Formulation And Evaluation Of Taste-Masked Ciprofloxacin ...

IJPFR, Oct-Dec 2012; 2(4):-45-59 Original article ISSN 2249 – 1112 45 

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Formulation And Evaluation Of Taste-Masked 

Ciprofloxacin Bioadhesive Dental Films. 

Iman I.Soliman 1 , Ebtesam M.Abdou 2 , Nagua H.Fuda 3 

1 Pharmaceutics Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah , Saudi Arabia. 

2 Pharmaceutics Department, National Organization for Drug Control and Research, Cairo, Egypt. 

3 Pharmaceutics Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. 

Ciprofloxacin is a broad-spectrum anti-infective agent of the fluoroquinolons. It has activity 

against periodontal pathogens. Saccharin is one of the most widely used artificial sweetening agents. 

The complex of ciprofloxacin saccharinate was prepared to improve organoleptic properties of 

ciprofloxacin and it was characterized using FTIR analysis, DSC, photomicrographs, solubility 

determination of the complex and UV-scanning in different media as well as determination of the 

actual drug content. 

Eight formulations of ciprofloxacin saccharinate bioadhesive dental films were prepared using 

chitosan, carbopol 934, and hydroxypropyl methyl cellulose. The prepared films were evaluated for 

their physicomechanical properties including film thickness, weight uniformity, tensile strength, folding 

endurance, surface pH, % elongation. In addition, mucoadhesive performance of films, drug content 

and in-vitro release of ciprofloxacin from different films were determined. The best formulations were 

selected and were subjected to stability study at 40 °C and 75% RH for 3 months and microbiological 

test. Results revealed that the use of mixture of carbopol and HPMC with chitosan improved physical 

and chemical properties of the prepared films. Microbiological results showed that, F 7 had the highest 

inhibition zone which may be due to the presence of high concentration of carbopol 934 that lead to 

high mucoadhesive time. 

Key words: ciprofloxacin, bioadhesive, films, dental, mucoadhesion. 

Correspondence author e-mail: ebt_mohmed@yahoo.com 

INTRODUCTION 

Periodontal diseases are infections affecting a significant proportion of people 

in all populations. The presence of periodontal pathogens such as Porphyromonas 

gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans are 

responsible for periodontal destruction. Therefore, an objective of periodontal 

treatment is to suppress or eliminate subgingival periodontal pathogens. Systemic 

antimicrobials such as adjuncts to mechanical therapy have had a positive effect on 

clinical as well as microbiological parameters. But the impact of this approach is 

reduced by the fact that the antibiotic is normally difficult to maintain in therapeutic 

Soliman et al 

© 2012 International Journal of Pharmaceutical Frontier Research


concentrations at the site over the course of the treatment period. Moreover, systemic 

antibiotic therapy carries with it the risk of the host developing resistance. Due to 

these negative effects, the use of local drug delivery devices containing antibiotics 

which can maintain therapeutic concentrations at the site of infection is an approach 

that may be explored. This could enhance the therapy of periodontal diseases while 

also reducing side effects (1-4). 

Ciprofloxacin is a second generation fluroquinolone derivative, exhibiting activity 

against a wide range of Gram-negative and Gram-positive facultative bacteria as well 

as periodontal pathogens (5). Mucoadhesive polymers are the important component in 

the development of buccal delivery system. These polymers enable retention of 

dosage form at the buccal mucosal surface and thereby provide intimate contact 

between the dosage form and the absorbing tissue (6). 

Chitosan is a hydrophilic biopolymer obtained by alkaline deacetylation of chitin, a 

major component of arthropod shells, and possesses favorable properties such as 

nontoxicity, biocompatibility, bioadhesivity and biodegradability. Moreover, chitosan 

itself possesses antimicrobial activity (7-8). 

Therefore the aim of this work was to develop taste-masked ciprofloxacin bioadhesive 

dental films for the treatment of periodontal pathogens diseases. 

