slideshae on research work

1. FORMULATION AND EVALUATION OF ORAL
FLOATABLE INSITU GEL USING
BIODEGRADABLE POLYMERS
Presented by:
Miss. Pallavi Padwal
Guided by:
Mr. V.A. Arsul
Professor
Shri Bhagwan College of Pharmacy, Aurangabad 1

2. CONTENTS
1. Introduction
2. Need and Objectives
3. Review of Literature
4. Plan of Work
5. Drug and Polymers Profile
6. Experimental Work
7. Material and Equipments
8. Results and Discussion
9. Summary and Conclusion
10. References 2

3. Introduction
3
Gels :
Gels are semisolid systems containing both solid and liquid components.. The
liquid phase of the gel may be retained within a three-dimensional polymer matrix.
Drugs can be suspended in the matrix or dissolved in the liquid phase.
In- Situ gel drug delivery system :
In-situ is a Latin word which means ‘In its original place or in position’. In this
type of drug delivery system, the preparation is in a solution form before
administration in body ,but it converts into a gel form after administration.

4. Oral insitu gel drug delivery system:
 Administration route for in situ gel are oral, ocular, rectal, vaginal,
injectable and intra peritoneal routes.
 Ease of administration and reduced frequency of administration, improved
patient compliance and comfort.
 Deliverance of accurate dose, in situ gel formation occurs due to one or
combination of different stimuli like pH change, temperature modulation
and solvent exchange.
 Smart polymeric systems represent promising means of delivering
the drugs. These polymers undergo sol-gel transition, once
administered.
4

5. INTRODUCTION
 Oral ingestion is the most convenient & commonly used route of
drug delivery.
 Recently more than 40% NCEs (new chemical entities)
developed in pharmaceutical industry are practically insoluble in
water.
 Dissolution enhancement of poorly water soluble drugs
represents big issue in pharmaceutical research.
 The present study deals with the bioavailability enhancement of
drug that belongs to the class II of Biopharmaceutical
classification system (BCS) by using microwaves.
5

6. INTRODUCTION
6
 Floating drug delivery system:
 Floating drug delivery systems (FDDS) or hydro dynamically controlled
systems are low-density systems that have sufficient buoyancy to float
over the gastric contents and 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.
 This results in an increased Gastric retention time and a better
control of the fluctuations in plasma drug concentration.
 Gastroretentive systems can remain in the gastric region for
several hours and hence significantly prolong the gastric residence
time of drug.

7. INTRODUCTION
Prolonged gastric retention of drug is required in the following conditions:
 Drug is best absorbed from stomach e.g. aspirin, phenylbutazone etc.
 Gastric fluids facilitate and improve the disintegration and dissolution of the
drug.
 Dissolution and absorption of drug is promoted by the food e.g. griseoflvin.
 Slow dissolving drugs.
 Drug show local effect within stomach.
7

8. INTRODUCTION
 DISADVANTAGES OF GASTRO RETENTIVE DRUG
DELIVERY SYSTEM:
 Floating system is not feasible for those drugs that have
solubility or stability problem in G.I. tract.
 These systems require a high level of fluid in the stomach for
drug delivery to float and work efficiently-coat, water.
 The drugs that are significantly absorbed through out
gastrointestinal tract, which undergo significant first pass
metabolism, are only desirable candidate.
 Some drugs present in the floating system causes irritation to
gastric mucosa.
8

9. NEED AND OBJECTIVE
1.Pre-formulation studies of Atenolol.
2. To develop an ideal oral in-situ polymeric drug delivery system by using
factorial design (Design expert software). 3. Optimization of formulation.
4. Evaluation of oral in-situ gel for their physicochemical studies (Viscosity,
Clarity, Strength, Gelling capacity, Gellation PH and temperature, In-vitro
studies) and
5. Stability studies for select
9

