyvinyl lactams and polyacrylates that swell
rapidly in an aqueous environment and thus stays in stomach over
an extended period of time. In addition to this, gas-forming agents
were also incorporated so that the gas formed reduced the density of
the system rapidly. Thus the system tended to float on the gastric
environment quickly.
REVIEW OF LITERATURE
14

 Talwar et al (2001) developed a formulation for oral
administration of Ciprofloxacin. The formulation was composed of
Ciprofloxacin, sodium alginate, xanthum gum, sodium bicarbonate,
and cross- linked polyvinyl pyrrolidone. The hydrated gel matrix
created a diffusion path for the drug, resulting in sustained release of
the drug.
 Rajnikanth et al (2008) developed a floating in-situ gelling system
of Clarithromycin, for potentially treating gastric ulcers, associated
with Helicobacter pylori. The addition of sucralfate to the
formulation significantly suppressed the degradation of
Clarithromycin at low pH. Floating in-situ gelling system showed
a significant anti-Helicobacter pylori effect than that of
Clarithromycin suspension.
 Niranjan et al (2007) studied a bilayer tablet of Propranolol
hydrochloride using superdisintegrant sodium starch glycolate for the
fast release layer and water immiscible polymers such as
ethylcellulose, Eudragit RLPO and Eudragit RSPO for the
sustaining layer.
15

 Liandong Hu et al (2011) prepared floating matrix dosage form for
Dextromethorphan hydrobromide based on gas forming technique.
In vitro and in vivo evaluation in healthy human volunteers were
also conducted. The floating tablets were prepared using
hydroxypropyl methylcellulose as hydrophilic gel material, sodium
bicarbonate as gas generating agent and hexadecanol as floating
assistant agent. An orthogonal experimental design method was
employed to select the optimized formulation.
 Narendra et al (2006) developed an optimized gastric floating drug
delivery system containing Metoprolol tartrate as a model drug by
the optimization technique. A 23 factorial design was employed in
formulating the gastric floating drug delivery system with total
polymer content: drug ratio (X1), polymer: polymer ratio (X2) and
different viscosity grades of (HPMC) (X3) as independent variables.
The results indicate that X1 and X2 significantly affected the
floating time and release properties, but the effect of different
viscosity grades of HPMC (K4M and K10M) was non-significant.
Regression analysis and numerical optimization were performed to
identify the best formulation.
16

ARTEMETHER
Category Anti-malarial
Structural formula
Molecular formula C16H26O5
Chemical name Beta-Methylether of 11-epidihydroartemisinin
Molecular weight 298.3
Description White Crystalline powder
Melting point 142-1450c
Log P 2.6
18

Solubility : Insoluble in water , Freely soluble in ethyl acetate and very soluble in
dichloromethane and acetone.
Dose : For both uncomplicated and severe falciparum , dose schedule is 3.2 mg/kg
on day 1,followed by 1.6 mg/kg daily for up to 7 days.
Pharmacokinetic Parameters
Absorption Rapidly absorbed from GIT
Urinay Excretion < 0.5%
Vd (liters/kg) 2.2
Protein Binding 50%
Half-Life 2 – 3 hrs
Bioavailibility 50%
Nature Lipophilic
Clearance (ml/min) 250
19

AIM AND OBJECTIVE OF
PRESENT STUDY
20

AIM
 To Formulate Artemether sustained release floating bilayer tablets
and evaluate them to get an optimized formulation.
OBJECTIVE
 The main objective of this work is to minimize frequency of
administration, enhance the therapeutic efficacy and achieve better
patient compliance.
21

 Literature survey
 Selection of Drug and Polymers
 Pre-formulation studies of drug
 Design of experiment
 Pre-compression evaluation of blend
 Preparation of bilayer floating tablets
 Post compression evaluation of floating tablets
 Optimisation of the formulation and
 Response surface analysis
PLAN OF WORK
22