EXPERIMENTAL 

Materials 

Ciprofloxacine was kindly supplied by Elpharonia company, Egypt, Sodium 

Saccharine was purchased from LOBA CHEMIE PVT. LTD. (INDIA), Chitosan low 

molecular weight was kindly supplied by sigma Pharmaceuticals (Cairo, Egypt), 

Hydroxypropyl methylcellulose (hydroxypropyl (12wt%), Methoxy (28wt%)), 

(Fluka-Biochemica, Switzerland). -Carbopol 934 (Luna Co. from Bf.Goodrich, USA). 

All water used was distilled de-ionized water. All other chemicals were of reagent 

grade and used as received. 

Equipment 

-Digital electric balance (Mettler), (India)- pH meter (CG 820 Schott-Gerate, W. 

Germany)-Thermostatically controlled magnetic stirrer (Philip Harris Ltd), 

(Shenstone, England)-Differential Scanning Calorimeter, Shimadzu, model DSC-50, 

(Japan)-Infrared Spectrophotometer (Shimadzu IR-4351, Shimadzu, Japan)-Tensile 

strength machine (Chatillon Force Measurment- Greensbora, NC27409, India)- 

Dissolution apparatus II, (Hanson Research, SR8 plus, Dissolution Test Station, 

USA)-Spectrophotometer, (Shimadzu, model UV-1601, Japan)-Oven, Fisher isotemp 

oven, 200 series, model 230F, (USA), scanning electron microscope (SEM), (JSM- 

6360L, V 1 Japan. 

Methodology 

Preformulation study 

Preparation of ciprofloxacin-saccharinate complex 

A molar solution of ciprofloxacin in 0.1 N acetic acid was mixed with aqueous molar 

solution of saccharin sodium. The mixture was stirred for 15 minutes using magnetic 

stirrer and the obtained ciprofloxacin-saccharinate complex was separated by 

filtration, air dried and kept in desiccator. 

Characterization of ciprofloxacin-saccharinate complex 

1- Microscopic examination: 

Soliman et al 



Scanning electron microscope (SEM) was used to examine the shape of the produced 

ciprofloxacin saccharinate complex and compare it with ciprofloxacin raw material. 

In addition, photomicrographs of them were taken. 

2- UV-scanning and calibration curve in different media: 

Ciprofloxacin and ciprofloxacin saccharinate complex solutions in 5% acetic acid and 

phosphate buffer pH 6.8 were scanned spectrophotometerically using UV 

spectrophotometer. The λmax for each solution was determined. 

Serial concentrations of the drug and its complex in both solvents were prepared. The 

absorbance of the prepared solutions was measured spectrophotometerically at the 

predetermined λmax. The measured absorbance was plotted against the corresponding 

concentrations and the procedural constant (K) was calculated from the measured data 

corresponding to the best fitting straight line. 

3- Solubility determination 

Solubility determination of ciprofloxacin and its complex in 5% acetic acid and 

phosphate buffer pH 6.8 using vial and shaker method were done. An excess amount 

of the powder was added in sealed glass vial in presence of 3 ml of each solvent, these 

vials were shacked for 24 hours at room temperature then the contents of each vial 

were filtered and the filtrate was diluted and measured spectrophotometerically. 

4- Determination of the actual drug content in the complex: 

The actual drug content in the complex was calculated by dissolving certain amount 

of the drug and its complex in 100 ml phosphate buffer pH 6.8, the absorbance of 

each was measured spectrophotometrically and the drug content was calculated using 

the previously constructed calibration curve. 

5- Fourier transform infrared (FTIR) analysis: 

Infrared absorption spectra of ciprofloxacin and ciprofloxacin-saccharinate complex 

were recorded using a FTIR spectrometer. Spectral scanning was conducted from 

4000 to 400 cm −1 at a resolution of 4 cm −1 of fresh samples (weighing approximately 

4 mg) that compressed into discs using KBr. 

