INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIOMEDICAL ANALYSIS | ISSN: 2278 –2664

| JAN-MAR 2014| VOLUME 3 | ISSUE 1 | 14-27

Available Online Through: www.ijprba.com

Research Article
DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL FOR
GASTRORETENTIVE DRUG DELIVERY OF THE NARROW ABSORPTION WINDOW
DRUG ATORVASTATIN CALCIUM
1*, 3 Jayapal Reddy Gangadi, 2Venkateshwar Rao Jupally and 3K.R.S. Sambasiva Rao
1*, 2 Talla Padmavathi College of Pharmacy, Orus, Warangal, 506002, India
1*, 3 Department of Biotechnology, Acharya Nagarjuna University, Guntur, 522510, India
*Corresponding author E-mail: juksanthi2000@gmail.com

ABSTRACT
The present investigation deals with formulation and evaluation of a floating in situ gel of the narrow
absorption window drug Atorvastatin Calcium (ATC). Chitosan-based in-situ gelling systems were
prepared by dissolving various concentrations of chitosan in deionized water, to which varying
concentrations of drug and calcium bicarbonate were added. Fourier transform infrared spectroscopy
(FTIR) and differential scanning calorimetry (DSC) were used to check the presence of any interaction
between the drug and the excipients. The prepared ATC in situ Gel formulations were evaluated for
various properties like viscosity, buoyancy lag time, floating time, swelling index, drug content. The drug
release profiles were fitted into different kinetic models. The floating lag time and floating time of
optimized formulation CF9 were found to be 51 sec and 12 h in dissolution media (0.1N HCl, pH 1.2)
respectively. A decreasing trend in drug release was observed with increasing concentrations of CaCO 3.
The drug release from the in situ gel formulation follows the Zero Order, which indicates Non- Fickian
release. The value of release exponent n for all the formulations (CF1-CF9) ranged from 0.224 to 0.648
and that of optimized formulation (CF9) was 0.514. Floating in situ gel formulation of ATC could be
prepared using floating mechanism to increase the residence time of the drug in stomach and thereby
increase the absorption.

KEY WORDS
In situ gel formulation, Atorvastatin Calcium, CF9, Chitosan, Simple gelation technique.

INTRODUCTION dosing schedule may be inconvenient for the

In the present work, Atorvastatin Calcium patients. Therefore, a long-acting ATC
(ATC) is selective HMG-CoA Reductase formulation is desirable to improve patient
inhibitor widely used in the treatment of compliance. So here an attempt has been
dyslipidemia / Hypercholesterolemia. It is made to sustain the drug release by preparing
considered to be a good candidate for in situ gel formulations of ATC.
reducing dose frequency, for solid oral In sustained release formulation of an oral
sustained release formulation to improve liquid formulation among that floating in situ
patient compliance in Cardiovascular Disease. gel is most beneficial for prolonged gastric
ATC needs to be administered frequently due residence time of drugs in GI tract, which
to its short biological life. However, such a helps to reduce dose frequency, improve

INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIOMEDICAL ANALYSIS | ISSN: 2278 – 2664 |JAN-MAR 2014

