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Research Paper

Formulation and Evaluation of in situ Gels Containing

Clotrimazole for Oral Candidiasis
N. M. HARISH*, P. PRABHU, R. N. CHARYULU, M. A. GULZAR AND E. V. S. SUBRAHMANYAM
NGSM Institute of Pharmaceutical Sciences, Paneer, Deralakatte Post, Mangalore-574 160, India

Harish, et al.: In situ Gels of Clotrimazole for Oral Candidiasis

Gel dosage forms are successfully used as drug delivery systems to control drug release and protect the medicaments
from a hostile environment. The main objective is to formulate and evaluate in situ oral topical gels of clotrimazole
based on the concept of pH triggered and ion activated systems. The system utilizes polymers that exhibit sol-
to-gel phase transition due to change in specific physico-chemical parameters. A pH triggered system consisting
of carbopol 934P (0.2-1.4% w/v) and ion triggered system using gellan gum (0.1-0.75% w/v) along with
hydroxylpropylmethylcelluose E50LV was used to prolong the release of clotrimazole (0.1% w/v). Formulations were
evaluated for gelling capacity, viscosity, gel strength, bioadhesive force, spreadability, microbiological studies and
in vitro release. The use of carbopol as in situ gel forming system was substantiated by the property to transform
into stiff gels when the pH was raised, whereas in gellan gum this transformation occurred in the presence of
monovalent/divalent cations. Effect of calcium carbonate and other process parameters optimized and found that
increase in calcium ions produced stronger gels. The drug content, clarity, and pH of the formulation were found
to be satisfactory. The viscosity was found to be in the range 5 to 85 centipoise for the sol, whereas for the gels
it was up to 16000 centipoise. The formulation showed pseudoplastic flow with thixotrophy. The maximum gel
strength (using texture analyzer) and bioadhesion was found to be up to 6.5 g and 4 g, respectively. The optimized
formulations were able to release the drug up to 6 h. The formulation containing gellan gum showed better sustained
release compared to carbopol based gels.

Key words: Mucoadhesive in situ gels, prolonged release, carbopol, gellan gum, hydroxypropylmethylcellulose,
clotrimazole

Oral candidiasis is one of the most common longer duration of time. Therefore some researchers
pathological conditions affecting the oral mucosa. had prepared and reported new formulation such as
Local delivery of drugs to the tissues of the oral gels, mucoadhesive tablets, pH sensitive excipients
cavity has a number of applications including composition mucoadhesive microspheres, which were
the treatment of toothache, periodontal diseases, able to reside in oral cavity for an extended period
dental caries, bacterial and fungal infections. The for more effective candidiasis eradication [3,4]. As
conventional formulations for the local delivery of conventional drug delivery system does not remain in
drugs to the oral cavity are the mouth paints, rinses, the oral cavity for prolonged period, they are unable
troches, creams and suspensions[1,2]. The reason for to deliver the antifungal agents to the site of infection
incomplete eradication of candidiasis in most cases in effective concentrations and in fully active forms.
may be due to the short residence time of antifungal Hence attention has been focused on extended release
agents in the oral cavity. The other reason may be topical antifungal formulations for prolonging active
degradation of antifungal agents in salivary fluid. drug concentrations in the oral cavity. Jung et al.[3]
One way to improve the efficacy in eradicating the developed mucoadhesive thermo-sensitive gels and
infection is to deliver the antifungal locally in the found that in vivo antifungal activity of clotrimazole
oral cavity. Better stability and longer residence time (CT) was significantly prolonged. Ning et al. [4]
will allow more of the antifungal to penetrate through formulated CT containing vaginal proliposomes, which
the oral mucous layer to act on Candida species for showed prolonged drug release and may increase
amount of drug retention into the mucosa to result in
*Address for correspondence more antifungal efficacy. Using suitable carriers which
E-mail: harishnayari@gmail.com can effectively administer the drug for an extended
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period of time not only reduces the systemic side was determined using a calibrated pH meter (Elico,
effects but also improves the therapeutic efficacy and Hyderabad, India). The values were taken as average
patient compliance. of 3 reading.