6- Differential scanning calorimetric (DSC): 

The thermal behaviors of ciprofloxacin and ciprofloxacin-saccharinate complex were 

recorded using a differential scanning calorimeter after calibration with indium and 

lead standards. Pre-weighed samples (4 mg) were heated in crimped aluminum pans 

in an atmosphere of nitrogen. Samples were heated at a constant heating rate of 

10°C/min over a temperature range of 25–300°C. 

Formulation of ciprofloxacin-saccharinate bioadhesive films 

Preparation of the films 

Ciprofloxacin saccharinate films were prepared using 2% chitosan in 5% acetic acid 

solution alone and with carbopol 934 and HPMC in different concentrations as shown 

in table 1. The films were prepared by solvent casting technique (9). The 

predetermined amounts of chitosan and other polymers were soaked in 50 ml 5% 

acetic acid solution, then determined amount of cipro-saccharine complex (equivalent 

to 250 mg cipro), and plasticizer (5%w/v glycerin) were added. The mixture was 

stirred with the aid of mechanical stirrer to ensure complete drug and plasticizer 

distribution, this solution was taken and poured in dry glass Petri -dish (10 cm 

diameter) and dried at room temperature. 

After complete drying, films were cut into pieces (2*2 cm) and kept in aluminum foil. 

Soliman et al 



TABLE 1 Composition of different ciprofloxacin saccharinate bioadhesive 

dental films 

Formula No. 

Chitosan Carbopol 934 HPMC Glycerin 

%w/v 

%w/v %w/v %w/v 

1 2 - - 5 

2 2 2 - 5 

3 2 4 - 5 

4 2 - 2 5 

5 2 - 4 5 

6 2 2 2 5 

7 2 4 2 5 

8 2 2 4 5 

Evaluation of the prepared films 

Physicomechanical properties 

Tensile strength 

Tensile strength apparatus was used to determine the tensile strength of the prepared 

films. Longitudinal strips of the films were used, weight on the film was gradually 

increased so as to increase the puling force till the film broke, and the tensile strength 

was calculated (10) 

% Elongation 

Longitudinal strips were cut out from the prepared medicated films. The flatness was 

determined at various points by using tensile strength apparatus. The percentage 

elongation brake was determined by noting the length just before the break point and 

substituted in the following equation (11). 

% Elongation = L2 - L1 x 100/ L1 

Where L 2 = final length of each strip; and L 1 = initial length of each strip. 

Folding endurance: 

Folding endurance of the 2x2cm films was determined by repeatedly folding one film 

at the same place till it broke or folded up to 300 times manually, which was 

considered satisfactory to reveal good patch properties. The number of times of patch 

could be folded at the same place without breaking gave the value of the folding 

endurance. This test was done on two individual films of each formulation batches 

(12). 

Thickness 

Film thickness was measured using micrometer at three different places; the mean 

value and standard deviation (S.D.) were calculated. 

Weight 

Five different films from individual batches were weighed individually, and the 

average weight was calculated, the individual weight should not deviate significantly 

from the average weight, so the standard deviation was calculated. 

Surface pH 

The films were allowed to swell by keeping them in contact with 1 ml of distilled 

water for 2 h at room temperature, and pH was noted by bringing the electrode in 

contact with the surface of the patch, allowing it to equilibrate for 1 minute (13). 

Soliman et al 



Chemical properties 

Drug content 

Determined area (2*2 cm) of each film was taken and dissolved in about 30 ml 5% 

acetic acid solution with the aid of magnetic stirrer, the solution was filtered through 

filter paper and completed with the same solvent to 50 ml, the amount of drug was 

determined by measuring the absorbance spectrophotometrically at λmax 277 nm with 

respect to the predetermined calibration curve of ciprofloxacin-saccharine complex in 

5% acetic acid. This experiment was done five times taking parts from different 

places in the film. 