www.ijprba.com
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

patient compliance and convenience. The precipitation of the polymer to form gel (e.g.
formation of gels depends on factors like N-Methyl Pyrrolidone).
temperature change, pH change, ionic cross 2. In situ gel Formation Based on Chemical
linking and ultra violet irradiation, from which Changes or Stimuli:
the drug gets released in a sustained manner. Change in the chemical environment of
The oral delivery of drugs having NAW in the system may lead to gel formation by
GI tract with conventional dosage forms due producing polymeric cross linking.
to incomplete drug release and short  Ionic Cross linking:
residence time at absorption site. To (Nagarwal et al., 2009; Rajinikanth et al.,
overcome this drawback and to improve the 2007; Sangeetha et al., 2010)
oral absorption of these drugs, in situ gel is In presence of the various ions present in the
most beneficial. Gel dosage forms are widely body fluids, e.g. Na+, K+, Ca2+, Fe3+ etc., ion
used as drug delivery systems to sustained sensitive polysaccharides, e.g. Carragenan,
drug release. Gellan Gum, Pectin etc., undergo transition in
phase due to development of the polymer
Approaches to produce in situ Gel cross linking, e.g. Sodium alginate undergoes
Different approaches and mechanisms utilized gel formation in presence of Calcium Chloride.
or involved in producing the in situ gel  Enzymatic cross-linking (Rathod et
formation are as follows (Wu et al., 2007). al., 2010)
1. Based on producing physical Enzymes present in the body fluids may also
changes cause cross linking to form a polymer network
2. Based on producing chemical and is considered, as most convenient mode of
changes gel formation. In which such gel forming
3. Based on physiological stimuli system is injected, with microwave radiation,
1. In situ gel Formation by Physical UV radiation or electromagnetic radiation
Changes (Rathod et al., 2010): leads to gel formation within the tissues, e.g. 2,
This approach involves either swelling or 2 dimethoxy-2-phenyl acetophenone,
diffusion phenomenon. In swelling, polymer in ethyleosin etc.
the system absorbs water from the  Photo polymerization (Rathod et al.,
surrounding environment and swells to form 2010; Shah and Jani, 2010)
a viscous gel (e.g. Glycerol MonoOleate). In Exposure of tissues, in which such gel forming
diffusion, solvent in which the drug and system is injected, with microwave radiation,
polymer is dissolved or dispersed, diffuse into UV radiation or electromagnetic radiation
the surrounding tissues causing the leads to gel formation within the tissues, e.g. 2,

15
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

2 Dimethoxy-2-Phenyl acetophenone, Ethyl polymer. Polymer with anionic groups leads

eosin etc. to increase in swelling with increase in the pH,
3. In situ Gel Formation by Physiological while polymer with cationic groups shows a
Stimuli: decrease in the swelling.
Physiological stimuli that can induce gel
formation include change in temperature and Polymers Frequently Used For In Situ
change in pH of the system. Gelling For Gastro Retentive Reasons
 In situ gel formation depending on i) Chitosan (Je and Kim, 2012)
change in temperature (Rathod et Chitosan, the most abundant marine
al., 2010; Shah and Jani, 2010): mucopolysaccharide, is derived from chitin by
In this approach, temperature dependent alkaline deacetylation, and possesses versatile
phase transition from less viscous solution to biological properties such as biocompatibility,
comparatively high viscosity gel is seen. biodegradability, and a non-toxic nature.
Change in temperature causes abrupt change ii) Sodium Alginate (Ganapati et al., 2009;
in the solubility of polymer within system and Nagarwal et al., 2009; Sangeetha et al., 2010):
Polymer-Polymer interaction occurs to form a Sodium alginate is a widely used polymer of
solvated macromolecule of hydrophobic natural origin. Chemically, it is alginic acid
nature. Temperature sensitive polymers are salt, consisting of L-Glucuronic acid and D-
the most studied class for producing the in Mannuronic acid residues connected by 1, 4-
situ gel characteristics, e.g. Polyacrylic acid, Glycosidic linkages. Solution of alginates in
polyacrylamide etc. water form firm gels in presence of di-or
 In situ gel formation due to change trivalent ions (e.g. Calcium and Magnesium
in pH of system (Patel et al., 2010) ions).
Polymers, such as polyacrylic acid and its iii) Pectin (Rathod et al., 2010)
derivative (Carbopol), polymethacrylate etc., iv) Gellan gum (Nagarwal et al, 2009;
undergo gel formation because of change in Rajinikanth et al., 2007; Shah and Jani, 2010):
the pH, due to presence of various ionizable v) Xyloglucan (Rathod et al., 2010)
groups in the chemical structure of the

16
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

FORMULATION: Simple Gelation Technique

To prepare a Heat the polymer

solution at 600C with Then cool the
polymeric solution in
stirring solution at 400C
deionised water

Finally, preservative add Add previously dissolved drug

and stored the solution. solution to polymeric solution.