MATERIALS
Following chemicals were procured from SAIMIRRA INNOPHARM
PVT. LTD., AMBATTUR, CHENNAI.
 Drug: Artemether
 Polymers: HPMC K100M, Carbopol 934P
 Effervescent components: Sodium bicarbonate & Citric acid
 Other Excipients:
 Micro crystalline cellulose PH 101 & 102
 Xanthan gum
 PVP K30
 Aerosil
 Red oxide iron
 Magnesium Stearate
24

LIST OF EQUIPMENTS
UV Spectrophotometer
Systronic 1800 UV/Vis double beam
spectrophotometer, Japan
Tablet compression
machine
CLIT Single punch machine, Karnavati
Engineering ltd., Gujarat, India
Dissolution test apparatus
Dissolution test apparatus-EDT-08LX,
Electrolab, Mumbai, India
Analytical balance AUW220D, shimadzu, Japan
Friabilator
Roche Friabilator Camp-bell Electronics,
Mumbai, India
Hardness tester
Monsanto Hardness tester, Ketan
scientific industries, model-1101,
Mumbai, India
FTIR FTIR – 8400S model, Shimadzu(Japan)25

1. PRE-FORMULATION STUDIES OF DRUG
 Physical appearance
The appearance of the API was done by visual observation.
 Analytical method
Determination of λ max : UV spectrophotometric determination of
20µg/ml solution scanned in the range of 200 – 400 nm
Standard calibration grpah of Artemether:
Concentrations of 5 to 30 µg/ml solutions scanned at 256 nm.
 Compatibility study of drug and excipients :The FTIR spectras
were recorded for pure drug and physical mixture of drug &
excipients at the scanning range of 400-4000 Per cm.
METHODS
26

 Formulations were developed following a central composite design.
 The Design Expert Software (Version 7.1.6) suggested thirteen (13)
model formulations.
 In the study independent variables were concentration of Carbopol
934P (A) HPMC K100M (B) and dependent variables were total
floating time (TFT), and time for 95% release (T95). All other
formulation and processing variables were kept invariant throughout
the study.
 Table 1 and 2 summarizes an account of the all experimental runs,
Actual values and levels of independent variables.
2. DESIGN OF EXPERIMENT
27
Table 1: Maximum and minimum levels of independent variables
FACTOR NAME LOW LEVEL HIGH LEVEL
A CARBOPOL 45.0 75.0
B HPMC 30.0 90.0

RUN A: CARBOPOL B:HPMC
1 38.79 60
2 75 30
3 60 60
4 60 60
5 60 60
6 60 60
7 60 60
8 45 30
9 45 90
10 60 102.43
11 60 60
12 60 17.57
13 75 90
Table 2: DOE suggested by design expert in central composite design
(2-factor, 3-level) of Actual values of independent variables
28
 13 model formulations (Runs) were prepared by varying the
concentration of two independent variables as suggested above. All other
formulation and processing variables were kept invariant.

 Bulk density
Bulk density = Weight of the powder/Bulk volume of powder
 Tapped density
Tapped density = Weight of powder taken/ Tapped Volume
 Carr´s Compressibility index
Compressibility index (%) = ρt – ρo* 100 / ρt
Where ρt = Tapped density gram/ml, ρo = Bulk density gram/ml.
 Hausner’s ratio
Hausner ratio = Tapped density/Bulk density
 Angle of repose
tanθ = h/r
Where, h and r are the height and radius of the powder cone.
3. PRE-COMPRESSION EVALUATION OF BLEND
29

 Tablets were prepared by direct compression technology using clit
single punch machine.
 Bilayer floating tablets were prepared in two stages.
 First stage was formulation of floating layer. The ingredients such as
Magnesium stearate, xanthium gum, NaHCO3, Citric acid, Micro
crystalline cellulose, were mixed geometrically and compressed to
produce floating layer tablets.
 Second stage was formulation of bilayer floating tablets. The drug,
polymer, magnesium stearate were mixed separately for sustained
release layer.
 Floating layer was placed in punching die. Then the contents of
sustained release layer were placed over the floating layer and
compressed to produce bilayer floating tablets.
4. PREPARATION OF BILAYER FLOATING TABLETS
30