In- vitro release of ciprofloxacin from its films 

Release study of ciprofloxacin from different films was done using Dissolution 

apparatus USP type II rotating paddle method. The dissolution medium consisted of 

900 ml of phosphate buffer pH 6.8. The study was performed at 37 0 C with 100 rpm 

(14-15) 

The films (2*2 cm diameter) were fixed on watch glasses covered with stainless 

screen about 150 mesh/inch which was cut to fit circle on the watch glass, the back of 

this assembly was covered with aluminum foil to prevent drug dissolution from this 

side and then the hall assembly was immersed in the dissolution medium. Samples 

were collected periodically at 10, 20, 30, 45, 60, 90, 120, 150, and 180 minutes and 

replaced with fresh medium. Solutions were filtered through Whatman filter paper, 

measured spectrophotometrically at λmax 277nm to determine the amount of drug 

released against time. 

The dissolution profiles were constructed by plotting the % drug released against 

time. Drug dissolution from the investigated formula was expressed as dissolution 

efficiency (DE) for reasons of comparison. 

The DE was calculated from the area under the dissolution time curve (measured 

using the trapezoidal rule) and expressed as a percentage of the area of the rectangle 

described by 100% dissolution at the same time (16-17). DE values were statistically 

analyzed using the student t-test with a significance level of p-value >0.05. 

Mucoadhesion Time (18-20) 

For determination of mucoadhesion time or residence time of the prepared films a 

fresh sheep buccal mucosa was obtained from a local slaughterhouse and used within 

2 hours of slaughter. The mucosal membrane was separated by removing the 

underlying fat and loose tissues. The membrane was washed with distilled water. The 

residence time of different films was determined using a USP disintegration 

apparatus. Distilled water (900ml) was used as medium and the temperature of 37°C ± 

1°C was maintained throughout the experiment. A piece of fresh sheep buccal mucosa 

(3*3 cm) was fixed to the surface of a glass slide, which was vertically attached to the 

apparatus using thread. The mucoadhesive film was hydrated from one surface using 

distilled water and then the hydrated surface was brought into contact with the 

mucosal membrane. The glass slide was vertically fixed to the apparatus and allowed 

to move up and down so that the film was completely immersed in the water. The 

time necessary for complete erosion or detachment of the film from the mucosal 

surface was reported. 

The selected best film formulations based on dissolution efficiency and mucoadhesive 

performance were subjected to the following tests: 

Stability studies: 

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The selected film formulations were subjected to storage for 3 months at 40 °C and 

75% RH, they were evaluated for their physicomechanical properties and drug content 

at the end of the storage time. 

In vitro antibacterial activity 

The selected film formulations were evaluated for their antibacterial activity and 

compared with control (ciprofloxacin-saccharinate complex powder) by placing the 

film, 1 × 1 cm, on agar plates seeded with the oral bacteria Streptococcus mutans. 

After 48 h of incubation at 37°C, the diameter of inhibition zone of the agar plate was 

measured (21). 

RESULTS AND DISCUSSION 

Characterization of ciprofloxacin-saccharinate complex 

Improvement the organoleptic properties of ciprofloxacin were done via the 

preparation of ciprofloxacin saccharinate complex. Saccharin is a sulfimide, the 

hydrogen atom on the nitrogen atom is quite acidic, its pka is nearly 2 and forming H- 

bond with ciprofloxacin. 

The following results prove the formation of the complex not physical mixture of 

ciprofloxacin and saccharin: 

Figure 1(a, b, c) illustrate that, the crystals of ciprofloxacin saccharinate complex had 

a definite shape that were differed than that of ciprofloxacin and saccharine 

FIG 1A . photomicrograph of ciprofloxacin saccharinate complex (40x) 

Soliman et al 



FIG .1 B Photomicrograph of ciprofloxacin (40x) 

FIG 1 C. Photomicrograph of saccharin (40x) 

The results of scanning, calibration curves, and solubility determination of the drug 

and its complex in 5% acetic acid and PB pH 6.8 were shown in Table 2. It was 

observed that the complex had higher solubility in both solvents than the drug. 