Figure 1.21: Flow Chart for simple Gelation Technique.

Evaluation of Stomach Specific Floating in  Pilopine HS

situ Gel System:  Akten™
Stomach specific floating in situ gel forming  Virgan
system should be evaluated for following  Cytoryn
parameters: Advantages of in situ forming polymeric
i. Physical appearance (Modasiya et delivery
al., 2010) (Mayavanshi and Gajjar, 2008)
ii. pH of system (Modasiya et al., 2010)  Ease of administration
iii. Viscosity of in situ gelling system  To increase local bioavailability
(Ganapati et al., 2009; Modasiya et al.,  Reduced dose frequency
2010)  Improved patient compliance
iv. In vitro gelation study (Rajinikanth
 Its production is less complex and so
et al., 2007) lowers the investment.
v. Water uptake by gel (Modasiya et
al., 2010) Application of stomach specific floating in
vi. Uniformity of content situ gel
vii. In vitro drug release (Ganapati et (Singh and Kim, 2000; Nayak et al., 2010;
al., 2009; Rajinikanth et al., 2007) Mayavanshi and Gajjar, 2008; Rathod et al,
Marketed Products (Bhimani et al., 2011) 2010; Panwar et al., 2012; Jayswal et al., 2012)
 Liquid Gaviscon  To increased absorption of drugs
 Topalkan which are mainly absorbed from
 Conviron upper part of stomach get prolonged
Commercial Formulations of in situ gel contact time, at their site of maximum
(Shreeraj et al., 2012) absorption. So to increase the extent of
 Timoptic-XE absorption
 Aza Site

17
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

 As the absorption of the drug from solvents and reagents were purchased from
stomach is increased, bioavailability of S.S.Pharma Scientific Equipments, India and
the drug enhanced, remarkably. were of analytical grade.
Increase in the gastric transit time also Methods
causes an increase in the Determination of λmax and preparation of
bioavailability of drug. calibration curve of ATC in 0.1 N HCl
 As drug remains in the stomach till the Preformulation studies were conducted
complete release, frequency of the before starting the formulation of in situ gel
adverse effect on the colon is formulations. This section contains
decreases. determination of λmax, preparation of standard
 Drugs which are absorbed from the graphs of the drug i.e., Atorvastatin Calcium.
stomach get enough residence time for Formulation in situ gel formulations by
absorption rate occurs. Furthermore, simple gelation technique
local action of the drug in prolonged, Chitosan solution was prepared in distilled
so less amount of dose is required. water by heating to 600C under continuous
stirring. After cooling below 40oC. Ingredients
Applicability of in situ gel drug delivery including drug, gelling agent and other
(Sudipta et al, 2004; Nirmal et al., 2010) excipients were weighed accurately, then

 Parenteral Delivery chitosan solutions of different concentrations

 Ocular Delivery were prepared by adding the chitosan to

distilled water containing different
 Rectal Delivery
concentrations of calcium carbonate, and
 Vaginal Delivery
different concentrations of sodium citrate,
 Peroral Delivery
heat the solution to 60○C then cool to below
 Dermal and Transdermal Delivery
40○C and continuous stirring. Appropriate
 Nasal Delivery
amounts of drug and flavoring agent were
then dissolved in the resulting solution and
MATERIALS AND METHODS
formulations were prepared. (Ganapati et al.,
Materials
2009).
Atorvastatin Calcium was a gift from Hetero
Drugs Ltd, Chitosan was obtained from M/s
Nihal Traders Pvt.Ltd, Hyderabad. All other

18
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

Table 1: In situ floating gel formulations with Chitosan (CF1-CF9)