10. REVIEW OF LITERATURE
Kubo W.et al(2003), worked on oral administration of aqueous solutions of either
gellan gum (1.0 %, w/v) or sodium alginate (1.5 %, w/v) containing calcium ions
in complexed form resulted in the formation of gel depots in rabbit and rat
stomachs as a consequence of the release of the calcium ions in the acidic
environment. In vitro release studies showed diffusion controlled release and also
the bioavailability was found to be similar like that of a commercial marketed
suspension.
Miyazaki S. et al(2003),has prepared Insitu gelling system for paracetamol was
prepared to enhance its bioavailability. According to the study the potential of
xyloglucan formulation with in situ gelling properties for oral sustained delivery
of paracetamol was evaluated. Gelation of dilute aqueous solutions in rabbits and
rats stomach was seen after in vitro release studies and also bioavailability was
similar to that of a commercially available suspension.
Attwood D.et al(2001),prepared three different liquid formulations containing
cimetidine were used like (a) enzyme-degraded xyloglucan, (b) gellan gum and;
(c) sodium alginate has been assessed for their potential for the in situ gelling
properties of oral delivery of cimetidine. The in vitro release of cimetidine from
gels followed root-time kinetics over a period of six hours.
10

11. Plasma levels of cimetidine of each of the formulations were compared with those
resulting from administration of a commercial cimetidine/alginate suspension with
an identical drug loading.
Jaimini M.et al(2007),has formulated gastro retentive drug delivery system of
famotidine. Floating tablets of famotidine were prepared employing two different
grades of methocel K100 and methocel K15M by effervescent technique; these
grades of methocel were evaluated for their gel forming properties. Sodium
bicarbonate was incorporated as a gas-generating agent. Floating tablets were
evaluated for uniformity of weight, hardness, friability, drug content, in vitro
buoyancy and dissolution studies. Effect of citric acid on drug release profile &
floating properties was investigated.
Ramesh C.et al (2009),has developed and evaluated the in-situ gel formulation by using
33 factorial design to retain in the stomach for extended period of time based on the
three independent factors: concentrations of like gellan gum(x1), sodium
alginate(x2) and anti-diabetic drug metformin(x3) and also considered five
dependent variables are release exponents(Y1), dissolution efficiency(Y2), drug
release at 30min(Y3), drug release at 210min(Y4), drug release at 480min(Y5).
Three dimensional surface response plots were drawn to evaluate the interaction of
independent variables on the chosen dependent variables. Three factorial levels
coded for low, medium, and high settings (−1, 0 and +1, respectively) were
considered for three independent variables.
11

12. Literature survey
Procurement of drug
and polymers
Characterization of
drug and polymers
Analytical method
development
Formulation of insitu gel of
Atenolol
Evaluation of insitu gel
of Atenolol
Conclusion
12

13. DRUG PROFILE Mol. Formula C14H22N3O3
Mol. Weight 236.27
Appearance white or Almost
white crystalline
powder
Category Antihypertensive
Dosage form Tablet
Half life 6-7 hours
Log P 0.5
Melting point 152-155 0C
Solubility Poorly soluble in
water, solubility
increases with
addition of ethanol
Atenolol
13

14. POLYMER PROFILE
Guar gum:
 The most important property of guar gum is its ability to
hydrate rapidly in cold water to attain uniform and very high
viscosity at relatively low concentrations. Apart from being
themost cost-effective stabilizer and emulsifier it provides
texture improvement and water binding, enhances mouth feel
and controls crystal formation. The main properties of guar
gum are:
 It is soluble in hot & cold water but insoluble in most organic
solvents.
 It has strong hydrogen bonding properties.
 It has excellent thickening, emulsion, stabilizing and film
forming properties.
 It has excellent ability to control rheology by water phase
management.
 The viscosity of guar gum is influenced by temperature, pH,
presence of salts andother solids.
14

15. Sodium Algenate:
 Sodium alginate is a widely used polymer of natural
origin. Chemically, it is alginic acid salt, consisting of –
L-glucuronic acid and -D-mannuronic acid residues
connected by 1,4-glycosidic linkages. Solution of
alginates in water form firm gels in presence of di-or
trivalent ions (e.g. calcium and magnesium ions).
Alginates salts, specifically, sodium alginate is mostly
used for preparation of gel forming solution, for
delivery of the drugs and proteins. Alginate salts are
considered most favourable because of biodegradable
and non toxic nature, with additional bio- adhesive
property.
15

