This document summarizes a research study on the design of bilayer floating films for delivery of propranolol hydrochloride and rosuvastatin calcium. The study aimed to develop a single dosage form to provide therapeutic effects for hypertension and hyperlipidemia simultaneously. Various polymers and plasticizers were evaluated for their effects on film properties and drug release. Bilayer films were prepared using solvent casting method, with an immediate release layer of rosuvastatin and a sustained release layer of propranolol. The films were characterized for drug content, floating behavior, drug release and stability studies. The bilayer floating film system showed potential for gastroretention and controlled delivery of both drugs for cardiovascular diseases.

1. Design of gastroretentive bilayer floating films of
propranolol hydrochloride and rosuvastatin calcium.
Presented by,
Mr. Namdeo G. Shinde
B. Pharm.
Under the guidance of,
Dr. N. H. Aloorkar
M. Pharm. Ph. D
Satara College of Pharmacy, Degaon-Satara.
2013-2014.

2. CONTENTS
Introduction
Need of present investigation
Literature survey
Material and methods
Results and discussion
Conclusion
Future perspectives
References

3. INTRODUCTION
The goal of any drug delivery system is to provide a therapeutic
amount of drug to proper site in the body to achieve and maintain
therapeutic concentration within range and to show pharmacological
action with minimum incidence of adverse effects.
To achieve this goal one should maintain dosing frequency and suitable
route of administration.
-Oral, parenteral, topical, nasal, rectal, vaginal, ocular etc.
Out of these routes, oral route of drug delivery is considered as the
most favored route of drug delivery, because of ease of
administration, more flexibility in designing, ease of production
and low cost.

4. -Physiological difficulties:
Inability to restrain and locate the controlled drug delivery system
within the desired region of the GIT due to variable gastric emptying
and motility.
Phases of migrating myoelectric cycle (MMC)
Phase I Phase lasts for 40-60 min. with rare contractions.
Phase II
(Pre-burst phase)
Phase lasts for 40-60 min.
Intensity and frequency increases gradually.
Phase III
(burst phase)
Phase lasts for 4-6 min. It includes intense and regular contractions for
short period. It is also known as the housekeeper wave.
Phase IV Phase lasts for 0-5 min and occurs between phases III and I of two
consecutive cycles

5. The real challenge in development of oral controlled release drug
delivery system is to sustain the release as well as prolong the
presence of dosage form in stomach or upper small intestine until
drug is completely released in desired period of time from suitable
formulation.
Gastroretentive system can remain in the gastric region for several
hours and hence significantly prolongs gastric residence time of drug
which improves bioavailability.
To provide good floating behavior in the stomach the density of
system should be less than density of gastric contents
(~ 1.004 g/cm3).

6. Advantages of GRDDS
Improved drug absorption
Controlled delivery of drugs
Treatment of gastrointestinal disorders
Site-specific drug delivery
Ease of administration and better patient compliance
Simple and conventional equipments are required for manufacturing

7. Limitations of GRDDS
 It is not a suitable system for drugs with stability or solubility
problem in stomach.
 FDDS require sufficiently high level of fluid in the stomach.
 Drugs having irritant effect on gastric mucosa are not suitable.
 Retention of high-density systems in the antrum part under the
migrating waves of the stomach is questionable.

8. STRATEGIES FOR GASTRORETENTION
Low density systems (<1.004 g/cm3)
High density systems (3 g/cm3)
Mucoadhesive systems
Superporous hydrogels
Expandable/swelling systems (12-18mm)
Magnetic systems

9. Superporous hydrogels
Swelling system Gastroretentive floating film
Gas generating system

10. Floating film delivery system
 Emerged as an advanced alternative to traditional dosage forms
 Floating film is drug loaded polymeric film consisting of an active
pharmaceutical ingredient, polymers, film forming agent, plasticizer
and suitable solvent.
Advantages-
Preparation of film is simple
Time saving
Chances of cross contamination are very less
Handling of film is easy

11. Preparation:
Solvent evaporation method
Drug release profile can be modified by using different polymers.
Layer-by-layer film formulation technique in which one layer is
of controlled release polymer and another layer is of sustained release
polymer can be prepared.
1
• Polymeric dispersion of drug and
polymer
2
• Poured in petriplate and dried
3
• Thin layered film

12. Film forming polymers in floating films:
 Provide quick disintegration and mechanical strength to the films.
Examples- pullulan, gelatin, guar gum, xanthan gum, hydroxyl propyl
methylcellulose, modified starches.
Ideal properties of the polymers used in the film drug delivery:
Non-toxic, non- irritant
Low density and readily available
Sufficient shear and tensile strength and shelf life.