The aim of the present work was to develop pH Determination of mucoadhesive force:
triggered system using carbopol and ion triggered The mucoadhesive force of in situ gels on tissue
using gellan gum, in situ gels for local release specimen (cheek of chicken) was determined by
of CT, in the buccal cavity for the treatment of means of mucoadhesive force measuring apparatus,
oropharyngeal candidiasis. A combination of carbopol fabricated in our laboratory. The pieces of tissue
- hydroxypropylmethylcellulose (HPMC) and gellan were stored frozen in phosphate buffer at pH 7.4,
gum-HPMC were investigated as vehicle for the and thawed to the room temperature before use. At
formulation. the time of testing, a section of tissue was secured
(keeping the mucosal side out) to the upper side
MATERIALS AND METHODS of a glass vial using a cyanoacrylate adhesive. The
diameter of each exposed mucosal membrane was
Clotrimazole was a gift sample from Bayer 1.5 cm. The vials were equilibrated and maintained at
Pharmaceuticals Private Limited, Thane, 37° for 10 min. One vial with a section of tissue was
India. Carbopol-934P (CP-934P) and connected to the balance and the other vial was fixed
hydroxypropylmethylcellulose (HPMC E50LV) on a height adjustable pan. To the exposed surface of
were obtained as gift samples from Goodrich and the tissue attached on the vial, a constant amount of
Colorcon Asia Pvt. Ltd, Mumbai, India. Gellan gum 0.1 g gel was applied. Before applying the gel, 150
was procured from Hi-Media Pvt Ltd, Mumbai, μl of simulated saliva solution (2.38 g NaHPO4, 0.19
India. All other materials used were of analytical g KH2PO4 and 8 g NaCl in 1000 ml of distilled water
grade. Subcultures of Candida albicans was obtained adjusted to pH 6.75) was evenly spread on the surface
from MTCC (Microbial Type Culture Collection), of the test membrane. The height of the vial was
Chandigarh, India. adjusted such that the gel could adhere to the mucosal
surface of both vials. Immediately, a constant force
Preparation of in situ gelling systems: of 0.5 N (Newton) for 2 min was applied to ensure
Aqueous solutions of varying concentration containing intimate contact between the tissue and the sample.
Carbopol 934P and HPMC (E50LV) were prepared The upper vial was then moved upwards at a constant
and evaluated for gelling capacity and viscosity in force, while it was connected to the balance. Weights
order to identify the composition suitable for as were added at a constant rate to the pan on the other
in situ gelling systems[5] (Formulation codes CF1, side of the modified balance until the two vials were
CF2, CF3, CF4, CF5 and CF6). Many experiments separated[5]. The bioadhesive force, expressed as the
were conducted by varying the concentration of detachment stress in dynes/cm2, was determined from
these polymers in order to identify the optimum the minimal weights needed to detach the tissues from
concentration required for the gel forming solution. the surface of each formulation, using the following
Dispersion containing carbopol 934P of different Eqn [6]. Detachment stress (dynes/cm 2) = (m×g)/a,
concentration (0.2-1.4% w/v) were initially prepared where ‘m’ is the weight added to the balance in
in pH 4.5 phosphate buffer solutions. grams; ‘g’ is the acceleration due to gravity taken
as 980 cm/s2; and ‘a’ is the area of tissue exposed.
Gellan gum solutions of various concentrations were Effect of varying contact time (1, 2, 3, 5 and 10 min)
prepared by adding the gum to deionised water was investigated for some of the gel preparations to
containing 0.17% w/v sodium citrate and heated optimize initial contact time. In brief, formulations
to 90° while stirring. After cooling to below 40° were allowed to be in contact with mucosa for