Drug(mg) Excipients (mg)
Formulation
Sodium Calcium D-
Code ATC Chitosan PEO
Citrate Carbonate Sorbitol
CF1 80 250 200 250 250 1000
CF2 80 250 250 250 250 2000
CF3 80 250 300 250 250 3000
CF4 80 500 200 500 500 1000
CF5 80 500 250 500 500 2000
CF6 80 500 300 500 500 3000
CF7 80 1000 200 1000 1000 1000
CF8 80 1000 250 1000 1000 2000
CF9 80 1000 300 1000 1000 3000
Note: Distilled water-Up to 100ml; Methyl paraben & Propyl paraben-0.09%

Evaluation of in situ Floating Gel 1.2 Solution. FLT was found to be 60 sec. TFT
A. Drug polymer interaction study was evaluated to be 12 h result the formation
Compatibility of ATC with gelling agent and of thick gel with good floating tendency
other excipients was established by infrared (Remya et al., 2011).
spectral analysis IR Spectral analysis of E. In vitro gelling capacity
samples (ATC, Chitosan, PEO) was carried out To evaluate the formulations for their in vitro
to investigate the changes in chemical gelling capacity by visual method, solutions of
composition of the drug (Punitha et al, 2010). in situ gel forming drug delivery system were
B. Physical Appearance and pH prepared. The in vitro gelling capacity of
All the prepared chitosan based in situ prepare formulations was measured by
solution was checked for their clarity and the placing 5 ml of the gelation solution (0.1N HCl,
type of the solution. After administration of pH 1.2) in a glass test tube and maintained at
the prepared solution in (0.1N HCl, pH 1.2) 37±1○C temperature. The in vitro gelling
also checked the time required for gel capacity was graded in three categories on the
formation and type of gel formed (Panwar et basis of gelation time and time period for
al., 2012). which they formed gel remains.
C. Viscosity of in situ gelling solutions F. Determination of drug content
The viscosity of formulations was determined 10 ml of the solution was added to 900 ml
by a Brookfield Viscometer DV-III Brookfield, (0.1N HCl, pH 1.2) solution and stirred for 1 h
USA) using cup and bob setting at 50 rpm on a magnetic stirrer. The solution was
(Patel et al., 2010). filtered, suitably diluted with (0.1N HCl, pH
D. Buoyancy lag time (Floating behavior) 1.2) and the drug concentration was
The floating ability of the prepared determined by using a UV-visible
formulations was evaluated in 0.1N HCl, pH

19
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

spectrophotometer at 246 nm against a gel of ATC was monitored up to 3 months at

suitable blank solution. 45ºC temperature and 75% RH periodically
G. Measurement of water uptake by the sample were removed and characterized by
gel (Modasiya et al, 2010) pH, viscosity and drug content (Sarrof et al.,
The water uptake by the gel of all 2012).
formulations can be determined using a Pharmacokinetic and Bioavailability
thermogravimetric analyzer. The in situ gel evaluation of ATC Optimized Formulations
formed in 40 ml of gastric acid buffer (pH 1.2) Comparative Cross-over bioavailability study
was used for this study. From each was conducted on 12 rabbits. The protocol for
formulation the gel portion from the buffer the animal study in prescribed proforma-B
was separated and the excess buffer was was approved by the Institutional Animal
blotted out with a tissue paper. The initial Ethics Committee (IAEC) of Talla Padmavathi
weight of the gel taken was weighed and to College of Pharmacy, Warangal, India, under
this gel 10 ml of distilled water was added and Reg.No.1505/po/a/11 CPCSEA. The optimized
after every 30 minutes of the interval water formulations of ATC were subjected to in vivo
was decanted and the weight of the gel was pharmacokinetic studies. Healthy rabbits of
recorded and the difference in the weight was both sexes weighing 1.5–2.5 kg were fasted
calculated and reported. overnight and divided into two groups (Group
H. In vitro release study I and Group II). Control tablets as reference
Dissolution tests are performed using USP was administered to Group I (n=6). Optimized
dissolution apparatus. Samples are withdrawn formulation (Test) of ATC was given to Group
periodically from the dissolution medium; II (n=6). After 35 days washout period, Group
replenished with the same volume of fresh I received optimized formulations of ATC
medium at sampling time points. Finally (Test) (from Gel) and Group II received
samples were analyzed by U.V control formulation (Reference). Blood
Spectrophotometrically (Preetha et al, 2010). samples were collected and analyzed by
I. Kinetic Analysis of Dissolution Data developed HPLC method for ATC (Khan and
To analyze the in vitro release data various Dehghan, 2011).
kinetic models were used to describe the Various pharmacokinetic parameters such as
release kinetics. Cmax, tmax, AUC, half-life (t1/2), MRT were
J. Stability testing: determined. The determined pharmacokinetic
Preparation of Chitosan based in situ gel of parameters of floating Gel formulations and
ATC was stored in glass container for 1, 2 and control formulations were subjected to
3 month and the stability of the aqueous statistical analysis using paired t-test to
solution of the sodium alginate based in situ determine significance of difference at 0.05