 Weight variation
20 tablets were weighed individually. Average weight was calculated
and the individual tablet weight to the average was compared.
 Thickness
Using vernier caliper in mm.
 Hardness
Using Monsanto hardness tester.
 Friability
Using Roche friabilator, % friability is calculated using,
% friability = (W1-W2)/W1*100
 In vitro buoyancy studies
The tablets were placed in 900 ml dissolution vessel containing 0.1N
HCl (pH=1.2). The time required for the tablets to rise to the surface
and the floating duration were determined as floating lag time and
total floating time respectively.
5. POST COMPRESSION EVALUATION
31

 Drug content
Accurately weighed 20 tablets were powdered and weighed a
quantity equivalent to 40 mg of drug and transferred to 100 ml
volumetric flask, 20 ml of 0.1 M Sodium hydroxide is added and
centrifuged for 5 minutes. The resultant supernatent solution is then
analyzed using UV Spectrophotometer at 256 nm.
 In vitro dissolution studies
Using USP type 2 apparatus at 37 ± 0.5 deg C and at 50 rpm and 0.1
N HCL (Ph 1.2) as dissolution media. The samples were removed at
predetermined intervals by maintaining sink condition. Each
removed samples is filtered by using 0.45μ filter. The samples were
analyzed at 256 nm for estimation of Artemether by UV/VIS
spectrophotometer.
 Release kinetics studies
The kinetics of drug relesase from tablets formulations were
determined by finding the R2 values for Zero order, first order, Hixon
crowell, Higuchi, Kors-meyer peppas plots.
32

1.1 Determination of Absorbance maxima
 Inference: Lambda max is observed at 256 nm
1.2 Standard graph of Artemether
 Inference: 5-30 µg/ml Sols. of Artemether obeys Beer-Lamberts law
1. PREFORMULATION STUDIES
0
0.1
0.2
0.3
0.4
0.5
0.6
0 10 20 30 40
ABSORBANCE
CONCENTRATION
34

1.3 Drug – Excipients compatibility studies
 The FTIR spectra of physical drug-excipients mixture showed
neither appearence nor disappearance of characteristic peaks when
compared with FTIR spectrum of pure sample suggesting that there
was no interaction between drug and excipients and drug was stable
without undergoing any physical change.
35

 Across all formulations, blends showed compliance in terms of
flow property (Good) and compressability within specified limits.
2. PRE COMPRESSION PARAMETERS
CODE
Bulk density
(gm/cc)
Tapped density
(gm/cc)
Angle of
repose
CI
(%)
Hausner’s
ratio
F1 0.57 0.68 43.15 16.17 1.19
F2 0.47 0.73 41.81 35.61 1.55
F3 0.54 0.72 28.60 18.51 1.29
F4 0.58 0.78 27.34 10.00 1.34
F5 0.56 0.78 40.10 28.20 1.39
F6 0.58 0.77 48.23 24.67 1.32
F7 0.58 0.70 26.56 17.14 1.20
F8 0.61 0.72 32.46 15.20 1.18
F9 0.56 0.78 40.10 28.20 1.39
F10 0.57 0.68 43.15 16.17 1.19
F11 0.54 0.72 28.60 18.51 1.29
F12 0.56 0.78 40.10 28.20 1.39
F13 0.58 0.70 26.56 17.14 1.20
36

3. POST COMPRESSION PARAMETERS
3.1 Physical evaluation
CODE
Thickness
(mm)
Hardness
(kg/cm2)
Friability
(%)
Uniformity of
wt (mg)
Drug content
F1 2.5 3.2 0.89 600±5% 98.35
F2 2.6 3.3 0.76 600±5% 97.88
F3 2.5 3.8 0.72 600±5% 99.20
F4 2.61 3.8 0.40 600±5% 99.20
F5 2.5 4.3 0.43 600±5% 99.20
F6 2.43 2.9 0.12 600±5% 99.12
F7 2.64 3.3 0.10 600±5% 102.3
F8 2.62 3.4 0.21 600±5% 105
F9 2.64 3.9 0.13 600±5% 101.55
F10 2.66 4 0.36 600±5% 100
F11 2.61 4 0.12 600±5% 99.80
F12 2.59 4 0.10 600±5% 99.23
F13 2.5 4.3 0.10 600±5% 99.69
 Across all formulations, tablets showed compliance in terms of
mechanical strength and drug content within acceptable
pharmacopoeial limits.
37