16. MATERIAL AND EQUIPMENTS
Sr. No. Name of Material Name of Supplier
1 Atenolol Ipca pharmaceuticals ltd
Aurangabad
2 Sodium Algenate Snap natural & Algenate products
Pvt. Ltd. Tamilnadu
3 Guar gum Biochemical healthcare Mumbai
4 Calcium carbonate S.D Fine Chemicals
5 Methyl paraben S.D Fine Chemicals
6 Propyl paraben S.D Fine Chemicals
16

17. Sr. No. Name of Instrument Name of Company
1 UV-Visible
spectrophotometer
SHIMADZU UV-1800, Japan.
2 IR Spectrophotometer SHIMADZU, Japan.
3 Dissolution Apparatus Electrolab TDT- 08L, Mumbai.
4 Magnetic Stirrer REMI 1ML instruments, Mumbai.
5 Electornic Balance The Bobbay Burmah Trading
6 Brookfield Viscometer Model DV 11 PRO
7 Stability Chamber Thermolab India
8 pH Meter Equiptronic EQ-610.
17

18. Preparation of insitu gelling solutions
18
Subject to stirring using electronic Stirrer for definite
period of time until dispersion was uniformly formed
Cooled to below 400c
Atenolol and colcium carbonate was added
Guar gum and preservarive was dispersed in
deionised water preheared to 900c with stirring. To
this Sodium Algenate was added.

19. EXPERIMENTAL WORK
Characterization of drug:
1. Melting point Analysis
2. Spectrophotometric characterization
a) Determination of λmax
b) Preparation of calibration curve
3. Solubility studies
Excess of drug was added to 10ml distilled water and kept for
48 hrs on magnetic stirrer (1ML). Sample was filtered, diluted and
analyzed by UV Spectrophotometer.
4. Infrared Spectrophotometric analysis
-identification of drug
-400 to 4000cm-1
19

20. Evaluation of bionanocomposite powder
Solubility study:
Saturated drug solutions were prepared in different solvents in
deionised water,0.1N hydrochloric acid and agitated on Rotary shaker
for 24hour. The samples were analyzed by double beam UV
Spectrophotometer at 225 nm(Japan, Jasco V-530).
Melting point determination:
The melting point of the given drug sample was determined using
Method I specified in the Indian Pharmacopoeia 2007 (2.4.21) using
the liquid paraffin as a bath liquid by Digital Melting Point apparatus.
The melting point was noted and the readings were taken in
triplicate44.
20

21. FTIR
IR spectra forAtenolo and the excipients were recorded in a
Fourier transform infrared (FTIR) spectrophotometer (FTIR-8400
S, Shimadzu, Japan) with KBr pellets. The scanning range was
400– 4000 cm−1. .
DSC
using DSC (Diamond DSC, Perkin Elmer) at heating rate of
5oC/min from temperature 0-400oC.
.
21

22. Preparation of Insitu gel
22
Ingredients(5%
w/v)
Formulation code
F1 F2 F3 F4 F5 F6 F7 F8 F9
Atenolol 0.5% 0.5% 0.5
%
0.5
%
0.5% 0.5% 0.5% 0.5% 0.5
%
Sodium Algenate 0.4% 0.6% 0.8
%
0.4
%
0.6% 0.8% 0.4% 0.6% 0.8
%
Guar gum 0.5% 0.5% 0.5
%
1% 1% 1% 1.5% 1.5% 1.5
%
Calcium
carbonate
2% 2% 2% 2% 2% 2% 2% 2% 2%
Methyl paraben 0.020%
Propyl paraben 0.180%
Total volume 100ml

23. Evaluation of immediate release tablet
 Precompression evaluation
Precompression evaluation including angle of repose,
Carr’s index, Hausner’s ratio of tablet mixture were performed as
according to USP 30 (2007).
 Post compression evaluation
Hardness, weight variation, friability, disintegration time,
drug content evaluation were performed by following USP 30
(2007).
23

24.  Stability study
Stability study of optimized tablets was performed as according to
international conference on hormonisation (ICH) guidelines at 40 ± 20C and 75
± 5% relative humidity for three months. Sample were removed and analyzed
for disintegration time, % drug content and in-vitro drug release at 0, 30, 60
and 90 days.
24