20
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

level of significance. If the value is P<0.05, b) DSC studies

then it was considered as statistically DSC thermogram of ATC (Figure 1-A) showed
significant. one Sharp endothermic peak at 162.60°C and
another broad peak at 247.66°C. Thermogram
RESULTS AND DISCUSSION B chitosan showed broad endothermic peak at
Preformulation Studies 102.29○C and Sharp peak at 312.94○C,
a) FT-IR studies Thermogram C Gel formulation showed Sharp
The FT-IR study was conducted to determine endothermic peak at 71.39oC (Figure 1-A, B
the physicochemical interaction between drug and C).
and polymer. IR spectrum was recorded for
ATC.

Figure 1: Differential Scanning Calorimetry thermograms of A) ATC; B) Chitosan; C) Gel

Formulation.

21
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

Physical Appearance and pH Floating behavior

After administration of the prepared solution The FLT varied with the formulation
in (0.1N HCl, pH 1.2) also checked the time variables. Formulation CF1 exhibited the least
required for gel formation and type of gel FLT (33 sec) while formulation CF9 exhibited
formed (Table 2). the highest FLT (51 sec) (Table 2).
Viscosity of in situ gelling solutions In vitro gelling capacity
This change in viscosity is due to the In vitro gelling capacity of various formulation
proportional increase in the amount of of in situ floating gel is reported in Table 2.
dispersed calcium carbonate. Formulations Determination of drug content
CF1 exhibited the least viscosity values 93 cps, The drug content of all formulations (CF1-
while formulations CF9 showed the highest CF9) varied in between 96.03±0.45% and
viscosity values 265 cps (Table 2). 98.68±0.44% (Table 2).
Table 2: Evaluation data for in situ gel formulations prepared with Chitosan and PEO
(CF1-CF9)
Formulation Viscosity Floating lag time Floating time Drug Content Gelling
pH
code (Cps) (sec) (h) (%)* Capacity
CF1 7.2 93 51 >12 98.03±0.38 ++
CF2 6.9 124 37 >12 98.07±0.35 ++
CF3 7.4 136 33 >12 98.55±0.32 ++
CF4 7.1 142 43 >12 97.06±0.40 +++
CF5 6.9 156 38 >12 96.03±0.45 +++
CF6 7.2 189 29 >12 98.06±0.42 +++
CF7 6.9 192 45 >12 96.08±0.46 +++
CF8 7.1 235 40 >12 97.65±0.40 +++
CF9 7.0 265 33 >12 98.68±0.44 +++
*Mean± SD., (n=3)
Measurement of water uptake by the gel formulation CF4 to CF6 found in range of
The water uptake by gel for formulation CF1 57.39% to 63.81% at the end of 6 h and CF7 to
to CF3 found in range of 59.90% to 64.95% at CF9 found in range of 66.31% to 70.99%
the end of 6 h. The water uptake by gel for (Table 3).
Table 3: Water uptake by gel formulations (CF1-CF9)
Time % of Water uptake by gel
(min) CF1 CF2 CF3 CF4 CF5 CF6 CF7 CF8 CF9
30 3.66 6.05 8.55 5.16 8.23 11.26 8.44 3.76 7.24
60 8.50 11.55 12.79 9.70 13.69 16.46 14.23 6.44 10.67
90 14.05 16.22 18.30 15.07 18.89 21.78 22.79 10.11 20.91
120 19.12 21.88 23.60 19.88 23.34 26.54 28.67 14.81 25.55
150 24.55 27.25 29.58 26.11 28.89 31.06 32.16 20.10 29.49
180 29.28 30.40 32.66 30.76 32.46 36.87 38.97 25.33 34.64
210 34.50 36.78 38.73 36.70 37.83 42.62 43.22 30.13 39.21
240 39.44 40.63 42.60 40.21 41.36 46.12 48.32 35.30 43.66
270 43.40 45.94 47.83 44.30 47.76 50.78 52.99 40.32 48.77
300 47.60 49.98 51.04 49.84 51.29 55.36 56.22 45.33 54.45
330 52.90 55.67 57.11 54.58 57.88 59.91 60.33 51.67 59.89
360 59.90 61.80 64.95 57.39 62.63 63.81 66.31 55.99 70.99