13. Plasticizers used in floating films:
It helps to improve the flexibility of the film and reduces the
brittleness of the film.
Plasticizer significantly improves the film properties by reducing the
glass transition temperature of the polymer.
Examples-
Glycerol, propylene glycol, low molecular weight polyethylene
glycols, citrate derivatives like triacetin, acetyl citrate, phthalate
derivatives like dimethyl, diethyl, dibutyl derivatives, etc.

14. NEED OF PRESENT INVESTIGATION
Cardiovascular diseases (CVDs) are the number one cause of death.
According to the WHO Report 2012, CVDs will be the largest cause of
death and disability in India by 2020.
Hypertension and hyperlipidemia are the major disorders of the
cardiovascular system.

15. A strong need was recognized for the design of a single dosage form
which will give therapeutic effects on two or more diseases like
hypertension and hyperlipidemia simultaneously.
Hence to deliver propranolol HCl and rosuvastatin calcium
in the stomach, bilayer floating film was prepared.

16. Objectives
To formulate gastroretentive bilayer floating films of propranolol
HCl and rosuvastatin calcium.
To investigate the effect of polymer and plasticizer on the film.
UV-Spectroscopic simultaneous estimation of propranolol HCl and
rosuvastatin calcium in pure drug and in bilayer film.
To evaluate gastroretentive bilayer floating films of propranolol
HCl and rosuvastatin calcium.

17. Kumar MP et al (2010) have studied the gastroretentive delivery of
mucoadhesive films containing pioglitazone using ethyl cellulose as a
rate controlling polymer, HPMC and carbopol-934 were used as
mucoadhesive polymers.
They found that the polymer concentration was a major factor
affecting the drug release and mucoadhesive strength of film.
Literature review

18. Patel N et al (2011) have carried out formulation and evaluation of
floating tablets of metoprolol tartrate. They prepared tablets by using
MCC, HPMC K100M and HPMC K4M as polymers and sodium
bicarbonate as a gas-generating agent.
From this, they concluded that the floating tablets of metoprolol
tartrate could retard the release of drug upto a period of 8 hours.
Literature review

19. Literature review
Bhosale UV et al (2012) have studied the effect of concentration and
viscosity grade of polymer on drug release. They used hydroxypropyl
methylcellulose of different viscosity grades (HPMC K4M, HPMC
E5LV, HPMC K100M) as polymer and sodium bicarbonate as a gas-
generating agent to reduce floating lag time.
They concluded that as the viscosity and concentration of the
polymer was increased, drug release was decreased.

20. Brahmaiah B et al (2013) have formulated and evaluated of
gastroretentive floating drug delivery system of metoprolol tartarate.
They prepared floating tablets using HPMC K4M and HPMC K100M
as the release retardant polymers.
From this, they concluded that the floating tablets could control the
fluctuations in the plasma drug concentration, increased the
gastric residence time and eventually improved the bioavailability
of the drug.
Literature review

21. DRUG PROFILE
Propranolol Hydrochloride
Propranolol hydrochloride is non-selective beta-adrenergic receptor
blocking agent. It is white crystalline solid readily soluble in water and
ethanol.
Brandname Manufacturer Brandname Manufacturer
Beptazine MM Labs Inderal ® LA Wyeth pharmaceuticals
Betaprp- DZ Concern pharma. Pr Inderal ® LA Pfizer
Ciplar H Cipla Ltd. Propranolol hcl oral solution Roxane labs.
Corbetazine Nicholas piramal Inderal ® Akrimax pharmaceuticals
Dizepax Unimark pharma Tensyn plus Synokem pharmaceuticals
Syziral Psyco remedies Innopran XL Reliant pharmaceuticals

22. PKa: 9.4
Melting point: 162-165°C
Molecular formula: C16H21NO2.HCl
Molecular weight: 295.80
Pharmacokinetics-
Propranolol is completely absorbed after oral administration.
Due to first pass metabolism bioavailability is less (25%).
Peak plasma concentration occur about 1 to 4 h after an oral dose.
About 90 % of circulating propranolol is bound to plasma proteins.
Propranolol is extensively metabolized in kidney.
OCH2CHOHCH2NHCH(CH3)2 . HCl
2-Propranol,1-[(1-methylethyl)amino]-3-(1-napthalenyloxy)-hydrochloride