appropriate amounts of calcium chloride (0.05% carrying contact time (1, 2, 3, 5, and 10 min.), and
w/v) was added into the sol (formulation codes GF1, the bioadhesive force was determined as discussed
GF2, GF3, GF4, GF5, GF6). CT was dissolved in above [7]. Contact time that resulted in maximum
ethanol (2% w/w) and was added to the solution. bioadhesive strength was selected as optimum contact
The mixture was stirred by using a magnetic stirrer time required for adequate adhesion. All the above
to ensure thorough mixing. The pH of the gel (1 g) mentioned experiments were carried out in triplicates.
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Measurement of viscosity of sols: formation and noting the time for gelation and the
Viscosity determinations of the prepared in situ gels time taken for the gel formed to dissolve. Different
as well as sols were carried out on a cone and plate grades were allotted as per the gel integrity, weight
geometry viscometer (Brookfield, Massachusetts, and rate of formation of gel with respect to time.
USA), using spindle No 40. Viscosity of in situ
gelling solutions was measured at different angular Spreadability:
velocities at a temperature of 37°. A typical run For the determination of spreadability, excess of
comprised changing of the angular velocity from 0.0 sample was applied between the two glass slides and
to 100 rpm[6]. The averages of two readings were used was compressed to uniform thickness by placing 1000
to calculate the viscosity. Evaluations were conducted g weight for 5 min. Weight (50 g) was added to the
in triplicate. pan. The time required to separate the two slides, i.e.
the time in which the upper glass slide moves over
Antifungal efficacy studies: the lower plate was taken as measure of spreadability
The antifungal efficacy study against Candida albicans (S)7. S=M×L/T, where M = weight tide to upper slide,
was determined by agar diffusion method employing L = length moved on the glass slide, T = time taken.
‘cup plate technique’. Sterile solutions of CT in
DMSO (standard solution) and the developed gel In situ release studies:
having the pH adjusted to 7.0, were poured into cups For carrying out in situ release studies and
(0.1 ml of 0.1% w/v) bored into sterile malt yeast agar determination of duration of bioadhesion/erosion, a
previously seeded with test organism. After allowing flow through apparatus[4] was designed based on the
diffusion of the solutions for 2 h, the agar plates were modification of a “flow through device cell”. The
incubated at 37° for 48 h. The zone of inhibition flow through cell was made of glass and had a length
(ZOI) was measured and compared with that of pure of 10.5 cm and a diameter of 2.1 cm. It was closed
drug. The entire operation was carried out in aseptic at one end and open at the other. In the center of
condition through out the study. Each solution was the lower base there was a cavity of 1.6 cm length
tested in triplicate. Both positive and negative controls and 1.5 cm depth for placement of the chicken cheek
were maintained throughout the study[8]. mucous membrane. Dissolution medium pH 6.8
(simulated salivary pH) was pumped at a flow rate of
Determination of gel strength: 0.6 ml/min (corresponding to mean resting salivary
The method by which the properties of polymeric flow rate) using flow regulators. Sols were added
system may be conveniently determined is texture from the top so that upon contact with the salivary
profile analysis. A TA-XT2 Texture analyzer (The fluid get converted to gel form. The gels settled
experiments were conducted at Digital Scientific on the mucous membrane, exhibited mucoadhesive
Equipments, RK Puram, New Delhi). The experiment property. Samples (2 ml) were withdrawn at different