22
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

120 CF1

% Cumulative Drug Release

CF2
100
CF3
80 CF4
CF5
60
CF6
40 CF7
CF8
20
CF9
0
0 2 4 6 8 10 12 14

Time (h)

Figure 3: In vitro Release Profile of ATC in situ gel formulations (CF1-CF9).

In vitro release study All the formulations (CF1-CF9) followed the
From the in vitro drug release data it was zero order kinetics and R2 values were ranged
found that the drug release from the from 0.972 to 0.996. The value of release
formulations containing Chitosan and PEO, exponent n for all the formulations (CF1-CF9)
CF1-CF9, was found to be within the range of ranged from 0.224 to 0.648 (Table 4 and
76.09±0.89% to 94.43±0.90% (Figure 3). Figure 4).
Kinetic Analysis of Dissolution Data
Table 4: Model fitting of the release profile using four different models
Zero First Higuchi Korsmeyer-
Formulation
order order kinetics Peppas
Code
(r2) (r2) (r2) (r2) n
CF1 0.989 0.927 0922 0.911 0.224
CF2 0.977 0.923 0.870 0.917 0.225
CF3 0.975 0.797 0.869 0.778 0.272
CF4 0.972 0.885 0.853 0.929 0.413
CF5 0.972 0.988 0.945 0.895 0.445
CF6 0.986 0.907 0.902 0.790 0.648
CF7 0.996 0.950 0.912 0.888 0.505
CF8 0.984 0.735 0.888 0.864 0.549
CF9 0.984 0.947 0.888 0.869 0.514

23
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

zero order y = 7.0534x - 2.4193 First order

log percent remaining

y = -0.0584x + 2.077
R² = 0.9847

cumulative % release
R² = 0.9475
100 2.500
80 2.000
60 1.500
40 1.000
20 0.500
0 0.000
0 5 10 15
-20 0 5 10 15
Time (h) Time (h)

Higuchi y = 25.88x - 18.327 Korsemeyer pepasy = 1.3477x + 0.5142

R² = 0.8881 R² = 0.8698
100 2.5

Log % release
cumlative % release

2
50 1.5
1
0 0.5
0 1 2 3 4 0
0 0.5 1 1.5
-50 Sq root t Log t

Figure 4: Release kinetics of optimized formulation (CF9)

Stability Studies humidity chamber maintained 40 ± 2 °C / 75 ±

The optimized formulation (CF9 and SF9) 5 % RH for 3 months (Table 5).
sealed in vial with rubber cap and kept in
Table 5: Stability studies of optimized formulation CF9
Time period for Drug content Drug release
pH Viscosity (cps)
sampling (%) (%)
Initial 7.10 265 98.64 76.09
After 1 month 7.10 265 98.62 76.89
After 2nd month 7.13 269 98.50 77.22
After 3rd month 7.16 269 98.00 77.21

Pharmacokinetic evaluation in rabbits The pharmacokinetic parameters were

In this design, pharmacokinetic evaluation calculated using Kinetica software. The
was done on Optimized formulations in following Table 6 contained the obtained data.
comparison to control formulation of ATC.