23. Rosuvastatin Calcium
Rosuvastatin calcium is a synthetic lipid-lowering agent.
Rosuvastatin is an inhibitor of HMG-CoA reductase. This enzyme
catalyzes the conversion of HMG-CoA to mevalonate, an early and
rate-limiting step in cholesterol biosynthesis.
Brand
names
Dose
(mg) Manufacturers
Brand
name
Dose
(mg) Manufacturers
Bestor 5,10 Biocon Ltd. Rozavel 5,10 Sun pharmaceuticals
Fortius 5,10,20 Nicholas piramal Rozucor 5,10 Torrent pharmaceuticals
Ldnil FC 10,20 Saremed Ltd. Rostar 5,10 Vencare formulations Ltd.
Novastat 5,20 Lupin Turbovas 5,10 Microlabs Ltd.
Razel 5,10,20 Glenmark Zyrova 5,10 Zydus Cadila healthcare
Suvalip 5,10 Orchid chemicals Rovalip 10 Cadila pharmaceuticals
Rosuvas 5,10,20 Ranbaxy Rosuvastat 10 Dr. Reddys Lab.

24. Treatment LDL reduction HDL increase
Atorvastatin (10-80 mg) 37-51 % 5.7-2 %
Simvastatin (10-80 mg) 28-46 % 5.3 -6.8 %
Rosuvastatin (5-40 mg) 46-55 % 7.6-9.6 %
Pravastatin (10-40 mg) 20-30 % 3.2-5.5 %
Effect of drugs on LDL and HDL levels
PKa: 4.6
Melting point: 151-156°C
Molecular formula: (C22H27FN3O6S)2.Ca
Molecular weight: 1001.14°C
N
NN
SO2Me
O-
OH
OH O
F
Ca2+
Bis[(E)-7-[4-(flurophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]
pyrimidin-5-yl]-(3R,5S)-3-5-dihydroxyhept-6-enoic acid] calcium salt
2

25. MATERIALS AND METHODS
Propranolol hydrochloride and rosuvastatin calcium were supplied by
Watson Pharma, Mumbai and Okasa Pharma, Satara respectively. HPMC
K4M, HPMC E5LV, Eudragit RS 100, dibutyl phthalate were procured
from Research-Lab Fine Chemicals, Mumbai.
Sr.
No.
Name of Equipments Manufacturer
1. Electronic balance AW 220, Shimadzu, Japan
2. UV Spectrophotometer Pharmaspec 1700, Shimadzu , Japan
3. Hot air oven Singhla Scientific, Ambala Cantt
4. Magnetic stirrer Remi Equipments, Mumbai
5.
USP tablet dissolution
apparatus
Electrolab, TDT- 08L, Mumbai, India
6.
Fourier transform infrared
spectrophotometer (FTIR)
Alpha Bruker, Germany
7.
Differential scanning
calorimeter
Mettler- Toledo, Switzerland

26. Methods:
Selection of Drug:
Propranolol hydrochloride-
It was decided to formulate it in gastroretentive dosage forms because
it has short half-life (1-4 h), has less oral bioavailability (25%).
Rosuvastatin calcium-
From literature survey it was found that rosuvastatin calcium causes
more decrease in cholesterol than any other statins. Its absolute
bioavailability is 20 %. The half-life is 19 h.

27. Selection of Polymers and Excipients:
HPMC K4M polymer is hydrophilic in nature and has good gelling
properties hence suitable for use in sustained release layer.
HPMC E5LV mainly cause rapid release of drug because of its low
viscosity hence suitable for incorporation in immediate release layer.
Eudragit RS-100, a polymethacrylate, was used as water insoluble film
former in sustained release layer and drug release retardant.
Dibutyl phthalate was used as a plasticizer. Water and ethyl alcohol
were used as solvents.