25. RESULTS AND DISCUSSION
Characterization of drug:
1. Melting point analysis
Melting point of pure drug was found to be 1910C.
2. Spectrophotometric characterization
a) Determination of λmax
25

26. b) Calibration curve of Carbamazepine in distilled water
-obtained coefficient value of 0.997
26
Sr.
No.
Conc.
(µg/ml)
Absorban
ce
1 0 0.000
2 4 0.203
3 8 0.361
4 12 0.536
5 16 0.755
6 20 0.892
3. Solubility studies
Solubility of pure drug was found to be 0.156 ± 0.043 mg/ml.
Data for calibration curve of Carbamazepine
in dist. water
Standard calibration curve of Carbamazepine in
dist. water

27. Characterization of polymers
27
Sr.
No.
Material %Swelling Viscosity
(cps)
Foaming
index
1. Acacia 72.62 ± 1.32 4.23 ± 0.112 18.33 ± 0.922
2. Ghatti gum 75.53 ± 2.10 6.12 ± 0.181 16.63 ± 0.745
Data are means ± SD, n = 3

28. 28
Drug-polymer
Ratio
Physical mixture Bionanocomposites
CBZGGP
(mg/ml)
CBZACP
(mg/ml)
CBZGGB
(mg/ml)
CBZACB
(mg/ml)
1:1 1.17 ± 0.251 2.13 ± 0.361 2.89 ± 0.326 4.62 ± 0.745
1:2 1.64 ± 0.362 2.86 ± 0.425 3.57 ± .233 5.74 ± 0.682
1:3 2.48 ± 0.634 3.36 ± 0.254 4.22 ± 0.421 6.62 ± 0.658
Solubility results of Physical mixtures and Bionanocomposites
Data are means ± SD, n = 3

29. Drug content analysis of bionanocomposites
29
Bionanocomposites CBZGGBNC CBZACBNC
Drug incorporated 97% 99%
In-vitro dissolution test of bionanocomposite powder
Data for calibration curve of Carbamazepine
in 1% SLS
Sr.
No.
Conc.
(µg/ml)
Absorbance
1 0 0.000
2 4 0.236
3 8 0.417
4 12 0.623
5 16 0.844
6 20 1.038
Standard calibration curve of Carbamazepine in
1% SLS

30. In-vitro dissolution of pure CBZ, CBZACBNC and CBZGGBNC
30
Percent Drug Release
Sr. No. Time (Min) Pure CBZ CBZACBNC CBZGGBNC
1 5 4.25 ± 0.269 16.84 ± 0.158 11.26 ± 0.124
2 10 10.44 ± 0.432 31.23 ± 0.365 23.56 ± 0.457
3 15 15.62 ± 0.942 42.15 ± 1.069 31.54 ± 1.254
4 30 24.65 ± 1.684 62.94 ± 2.584 54.28 ± 2.687
5 45 33.58 ± 2.636 77.68 ± 3.405 72.14 ± 2.960
6 60 39.15 ± 2.113 90.34 ± 3.267 83.29 ± 3.341

31. 31
FT-IR Studies
Principle Peaks of Pure CBZ, CBZACBNC and CBZGGBNC

32. 32
Principle Peaks of Pure CBZ, CBZACBNC and CBZGGBNC
32
FT-IR Studies
Sr.
No.
Functional
group
Standard
IR ranges
IR ranges obtained
Pure KE KEACNBC KEGGNBC
1 NH stretching
of NH2
Near 3450
and 3180
3466.08 3466.08 3466.08
2 Aromatic CH
stretching
3010-3090 3157.47 3159.40 3157.47
3 C=O stretching
of CONH2
1638-1680 1678.14 1678.07 1681.93
4 C=C ring
stretching
At 1600 and
1475
1604.77,
1489.05
1604.77,
1489.05
1606.70,
1487.12
-Principle peak values of drug remained unchanged in
the microwave treated BNCs

33. DSC
33
-Drug showed a small and sharp characteristic endothermic peak at 193.49
0C whereas DSC thermograms of CBZACBNC and CBZGGBNC showed
endothermic peak at 192.67 0C and 174.12 0C respectively.
-There was no considerable change in the DSC thermogram values when
CBZ was mixed with excipients compared to that of pure CBZ.