was done by placing the gels in standard beaker time intervals from the reservoir till the gel was
below the probe. In this an analytical probe is then completely eroded. The cumulative percent drug
immersed into the sample. The Texture Analyzer was release was determined by measuring the absorbance
set to the ‘gelling strength test’ mode or compression at 260 nm.
mode with a test-speed of 1.0 mm/s. An acquisition
rate of 50 points per seconds and a trigger force of Statistical analysis
5 g were selected. An aluminum probe of 7.6 cm The results obtained from the experiments of
diameter was used for all the samples. The study was mucoadhesive strength and release studies were
carried out at room temperature[9]. The force required analyzed statistically using multivariate tests. A
to penetrate the gel was measured as gel strength in statistically significance difference was conducted
terms of g. using SPSS version 13 and difference was considered
to be significant at p<0.05.
Gelling capacity:
The gelling capacity was determined by placing RESULTS AND DISCUSSION
a drop of the system in a vial containing 2 ml of
simulated salivary fluid (pH 6.8) freshly prepared The formulations of this study contained Ca++ ions
and equilibrated at 37º and visually assessing the gel in complexed form and the release of which in
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the slightly acidic conditions of the buccal cavity action of the salivary fluid (pH 6.8).
ensured reproducible gelation of the gellan gum. The
quantities of the complexing agents calcium chloride A reduction in the concentration of primary polymers
and sodium citrate must be such that there is no (gellan gum/carbopol) without compromising the
free calcium in free ionic form in the formulation gelling capacity and rheological properties of the
so as to ensure that they are in fluid state before delivery system may be achieved by the addition of
administration, but sufficient Ca ++ ions must be viscosity enhancing polymers such as HPMC. The
released when the complex is broken down (due to HPMC also helped the gel to rapidly settle due to
dissociation) in presence of simulated salivary fluid its higher density than the gels prepared without
to cause gelation. Determination of the optimum HPMC. This also helped the gels for its adhesion
amounts of complexing agents for gellan gum sols property to the mucous membrane and subsequent
(Table 1) showed that only those containing 0.05% prolonged release. Aqueous sols exhibited pH values
(w/v) calcium chloride in combination with 0.17% in range of 4.0 to 7.5, at 25° (Table 2). The pH
(w/v) sodium citrate were found to be satisfactory of all the formulations was adjusted to 6.5-7 with
to cause gelation. Low level of cations present in triethanolamine.
the solution was sufficient to hold the molecular
chains together and inhibit hydration. As a result The two main prerequisites of an in situ gelling
the experiment was performed with formulations system are viscosity and gelling capacity. To instill
containing 0.05% (w/v) calcium chloride and 0.17% easily at the affected site the formulation must possess
(w/v) sodium citrate. The use of carbopol for in situ optimum viscosity. Further, the formulation should
gel forming systems is substantiated by the property undergo rapid sol to gel transition upon contact at
of its aqueous solutions into stiff gels, when the pH the affected site. Hence, the viscosity of sols and gels
is raised. However, the concentrations of carbopol of various formulations was determined at various
required to form stiff gels prepared in acidic solutions shear rates (figs. 1 and 2). It was found that as the
(pH 4.5) are not easily neutralized by the buffering shear rate increased the viscosity of gel decreased.