3.2 In Vitro Buoyancy Studies
FORMULATION
CODE
FLOATING
LAG TIME
(Sec)
TOTAL
FLOATING
TIME (Hours)
F1 59 4
F2 45 12
F3 48 11
F4 50 9
F5 51 9
F6 53 9
F7 51 9
F8 58 6
F9 56 6
F10 52 9
F11 55 9
F12 56 9
F13 45 12
 Among the various formulations, F2 and F13 remained buoyant
throughout the study (12hours) with minimum floating lag time (45
Seconds).
38

3.3 In Vitro Drug release
TIME
HOURS
F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 F11 F12 F13
0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 18.3 26.2 24.5 25.5 25.1 24.4 35.8 24.0 13.3 24.9 25.1 43.2 28.1
2 29.2 48.5 32.4 32.3 33.5 31.1 49.6 32.8 18.3 32.5 33.5 67.9 36
3 38.5 67.8 36.3 38.5 41.2 36.1 69.2 40.5 26.2 36.9 41.2 95.1 40.5
4 48.9 95.2 44.4 54.2 49.3 48.9 95 46.9 32.5 44.1 49.3 51.7
5 55.4 59.7 62.5 63.3 56.9 54.2 38.9 49.5 53.3 59
6 61.9 63.8 67.1 79.7 65.6 60.8 45.4 63.2 59.7 68.5
7 69.4 73.7 76.4 85.7 71.0 65.7 51.9 73.9 65.7 72
8 77.8 81.3 82.9 91.6 83.9 70.9 61.4 81.5 71.6 82.5
9 95.3 95.3 96.9 95.2 95.5 76.2 67.8 95.3 75.2 88.8
10 80.8 75.3 82.4 91.7
11 85.7 81.9 87.1 94.2
12 95.1 89.3 95.4 98.3
13 95.1
 All the formulations showed more than 12% drug release within 1hour, After 12
hours study, it was found that formulations F8, F11 and F13 released more than 95% of
drug (HPMC 90 mg) and formulations F2, F8 and F12 released 95% of drug within 5
hours (with HPMC<35mg). The formulation F13 containing maximum amount of
HPMC K100M and Carbopol 934P showed maximum drug release of 98.3% compared39

3.4 Drug release kinetics
FORMULATION
CODE
R² VALUES
Zero order First order Higuchi Peppas Hixson
F1 0.943 0.987 0.995 0.931 0.977
F2 0.979 0.010 0.967 0.910 0.002
F3 0.910 0.949 0.963 0.849 0.943
F4 0.919 0.969 0.975 0.872 0.958
F5 0.943 0.916 0.951 0.941 0.853
F6 0.925 .966 0.972 0.862 0.959
F7 0.942 0.006 0.971 0.846 0.000
F8 0.932 0.982 0.997 0.881 0.970
F9 0.984 0.994 0.963 0.926 0.993
F10 0.925 0.947 0.973 0.842 0.948
F11 0.912 0.972 0.998 0.868 0.956
F12 0.982 0.024 0.977 0.809 0.044
F13 0.932 0.973 0.984 0.857 0.968
 R2 value of Higuchi’s model is very near to one for all most all 13
formulations compared to the R2 values of other kinetic models. Thus,
it can be concluded that the drug release follows Higuchi’s release
mechanism.
40

 The Design Expert Software suggested thirteen (13) model
formulations.
 In the study independent variables were concentration of Carbopol
934P (A) HPMC K100M (B) and dependent variables were total
floating time (TFT), and time for 95% release (T95). All other
formulation and processing variables were kept invariant throughout
the study.
 The resulting data (Experimental values of dependent variables for
all 13 model formulations in their respective units) was fitted into
Design Expert Software and analyzed statistically using analysis of
variance (ANOVA).
SUGGESTED SOLUTION:
No. CARBOPOL HPMC TFT RELEASETIME DESIRABILITY
1 75.00 90.00 11.2809 12.071 0.909
42