24
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

Table 6: Pharmacokinetic parameters of Atorvastatin Calcium control formulation

(Lipitor) and in situ floating gel formulation (CF9) in Rabbits. (n=12).

Pharmacokinetic Parameters Control tablets CF9

Cmax (ng/ml) 503.98±87.50 882.15±39.7338
Tmax (h) 2±0.65 1.5±0.0
AUC0-t (ng.h/ml) 2615.79±827.054 4434.04±278.264
AUC0-α (ng.h/ml) 3062.21±450 5497.009±678.258
t1/2 (h) 3.99±0.61991 5.08±0.87825
MRT (h) 6.68±0.77745 7.4±1.1694
%Fr 100 169.51
By student paired t-test, p<0.05 is considered statistically significant in all the parameters.

1000
Control
Plasma Drug Concentration

800 Gel formulation CF9

600
(ng/ml)

400

200

0
0 2 4 6 8 10 12 14
-200 Time (h)
Figure 5: Mean serum concentration-time profiles of control formulation and in situ
Floating Gel formulation (CF9) in rabbits (n=12).

The mean (± SD) ATC serum concentration- ng×h/ml, respectively. Mean residence time
time curves for test (CF9) and reference (MRT) values for reference and test
(conventional formulation) are shown in the formulation were 6.68±0.77h and 7.4±1.16 h,
Figure 5. The Cmax value for reference respectively. In the present study student’s
formulation was found to be 503.98±87.50 paired t-test showed that there was significant
ng/ml, where as Cmax value for test (CF9) was difference (p<0.05) between two formulations
found to be 882.15±39.7338 ng/ml. Tmax in their pharmacokinetic parameters, AUC0-∞,
values for both reference and test (CF9) was Cmax, Tmax, and MRT. The increased Relative
found to be 2±0.65 h and 1.5±0.0h bioavailability of test formulation was 1.69
respectively. t1/2 value for reference was found fold when compared to reference formulation.
to be 3.99±0.61h and for test 5.08±0.87h. (Table 6)
AUC0-∞ values for reference and test were
3062.21±450ng×h/ml and 5497.009±678.258 REFERENCES