28. Sr. No. Ingredients Category
1. Rosuvastatin calcium API
2. Propranolol hydrochloride API
2. HPMC K4M, HPMC E5LV Hydrophilic polymers
3. Eudragit RL-100 Film former and drug release retardant
4. Dibutyl phthalate Plasticizer
5. Ethanol Solvent for Eudragit RS-100
6 Water Solvent for HPMC K4M and HPMC E5LV
FORMULATION INGREDIENTS

29. Preformulation Study:
Characterization of drug:
 Solubility profile
 Melting point of drug
 λ max determination and calibration curve of propranolol
hydrochloride and rosuvastatin calcium
Compatibility study between drug and excipients:
 DSC Study
 IR spectroscopy

30. Ingredients
Formulation codes
RP1 RP2 RP3 RP4 RP5 RP6 RP7 RP8 RP9
Immediate Release layer R1 R2 R3 R4 R5 R6 R7 R8 R9
Rosuvastatin calcium 5 5 5 5 5 5 5 5 5
HPMC E5LV 15 15 15 20 20 20 25 25 25
Dibutyl phthalate 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.50
Ethanol: Water 3:4 3:4 3:4 3:4 3:4 3:4 3:4 3:4 3:4
Sustained Release layer P1 P2 P3 P4 P5 P6 P7 P8 P9
Propranolol hydrochloride 40 40 40 40 40 40 40 40 40
HPMC K4M 20 20 20 25 25 25 30 30 30
Eudragit RS 100 04 06 08 04 06 08 04 06 08
Dibutyl phthalate 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5
Ethanol: Water 3:7 3:7 3:7 3:7 3:7 3:7 3:7 3:7 3:7
FORMULATION TABLE

31. Preparation of films
 Films with single and double layer were prepared by solvent
casting method.
Preparation of solution for immediate release (IR) layer:
Polymeric dispersion were prepared by dissolving HPMC E5LV in
distilled water with constant stirring (300-350 rpm) on magnetic
stirrer.
Rosuvastatin calcium was separately dissolved in ethanol: water
(3:1) and added in polymeric solution followed by addition of
dibutyl phthalate as plasticizer.
Final solution was stirred vigorously on magnetic stirrer
(600-650 rpm) for 5 min.

32. Preparation of sustained release (SR) layer:
HPMC K4M and Eudragit RS 100 were individually dissolved in
distilled water and ethanol respectively.
Propranolol hydrochloride was dissolved in little quantity of water
and slowly added in polymeric dispersion followed by addition of
dibutyl phthalate as plasticizer with vigorous stirring on magnetic
stirrer (300-350 rpm).

33. Preparation of bilayer film:
Firstly solution of sustained release (SR) layer was casted on
petriplate and allowed to dry naturally (35-40 0C) at least for
40 min. then solution of immediate release layer (IR) was casted on
the dried film of CR layer and allowed to dry for at least 50 min.
naturally followed by drying in hot air oven at 45-50 0C for
30-60 min.
On removal, the films were checked for possible imperfections
before being cut into 3×2 cm rectangles and stored.

34. Evaluation of gastroretentive drug delivery system
Visual appearance, thickness and weight of film
Folding endurance of film
Tensile strength of film
Percent moisture absorption study
Swelling index
Drug content and dissolution:
1 Apparatus USP Type II
2 Volume of medium 900 ml
3 Temperature 37±0.50C
4 Paddle Speed 50 rpm
5 Dissolution medium used 0.1 M HCl

35. Quantitative estimation of propranolol hydrochloride and
rosuvastatin calcium by UV spectroscopy
If the sample contain two absorbing drugs each of which absorb at
λmax of the other, it may be possible to determine both drugs by
Vierodt’s method.
Simultaneous estimation of two drugs can be possible only when
λmax of both drug components are reasonably dissimilar and two
components do not interact chemically.
It is calculated by formula,
𝑪𝒑𝒓𝒐 =
𝑨 𝟐 𝒂𝒚 𝟏 − 𝑨 𝟏 𝒂𝒚 𝟐
𝒂𝒙 𝟐 𝒂𝒚 𝟏 − 𝒂𝒙 𝟏 𝒂𝒚 𝟐

36. Where as,
ax1 and ax2 are absorptivities of PRO at λ1 and λ2 respectively.
ay1 and ay2 are absorptivities of ROS at λ1 and λ2 respectively.
A1 an A2 are absorbance of sample at λ1 and λ2 respectively.
𝑪𝒓𝒐𝒔 =
𝑨 𝟏 𝒂𝒙 𝟐 − 𝑨 𝟐 𝒂𝒙 𝟏
𝒂𝒙 𝟐 𝒂𝒚 𝟏 − 𝒂𝒙 𝟏 𝒂𝒚 𝟐