TABLE 1: COMPOSITION OF VARIOUS FORMULATIONS USED IN THE PREPARED IN SITU GELS

Formulation Clotrimazole Gellan gum Carbopol HPMC Sodium citrate Calcium chloride Deionized water
(%) (%) (%) (%) (%) (%) (%) up to
GF1 0.1 0.1 - 0.5 0.17 0.05 10
GF2 0.1 0.2 - 0.5 0.17 0.05 10
GF3 0.1 0.3 - 0.5 0.17 0.05 10
GF4 0.1 0.4 - 0.5 0.17 0.05 10
GF5 0.1 0.5 - 0.5 0.17 0.05 10
GF6 0.1 0.75 - 0.5 0.17 0.05 10
CF1 0.1 - 0.2 0.5 0.17 0.05 10
CF2 0.1 - 0.4 0.5 0.17 0.05 10
CF3 0.1 - 0.6 0.5 0.17 0.05 10
CF4 0.1 - 0.8 0.5 0.17 0.05 10
CF5 0.1 - 1.2 0.5 0.17 0.05 10
CF6 0.1 - 1.4 0.5 0.17 0.05 10

TABLE 2: CHARACTERISTICS OF VARIOUS CLOTRIMAZOLE GEL FORMULATIONS

Formulations pH* Viscosity* Spreadbility Drug Content *Muco- adhesive force Gelling Gel strength
(cps) g.cm/s (%w/w) dynes/cm2 Capacity g/s
GF1 7.2 11000 25.2 98.7 52.2±2.4 _ 0.5
GF2 7.1 11200 25.8 98.6 53.5±1.09 + 2
GF3 7.2 12020 26 98.8 48.4±3.4 + 3.5
GF4 7.3 12540 27.5 98.5 51.5±5.3 ++ 4
GF5 7.2 14000 28.5 90.4 52.5±7.5 +++ 6.5
GF6 7.5 16000 30.7 98.5 54±5.6 +++ 7.2
CF1 6.8 600 10.12 95.3 30.6±0.7 _ 0
CF2 6.2 700 11.01 99.9 32.7±2.8 _ 0.5
CF3 6.4 850 11.5 98.8 36.5±1.5 + 1.2
CF4 6.4 1050 11.8 98.3 48±1.2 + 1.5
CF5 6.2 1234 12.2 99.7 52.5±2.8 ++ 2
CF6 6.1 1533 12.4 99.4 55.6±4.2 ++ 2.5
*Average of three reading; - No gelation; + Gel after few minutes, dissolved rapidly; ++ Gelation immediately, remains for few hours; +++ Gelation immediately,
remains for extended period.

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90 18000

80 16000

70 14000

60 12000
VISCOSITY (cps)

VISCOSITY (CPS)
50 10000

40 8000

30 6000

20 4000

10 2000

0 0
0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80
RATE OF SHEAR (rpm) RATE OF SHEAR (rpm)
(a) (b)
Fig. 1: Viscosity of the various formulations using gellan gum
(a) Various sols represented by (─▲─) Formulation GF1, (─▼─) Formulation GF2, (─■─) Formulation GF3, (─●─) Formulation GF4, (─♦─)
Formulation GF5, (─◄─) Formulation GF6, and (b) Various Gels represented by (─▲─) Formulation GF1, (─▼─) Formulation GF2, (─■─)
Formulation GF3, (─●─) Formulation GF4, (─♦─) Formulation GF5, (─◄─) Formulation GF6.

1800
100 1700
1600
90
1500
80 1400
1300
70 1200
VISCOSITY(CPS)

1100
60
Viscosity (CPS)

1000
50 900
800
40 700
600
30
500
20 400
300
10 200
100
0
0 10 20 30 40 50 60 70 80 0 10 20 30 40 50 60 70 80
Rate of Shear (rpm) RATE OF SHEAR(rpm)
(a) (b)
Fig. 2: Viscosity of the various formulations using carbopol
(a) Various sols represented by (─▲─) Formulation CF1, (─▼─) Formulation CF2, (─■─) Formulation CF3, (─●─) Formulation CF4, (─♦─)
Formulation CF5, (─◄─) Formulation CF6, and (b) Various Gels represented by (─▲─) Formulation CF1, (─▼─) Formulation CF2, (─■─)
Formulation CF3, (─●─) Formulation CF4, (─♦─) Formulation CF5, (─◄─) Formulation CF6.