34. XRD
34
XRD patterns of pure CBZ, CBZACBNC and CBZGGBNC

35. Intense peak and 2θ value of CBZ, CBZACBNC and CBZGGBNC
35
2θ Value
Intensity count (cps)
Pure CBZ CBZACBNC CBZGGBNC
13.645 2064 305 156
15.829 3034 254 243
25.444 2608 353 303
27.957 5829 410 604
• Carbamazepine showed numerous sharp peaks between
13.64 to 27.95 at 2θ, which are the characteristic of a
crystalline compound.
• CBZACBNC and CBZGGBNC showed the presence of less
intense peaks as compared to pure drug between13.64 to
27.95, at 2θ which suggested that the drug was of a high
crystalline nature.
XRD

36. SEM
36

37. SEM
 Pure drug particles were found to be tabular in shape with
smooth surface, while optimized BNCs were found to be
irregular in shape and size with rough surface.
 The SEM images of pure drug particles and optimized BNCs
clearly indicated that the crystal shape of Carbamazepine was
completely changed in CBZACBNC showing embedded
Carbamazepine crystals in the acacia matrix.
37

38. 38
Size distribution analysis
• The average particle size of optimized BNCs was found to be 379.5
nm

39. Evaluation of immediate release tablet
Pre compression evaluation
39
Formulation
code
Angle of repose
(θ)
Carr’s index
(%)
Hausner’s
ratio
F1 22.26 ± 1.653 10.56 ± 0.961 1.322 ± 0.026
F2 20.56 ± 1.681 11.64 ± 0.674 1.062 ± 0.069
F3 23.11 ± 1.388 13.76 ± 0.766 0.968 ± 0.156
F4 19.52 ± 0.968 13.17 ± 0.221 1.236 ± .0325
 Prepared formulation mixture has excellent flow
properties, good compressibility which allows these
formulation mixtures to be directly compressed into
tablet.

40. Post Compression Evaluation
40
Batch
Weight variation
(mg)
Hardness
(kg/cm2)
Friability
(%)
Drug content
uniformity (%)
Disintegration
time (Sec)
F1 507 ± 4.621 3.44 ± 0.125 0.48 ± 0.082 98 51 ± 1.269
F2 513 ± 3.625 4.65 ± 0.168 0.41 ± 0.063 94 66 ± 2.365
F3 496 ± 3.591 4.96 ± 0.215 0.38 ± 0.051 97 48 ± 1.874
F4 504 ± 3.584 3.84 ± 0.325 0.45 ± 0.026 99 41 ± 2.315
 All the parameters are within the limits given in the USP
XXX (2007).
 Formulation F4 show best disintegration time.

41. In-vitro drug release study
41
Percent Drug Release
Sr. No. Time (Min) Formulation (F4)
1 5 17.35 ± 0.235
2 10 32.65 ± 0.362
3 15 43.20 ± 1.253
4 30 62.32 ± 2.321
5 45 78.84 ± 3.587
6 60 91.42 ± 2.698
Dissolution comparison of pure CBZ versus optimized formulation

42. Stability studies
42
Time (days) Disintegration
time (sec)
% drug
content
% In-vitro drug
release
0 41 ± 0.245 99 91.42 ± 2.698
30 59 ± 0.351 97 89.74 ± 2.981
60 49 ± 0.154 98 89.17 ± 3.422
90 61 ± 0.221 98 90.35 ± 3.473
 Prepared formulation is stable and not much affected by
elevated temperature and humidity condition.

43. CONCLUSIONS
 Above studies successfully demonstrated the use of natural
polymers such as acacia and ghatti gum as carrier for
formation of microwave generated BNCs
 Solubility and dissolution studies confirm the use of these
materials for solubility enhancement.
 Finally from overall results it can be concluded that
microwave generated BNCs can be successfully used for the
solubility, dissolution and ultimately bioavailability
enhancement of drug.
43

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