37. RESULTS AND DISCUSSION:
Preformulation Studies:
Solubility of drug:
 Rosuvastatin calcium:
Freely soluble in ethanol, methanol, slightly soluble in water
 Propranolol hydrochloride:
Freely soluble in water, ethanol, methanol etc.
Melting Point of propranolol hydrochloride and rosuvastatin
calcium: Name of drug Melting point in OC
(Test compound)
Melting point in OC
(Literature value)
Propranolol hydrochloride 159-161 162-165
Rosuvastatin calcium 152-154 151-156

38. λ max determination:
Propranolol hydrochloride
(289 nm)
Rosuvastatin calcium
(240.5 nm)

39. Calibration curve of propranolol hydrochloride
Concentration
(µg/ml)
Absorbance
0 0.0000
4 0.1561
8 0.2946
12 0.4452
16 0.5874
20 0.7443
24 0.8389
28 0.9542
32 1.163
36 1.2895
40 1.3726
λmax 289 nm
Slope 0.0347075
Intercept 0.019104545
Correlation coefficient 0.998617469
Beers range 4-40 µg/mi
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
0 4 8 12 16 20 24 28 32 36 40
Absorbance Concentration (µg/ml)

40. Calibration curve of rosuvastatin calcium
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 6 12 18 24 30 36
Absorbance
Concentration (µg/ml)
Concentration
(µg/ml)
Absorbance
0 0.000
6 0.223
12 0.4452
18 0.6129
24 0.7962
30 0.9876
36 1.2976 λmax 240.5 nm
Slope 0.034363
Intercept 0.004679
Correlation coefficient 0.996826
Beers range 6-36 µg/ml

41. Drug and polymer compatibility:
Fourier transform infrared spectroscopy (FTIR):
Sr. No.
Wave number
(cm-1) for drug
Group responsible
Propranolol hydrochloride (E)
1. 798 Α-substituted naphthalene (790 cm-1)
2. 1264 Aryl O-CH2 asymmetric stretch
3. 1030 Aryl O-CH2 symmetric stretch (1035 cm-1)
4. 2962 C-H stretching (3000-2950 cm-1)
Rosuvastatin calcium (D)
5. 2822 N-H stretching
6. 1732.13 C=O stretching
7. 1544 C=C stretching
8. 2922.25 C-H stretching (3000-2950 cm-1)
9. 1433 N-H bending
10. 1430 Asymmetric bending vibration of CH3 group
11. 1379 Symmetric bending vibration of CH3 group
12. 1328 Asymmetric vibration for S=O
13. 774 , 588, 488 C=C of benzene ring
14. 1227 Bending vibration for C-H
15. 1150 C-F stretching vibrations
A) Eudragit RS100 B) HPMC K4M,
C) HPMC E5LV D) Rosuvastatin calcium,
E) Propranolol hydrochloride,
F) Physical mixture of drug and polymer,
G) Representative formulation

42. Differential Scanning Calorimetry (DSC):

43. UV spectrophotometric method:
UV spectrophotometric method was used for simultaneous
quantitative determination of propranolol hydrochloride and
rosuvastatin calcium in bulk and pharmaceutical dosage form.
Absorptivity of propranolol
hydrochloride
Absorptivity of rosuvastatin
calcium
289 nm
(ax1)
240.5 nm
(ay1)
240.5 nm
(ax2)
289 nm
(ay2)
Mean (n=3) 228.6 298.8 378.3 103.0
± SD 1.000 0.5859 1.336 1.261

44. Batch
code
Visual
appearance
Wt. of films
(mg)
Film thickness
(m)
Folding
Endurance
Tensile
strength (%)
Moisture
uptake study
RP1 Opaque 91.74±0.23 16.66±0.57 308±2.00 57.26 1.15±1.02
RP 2 Opaque 92.69±0.23 17.50±0.50 291±3.60 59.23 1.60±0.60
RP 3 Opaque 92.85±0.17 17.33±0.57 271±2.52 59.93 2.41±0.69
RP 4 Opaque 117.07±0.23 20.56±0.51 265±2.08 60.07 2.08±0.96
RP 5 Opaque 117.17±0.96 20.66±0.57 259±2.65 60.26 2.77±0.57
RP 6 Opaque 118.23±0.32 20.33±0.15 249±1.53 60.81 2.41±0.66
RP 7 Opaque 124.20±0.40 22.86±0.87 232±3.51 61.12 5.05±0.46
RP 8 Opaque 127.13±0.59 22.00±1.00 217±3.06 61.31 6.98±0.42
RP 9 Opaque 127.21±0.50 23.29±0.61 205±3.00 62.09 7.86±0.80
Evaluation of gastroretentive floating bilayer films