Also, the increase in polymer concentration caused content of gellan gum in the formulation (GF6),
increase in viscosity of the formed gel. These findings not ideal for in situ gel formulation, since such
indicated the differences between viscosity of gels formulation exhibits higher viscosity for sols, hence
and their corresponding sols. The formulation GF6 not pourable. In comparison, formulation containing
having the maximum concentration of gellan gum carbopol 934P showed no remarkable sol to gel
showed maximum viscosity for both sols and its conversion. This may be attributed to the lower pH of
corresponding gels. It was also found that higher simulated salivary fluid (pH 6.8) as discussed earlier.
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It has been showed by Srividya et al, that carbopol drug from these gels was characterized by an initial
could show better sol to gel conversion at pH 7.2 and phase of high release (burst effect) and as the gelation
higher[10]. proceeded, the remaining drug was released at a
slower rate (second phase). This bi phasic pattern of
All the formulations exhibited shear thinning pseudo- release is a characteristic feature of matrix diffusion
plastic behavior with thixotrophy. Further, it was also kinetics. The initial burst effect was considerably
found that, all the formulations were liquid at room reduced with increase in polymer concentration.
temperature and underwent rapid gelation when the The formulation GF1and GF2 containing the lower
pH was raised to 6.8. The viscosity of formulation polymer ratio (0.1: 0.5 and 0.2: 0.5) showed the
contributed to the product adhesiveness, reflecting the release profile only up to 4 h, whereas formulation
importance of product rheology on this parameter[11]. having higher polymer ratio i.e., GF6, showed only
50% release at the end of 6 h. Since we were inclined
The mucoadhesive force is an important to formulate in situ gel which show 90% release
physicochemical parameter for topical application in profile within 6 h, GF1, GF2 and GF6 formulations
buccal cavity. The effect of different concentrations of were not found to be ideal formulations for in situ
CT gel formulation on mucoadhesive force is shown gels. In comparison, the gels containing carbopol
in Table 2. The bioadhesive force was significantly having the maximum concentration CF6 could show
increased as the concentration of mucoadhesive release only up to 5 h, though, the other formulations
polymer increased in the range of 0.6-3.5% of carbopol disintegrated rapidly and released the drug
(p<0.05). Formulation GF6 (containing the maximum within 4 h. However, these findings clearly showed
polymer ratio 0.75:0.5) using gellan gum and CF5, that the gels have the ability to retain CT at higher
CF6 containing carbopol, exhibited maximum concentration of carbopol (CF6) and premature release
mucoadhesive strength. This also proved that carbopol of drug can be avoided. Hence GF4, GF5 and CF6
(up to 55 dyes/cm2) has better mucoadhesive property formulations were chosen to meet the above said
than gellan gum (up to 54 dynes/cm2), even though, criterion.
they showed poor gelling capacity. The results also
indicated that the presence of secondary polymer The examination of the correlation coefficient ‘r’
(HPMC) significantly increased the viscosity as well indicated that the drug release followed diffusion
as the mucoadhesive property. controlled mechanism from the in situ gels, as the
values of ‘r’ for first order (ranged from 0.9183 to
The in vitro dissolution profile of CT from the gels 0.9891) found to be higher in comparison to zero order
containing different concentration of gellan gum and (ranged from 0.6629 to 0.9333) and Higuchi's square
carbopol based gels is shown in fig. 3. The release of root of time (ranged from 0.6558 to 0.9708). It was

120 120
100 100
80 80
Cummulative %
Cummulative %

Drug release
Drug release

60 60
40 40
20 20
0 0
0 100 200 300 400 0 100 200 300
Time (hrs) Time (hrs)
(a) (b)
Fig. 3: The in vitro release profiles of clotrimazole in situ gels
(a) Gels prepared using Gellan gum, (─■─) Formulation GF1, (─■─) Formulation GF2, (─♦─) Formulation GF3, (─Х─) Formulation GF4,
(─▲─) Formulation GF5, (─●─) Formulation GF6, and (b) Gels prepared using Carbopol (─■─) Formulation CF1, (─■─) Formulation CF2,
(─♦─) Formulation CF3, (─Х─) Formulation CF4, (─▲─) Formulation CF5, (─●─) Formulation CF6 ,

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TABLE 3: RELEASE EXPONENT VALUES AND RELEASE RATE CONSTANT VALUES FOR DIFFERENT FORMULATION
Formulation Code Kinetic Models
Zero Order First Order Higuchi Korsmeyer et al.,
r r r r r
GF1 0.8011 0.9872 0.7764 0.4431 0.9863
GF2 0.8273 0.9654 0.8442 0.3224 0.8942
GF3 0.9850 0.9354 0.9708 0.4280 0.9537
GF4 0.6629 0.9183 0.6220 0.3588 0.9912
GF5 0.9333 0.9816 0.8750 0.3915 0.9152
GF6 0.7825 0.9891 0.6558 0.4280 0.9239
CF1 0.4616 0.9771 0.8876 0.4330 0.9368
CF2 0.5326 0.8764 0.8845 0.5140 0.8302
CF3 0.5534 0.7653 0.8867 0.4670 0.9897
CF4 0.6577 0.8836 0.8621 0.4850 0.9902
CF5 0.7673 0.9916 0.7633 0.4430 0.9852
CF6 0.8821 0.9991 0.7431 0.4810 0.9939