25
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

Bhimani RD, Patel JK and Patel VP, 2011, characterizations, E-J.Sci.Tech., 5(1),
Development and evaluation floating in pp.27-42.
situ gel of clarithromycin, Int.J.Pharm Modasiya MK, Prajapati BG, Patel VM, Patel JK,
Res., 3, pp.32-35. 2010, Sodium alginate based in situ
Furquan Nazimuddin Khan and Mohamed Hassan gelling system of famotidine:
G. Dehghan, 2011, Enhanced preparation and in vivo
Bioavailability of Atorvastatin Calcium characterizations, E-J.Sci.Tech., 5(1),
from Stabilized Gastric Resident pp.27-42.
Formulation, AAPS.Pharm.Sci.Tech., 12 Nagarwal RC, Srinatha A and Pandit JK, 2009, In
(4), pp.1077-1086. situ forming formulation: development,
Ganapati R, Bhimagoni SK, Anegundha S, 2009, evaluation and optimization using 32
Floating drug delivery of a locally factorial design, AAPS.Pharm.Sci.Tech.,
acting H2-antagonist: An Approach 10 (3), pp.977-984.
using an in situ gelling liquid Nirmal HB, Bakliwal SR and Pawar SP, 2010, In situ
formulation, Acta.Pharm., 59, 345–354. gel: New trends in Controlled and
Jayswal BD, Yadav VT, Patel KN, Patel BA, Patel PA, Sustained Drug Delivery System,
2012, Formulation and Evaluation of Int.J.Pharm.Tech.Res., 2(2), pp.1398-
floating in situ gel based 1408.
gastroretentive drug delivery of Panwar AS and Manoj Sharma, 2012, In situ oral
cimetidine, Int.J.Pharm.Res.Sch., 1, 327- gel advancement in pud: a review,
337. Int.J.Pharm.Med.Sci., 2, pp.51-78.
Je JY and Kim S, 2012, Chitosan as potential marine Preetha PJ, Karthika K, Rekha NR and Elshafie K,
nutraceutical, Adv.Food.Nutr Res., 65, 2010, Formulation and evaluation of in
pp.121-135 situ ophthalmic gels of Diclofenac
Kunal P Nayak, Pratik Upadhyay, Jayant Deshpande Sodium, J.Chem.Pharm.Res., 2(3),
Arohi R. Valera, Nirav P Chauhan, 2012, pp.528-535.
Gastroretentive drug delivery system Punitha K, Khadhir S, Ravichandiran V, Umadevi
and recent approach: A Review, SK, Vaijayanathi V, Padmapriya S and
J.Pharm.Res.Opi., 2 (1), pp.1-8. Kumar SS, 2010, Intragastric floating
Mayavanshi AV and Gajjar SS, 2008, Floating drug drug delivery system of Ranitidine
delivery systems to increase gastric Hydrochloride, Int.J.Pharma.Pharm.Sci.,
retention of drugs, A Review. 2 (4), pp.105-108.
Res.J.Pharm.Tech., 4, pp.346-348. Rajinikanth PS, Balasubramaniam J and Mishra B,
Modasiya MK, Prajapati BG, Patel VM, Patel JK, 2007. Development and evaluation of a
2010, Sodium alginate based in situ novel floating in situ gelling system of
gelling system of famotidine: amoxicillin for eradication of Helico
preparation and in vivo bacterpylori, Int.J.Pharma., 335,
pp.114-122.

26
 Jayapal Reddy Gangadi* et al: DESIGN AND EVALUATION OF A NOVEL FLOATING IN SITU GEL………..

Rathod H, Patel V and Modasia M, 2010, In situ gel Shah DP and Jani GK, 2010, A newer application of
as a novel approach of gastroretentive physically modified gellan gum in
drug delivery, Int.J.Pharm.Life Sci., tablet formulation using factorial
1(8), pp.440-447. design, ARS.Pharmaceutica., 51 (1),
Remya PN, Damodharan N and Venkata MA, 2011, pp.28-40.
Oral Sustained Delivery of Ranitidine Shreeraj Shah, Pratik Upadhyay, Darsh Parikh, Jinal
from in situ gelling sodium alginate Shah, 2012, in situ Gel: A Novel
formulation, J.Chem. Pharm.Res., 3(3), Approach of gastro retentive Drug
pp. 814-821. Delivery, Asian J.Biomed. Pharm. Sci., 2,
Sangeetha, S, Harish G, Medapati R, Gantasala P, pp.01-08.
Raju B and Damodharan N, 2010, Oral Singh BN and Kim KH. 2000, Floating drug delivery
sustained delivery of salbutamol systems: an approach to oral controlled
using in situ gelation of sodium drug delivery via gastric retention,
alginate, Int.J.Curr.Pharma.Res., 2 (3), J.Control.Rel., 63 (3), pp.235-259.
61-64. Sudipta Ganguly and Alekha Dash K, 2004, A novel
Sarrof R, Shaikh A, Pawar Y and Kumbhar S, 2012, in situ gel for sustained drug delivery
Sodium Alginate Based Oral in situ and targeting, Int.J.Pharmaceutics., 2,
Floating Gel of Metformin pp.83-92.
Hydrochloride, Res.J.Pharm.Biol.Chem.
Sci., 3(1), pp.890-897.

27