45. 0 25 50 75 100 125 150
RP1
RP2
RP3
RP4
RP5
RP6
RP7
RP8
RP9
Film weight (mg)Formulationcode
14
16
18
20
22
24
26
RP1
RP2
RP3
RP4
RP5
RP6
RP7
RP8
RP9
Film thickness (µm)
Formulationcode
Weight of film
Thickness of
film

46. R
P
1
R
P
2
R
P
3
R
P
4
R
P
5
R
P
6
R
P
7
R
P
8
R
P
9
50
55
60
65
70
Formulation code
Tensilestrength
Folding endurance
Tensile strength
0
50
100
150
200
250
300
350
RP1 RP2 RP3 RP4 RP5 RP6 RP7 RP8 RP9
Foldingendurance
Formulation code

47. RP1
RP2
RP3
RP4
RP5
RP6
RP7
RP8
RP9
0
2
4
6
8
10
Formulation code
%Moistureabsorption
Percent moisture
absorption
0 2 4 6
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5 RP1
RP2
RP3
RP4
RP5
RP6
RP7
RP8
RP9
Time (h)
Swellingindex
Swelling index

48. Batch RP1 RP2 RP3 RP4 RP5 RP6 RP7 RP8 RP9
Immediate release (IR) layer: Rosuvastatin calcium
Batch R1 R2 R3 R4 R5 R6 R7 R8 R9
% content 97.5±0.74 101.6±0.25 103.1±0.57 100.26±0.92 104.34±0.81 102.3±0.66 100.12±0.11 102.33±0.53 104.27±0.34
Sustained release (SR) layer: Propranolol hydrochloride
Batch P1 P2 P3 P4 P5 P6 P7 P8 P9
% content 102.7±0.59 99.40±0.61 101.5±0.83 104.40±0.57 99.60±0.29 97.5±0.67 99.70±0.73 97.00±0.26 98.80±0.57
Drug Content:

49. In-vitro drug release:
Immediate release (IR) layer (Rosuvastatin calcium)
Time R1 R2 R3 R4 R5 R6 R7 R8 R9
1min 4.4±0.56 10.8±0.6 10.0±0.57 4.2±0.66 30.0±0.42 10.4±0.2 12.6±0.5 16.4±0.5 10.4±0.5
2 min 28.8±0.44 26.4±0.5 38.6±0.66 30.0±0.6 42.0±0.57 31.4±0.6 43.4±0.6 46.8±0.3 33.2±0.8
3 min 44.0±0.66 58.8±0.2 51.2±0.54 37.6±0.7 71.0±0.66 52.2±0.4 76.8±0.2 59.6±0.7 78.2±0.6
4 min 48.6±0.58 66.0±0.4 75.41±0.5 55.2±0.6 76.8±0.24 75.4±0.6 79.6±0.5 74.6±0.6 93.6±0.4
5 min 77.4±0.66 97.6±0.66 97.6±0.42 90.4±0.84 97.0±0.23 94.6±0.57 93.8±0.45 87.2±0.82 100.8±0.4
6 min 94.0±0.57 99.4±.44 99.4±0.66 99.0±0.57 103.8±0.4 101.4±0.5 99.0±0.47 101.4±0.2 102.8±0.1
0.0 1.5 3.0 4.5 6.0
0
10
20
30
40
50
60
70
80
90
100
110
R1
R2
R3
R4
R5
R6
R7
R8
R9
Time (Min.)
%Drugrelease