 The data (Experimental values of dependent variables for all 13
model formulations in their respective units) was also subjected to 3-
D response surface analysis to determine the influence of
independent variables over responses.
 Figure below shows the 3D response surface plot to determine the
effect of amount of HPMC K 100M and Carbopol over total floating
time.
 It can be infered from the plot that increasing the concentration of
Carbopol increases the total floating time and it may be due to the
hydrophilic nature of Carbopol which produces easy swelling of tablets.
44

 Figure below shows the 3D response surface plot to determione the
effect of amount of HPMC K 100M and Carbopol over total release
time.
From the 3D surface plots it is evident that the effect of HPMC K100M
seems to be more pronounced in case of release time and Carbopol
plays no part in it and in case of Total floating time Carbopol
exclusively plays the part and there is no effect of HPMC K100M
over it.
45
 It can be infered from the plot that increasing the concentration of HPMC
increases the total RELEASE TIME and it may be due to the kinematic
viscosity offered by HPMC during drug release.

 Formulation of floating bilayer tablets containing Artemether as
sustained release for enhanced gastric residence time and improved
bioavailability and evaluation of the formulations F1 to F13 for
desired drug release and other post compression parameters has been
carried out.
 Central composite design was applied to investigate the combined
effect of formulation variables and for product optimisation. From
the optimization study it was found that the formulation F13 gives
the best result in terms of the lag time (45 seconds) and drug release
(more than 95% at the end of 12 hours) with sustained drug release
rates.
 It is concluded from the present investigation that effervescent based
floating drug delivery is a promising approach to achieve in vitro
buoyancy by using hydrocolloid forming Carbopol 934P polymer
and gas generating agents sodium bicarbonate and citric acid. HPMC
(K100M) containing floating bilayer tablets of Artemether is a
promising sustained release system for the effective treatment of
malaria. 47

REFERENCES
• Bolton S, Desai S; Floating sustained release therapeutic compositions; US
Patent; 4,814, 179; March 21; 1989.
• Desai S.A; Novel Floating controlled release drug delivery system based on
a dried gel matrix Network (master’s thesis) Jamaica; NY: St. John’s
University; 1984.
• Iannuccelli V, Coppi G, Sansone R and Ferolla G; Air-component multiple-
unit System for prolonged gastric residence, Part-II, In-vivo evaluation;
International Journal of Pharmaceutics; 1998; 174(1-2).
• Ichikawa M; A new multiple unit dosage forms: Preparation and in vitro
evaluation of floating and sustained release characteristics with p-
aminobenzoic acid and isosorbide dinitrate as model drugs; Journal of
pharmaceutical science; 1991; 80; 1062-1066.
• Nur A.O, Zhang J.S; Captopril floating and/or bioadhesive tablets: design
and release kinetics; Drug Development & Industrial pharmacy; 2000; 26;
965-969.
• Ozdemir N.L, Ordu S, Ozkan Y; Studies of floating dosage forms of
furosemide: in vitro and in vivo evaluation of bilayer tablet formulation;
Drug Development & Industrial pharmacy; 2000; 26; 857-866.
• Xu W.L, Tu X.D, Lu Z.D; Develpoment of Gentamycin sulfate sustained
release tablets remaining-floating in stomach; AAPS Pharm Tech;1991;
26(7); 541-545. 48

PUBLICATIONS
 A Review article on “Sustained release effervescent floating bilayer
tablets: A Review of novel approach” is to be published in Pharama
Infopedia Magazine 2017 Volume 5, Issue 8 (August).
 A Research article named “Formulation, Evaluation and
Optimisation of sustained release bilayer floating tablets of
Artemether’’ is to be published in European Jounal of
Pharmaceutical and Medical Research (UGC APPROVED)
2017 August issue.
49

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