understood to be predominant first order release pattern. REFERENCES

Further, to understand the drug release mechanism, the
data were fitted into Peppas exponential model Mt/ 1. Melo NR, Taguchi H, Culhari VP, Kamei K, Mikami Y, Smith SN, et
al. Oral candidiasis of HIV-infected children undergoing sequential HIV
M∞=Ktn , where Mt/M∞ is the fraction of drug released therapies. Med Mycol 2009;47:1-8.
after time ‘t’ and ‘K’ is kinetic constant and ‘n’ is 2. Gallardo JM. Xerostomia: Etiology, diagnosis and treatment. Rev Med
release exponent which characterizes the drug transport Inst Mex Seguro Soc 2008;46:109-16.
3. Chang JY, Oh YK, Kong HS, Kim EJ, Jang DD, Nam KT, et al.
mechanism[12]. The values ‘n’ were in the range of Prolonged antifungal effects of Clotrimazole-containing mucoadhesive
0.3224–0.428, which was further indicative of the drug thermosensitive gels on vaginitis. J Control Release 2002;82:39-50.
release following diffusion first order release kinetic 4. Ning MY, Guo YZ, Pan HZ, Yu HM, Gu ZW. Preparation and
evaluation of proliposomes containing clotrimazole. Chem Pharm Bull
mechanism (Table 3). (Tokyo) 2005;53:620-4.
5. Wu C, Qi H, Chen W, Huang C, Su C, Li W, et al. Preparation and
The antifungal activity of the tested in situ formulations evaluation of a Carbopol/HPMC-based in situ gelling ophthalmic
was found to be equal to that of the reference standard. system for puerarin. Yakugaku Zasshi 2007;127:183-91.
6. Ikanth PS, Mishra B. Floating in situ gelling system for stomach site-
It was observed that the plain formulation used in the specific delivery of clarithromycin to eradicate H. pylori. J Control
study exhibited no antifungal activity. The students Release 2008;125:33-41.
‘t’ test showed that there is no significant difference 7. Mitra J, Mohammad RR, Hedayte S. Mucoadhesive and drug release
properties of benzocaine gel. Iranian J Pharm Sci 2006;2:185-94.
in the zone of inhibition with the gel formulation in 8. El laithy HM, El-Shaboury KM. The development of cutina lipogels
comparison to the reference standard at P <0.05. and gel microemulsion for topical administration of fluconazole. AAPS
PharmSciTech 2002;3:77-85.
Gel formulation of CT with mucoadhesive properties 9. Walewijk A, Cooper White JJ, Dunstan DE. Adhesion measurements
between alginate gel surfaces via texture analysis. Food Hydrocolloids
was found to be promising for prolonging buccal 2008;22:91-6.
residence time and thereby better therapeutic effects. 10. Srividya B, Cardoza RM, Amin PD. Sustained ophthalmic delivery of
In addition, they provide intimate contact between a ofloxacin from a pH triggered in situ gelling system. J Control Release
2001;73:205-11.
dosage form and the absorbing tissue which may result 11. Hongyi Q, Wenwen C, Chunyan H, Chuming C, Wenmin L, Chunjie
in high drug concentration in local area. The in situ W. Development of a poloxamer analogs/carbopol-based in situ gelling
formulation may improve the patient acceptability, as and mucoadhesive ophthalmic delivery system for puerarin. Int J Pharm
2007;337:178–87.
the formulation is applied in the form of sols, which 12. Raghuram Reddy K, Srinivas M, Srinivas R. Once-daily sustained-
upon contact forms the corresponding gels causing less release matrix tablets of nicorandil: Formulation and in vitro evaluation.
irritation or pain. AAPS PharmSciTech 2003;4:480-8.

ACKNOWLEDGEMENTS
Accepted 31 July 2009
The authors are grateful to Nitte Education Trust, Mangalore Revised 28 July 2009
and Rajiv Gandhi University of Health Sciences, Bangalore Received 12 August 2008
for providing the necessary facilities to carry out this study. Indian J. Pharm. Sci., 2009, 71 (4): 421-427

July - August 2009 Indian Journal of Pharmaceutical Sciences 427