50. Sustained release (SR) layer (Propranolol hydrochloride)
P1 P2 P3 P4 P5 P6 P7 P8 P9
1h 47.9±0.66 39.2±0.42 35.4±0.64 44.6±0.56 38.4±0.42 31.8±0.53 52.6±0.74 51.5±0.68 38.5±0.37
2h 51.40±0.2 49.2±0.92 42.1±0.57 51.5±0.37 51.7±0.57 46.5±0.14 62.7±0.42 60.6±0.94 45.4±0.66
3h 57.7±0.76 50.3±0.35 47.7±0.34 55.3±0.74 59.2±0.66 48.2±0.12 66.8±0.94 65.0±0.47 52.8±0.43
4h 61.8±0.38 61.1±0.57 59.6±0.84 66.0±0.42 62.5±0.24 52.2±0.46 73.8±0.35 74.3±0.57 60.2±0.34
5h 72.8±0.56 67.0±0.34 65.1±0.57 73.8±0.24 69.2±0.23 60.2±0.84 80.1±0.57 81.1±0.22 60.7±0.74
6h 82.8±0.27 71.2±0.64 73.1±0.66 86.6±0.77 76.08±0.4 51.0±0.35 89.8±0.66 81.3±0.66 73.9±0.33
7h 87.8±0.66 86.8±0.66 86.8±0.36 95.9±0.14 80.9±0.3 69.2±0.67 99.0±0.57 85.2±0.72 76.8±0.44
8h 101.6±0.5 95.7±0.72 88.7±0.57 101.8±0.5 93.5±0.4 87.2±0.57 99.65±0.35 89.2±0.66 85.5±0.37
0 2 4 6 8
0
10
20
30
40
50
60
70
80
90
100
110
P1
P2
P3
P4
P5
P6
P7
P8
P9
Time (Hours)
%Drugrelease

51. Data Analysis of Formulations
Responses X1 X2 TS (%) Rel8h (%) SI5h
RP1 -1 -1 57.26 101.6 1.54
RP2 -1 0 59.23 93.7 1.51
RP3 -1 +1 59.93 87.7 1.53
RP4 0 -1 60.07 101.8 2.49
RP5 0 0 60.26 93.5 2.52
RP6 0 +1 60.81 87.2 2.51
RP7 +1 -1 61.12 99.60 3.54
RP8 +1 0 61.31 89.2 3.42
RP9 +1 +1 62.09 85.5 3.40
Rel8h= +92.98889 -1.45X1 – 7.100X2 – 0.05000X1
2 -1.28333X2
2 + 1.76664X1X2 (R2 =
0.9920)
SI= +2.49444 + 0.96333X1 – 0.021667X2 (R2 = 0.9982)
TS (%) =+60.42+1.35X1+0.73 X2 (R2 = 0.9534)

52. ANOVA Study
Source
Sum of
Squares
Degree of
Freedom
Mean
Square
F Value P Value
Model
Significant/
Not
significant
Model 324.62 5 64.92 74.12 0.0024
Significant
X1 12.61 1 12.61 14.40 0.0321
X2 302.46 1 302.46 345.30 0.0003
X1X2 1.00 1 1.00 0.011 0.9217
(X1)2 3.29 1 3.29 3.76 0.1478
(X2)2 6.24 1 6.24 7.13 0.0757
Residual 2.63 3 0.88 - -
Core Total 327.254 8 - - -
Analysis of variance drug release
Source
Sum of
Squares
Degree of
Freedom
Mean
Square
F Value P Value
Model
Significant/ Not
significant
Model 5.58 5 1.12 713.98 ˂0.0001
Significant
X1 5.57 1 5.57 3564.62 ˂0.0001
X2 2.81 1 2.81 1.80 0.2719
Residual 4.68 3 1.56 - -
Core Total 5.58 8 - - -
Analysis of variance for swelling index at 5h

53. Analysis of variance for tensile strength
Source
Sum of
Squares
Degree of
Freedom
Mean
Square
F Value P Value
Model
Significant/
Not significant
Model 14.13 2 7.07 27.19 0.0010
Significant
X1 10.94 1 10.94 42.07 0.0006
X2 3.20 1 3.20 12.30 0.0127
Residual 1.56 6 0.26 - -
Core Total 15.69 8 - - -

54. Response Surface Plot:
Contour plot Response 3D surface plot

55. Contour plot Response 3D surface plot

56. Contour plot Response 3D surface plot

57. CONCLUSION
The gastroretentive floating bilayer films of rosuvastatin calcium and
propranolol hydrochloride were prepared using immediate and
controlled release polymers by solvent casting method.
Based on the % drug release, swelling index, folding endurance and
floating time formulation RP5 was selected as an optimized
formulation.

58. - Multilayer film DDS
- In-vitro buoyancy by string technique/endoscopy/gamma
scintigraphy
FUTURE PERSPECTIVES

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62. THANK
YOU…