FTIR analysis: 

Infrared absorption spectra of ciprofloxacin and ciprofloxacin-saccharinate complex 

are illustrated in figure 2. It was observed that ciprofloxacin was characterized by 

main bands at 3500-3450 cm -1 related to O-H stretching vibration and at 1750-1700 

cm -1 assigned to the carbonyl group (C=O). Also, there was a band at 1650-1600 cm - 

1 assigned to quinolone group. These bands were less sharp in the IR of the complex. 

Differential scanning calorimetric (DSC): 

DSC thermograms of ciprofloxacin and ciprofloxacin-saccharinate complex were 

represented in figure 3. Ciprofloxacin was characterized by an endothermic melting 

peak at 254 °C (corresponding to its melting point) which was less intensity and 

shifted to a lower temperature (239°C) in its complex. The reported melting point of 

Soliman et al 



ciprofloxacin and saccharine were ranged from 255 – 257 °C and 228.8 – 229.7 °C 

respectively. 

TABLE 2. Characterization of ciprofloxacin and its saccharinate complex 

Drug 

UV λmax* 

nm 

Solubility data at 

25 °C 

DSC 

melting 

point °C 

ciprofloxacin 

ciprofloxacinsaccharinate 

in 5% acetic 

acid: 275 

In PB pH 6.8: 

277 

In 5% acetic 

acid: 275 

In PB pH 6.8: 

277 

5% acetic acid: 

26 mg/ml 

PB pH 6.8: 

0.18mg/ml 

5% acetic acid: 

40mg/ml 

PB pH 6.8: 

0.28mg/ml 

254 

239 

* UV scanning from 200 - 400 nm 

FIG 2. IR bands of ciprofloxacin (a) and ciprofloxacin saccharinate complex (b) 

Soliman et al 



FIG 3. DSC thermograms of ciprofloxacine (a) and ciprofloxacin saccharinate 

complex (b) 

The preveously mentioned results are in agreement with those reported by Carolina 

B. Romañuk et. al. studies where, saccharinates salts of the fluoroquinolone 

antibiotics norfloxacin, ciprofloxacin, ofloxacin, and enrofloxacin were obtained as 

pure crystalline anhydrous solids with sweet taste. The products were characterized by 

one- ( 13 C) and two-dimensional ( 1 H– 13 C) dimensions solid state Nuclear Magnetic 

Resonance and infrared spectroscopy showing ionic interactions between the 

saccharine amide and the fluoroquinolone piperazine. Several intermolecular bindings 

were also identified. In addition, the series of products showed improved properties 

with respect to water solubility (22-23). 

The result of drug content in its complex was found to be 0.73 mg ciprofloxacin/ 1 mg 

complex. 

Characterization of the prepared ciprofloxacin saccharinate bioadhesive dental films 

Tensile strength 

The prepared medicated films had tensile strength values ranged from 43±9 to 105±8 

N/mm 2 as shown in table 3. It is clear that addition of carbopol to chitosan polymer in 

the film has decreased its tensile strength (F2 and F3) which may be related to the 

high hydrophilic nature of carbopol polymer, while addition of HPMC polymer to 

chitosan has increased its tensile strength (F4 and F5) which may be attributed to that 

HPMC is highly film forming polymer. On the other hand, when both polymers were 

used in the same formula, they give an average tensile strength values. 

% Elongation 

Table (3) shows the percent elongation values of fresh films which are directly 

proportional to the values of tensile strength. 

Folding endurance 

The folding endurance of a film is frequently used to estimate the ability of the film to 

withstand repeated bending, folding, and creasing and may be encountered as a 

measure of the quality of films (24). 

Folding endurance of the prepared films (Table 3) is related to their tensile strength as 

carbopole polymer has decreased the folding endurance of chitosan film while HPMC 

has increased it. 

Surface pH 

Soliman et al 



The surface pH of the prepared films (Table 4) ranged from 5.7 to 6.7 which is 

suitable for buccal application. 

Uniformity of drug content 

Drug content (Table 4) of the prepared films ranged from 96.6±0.7 to 101±1.2% of 

the labeled amount with very small variations between different places in the same 

film as shown in table 3. Analysis of the drug content of the prepared formulations 

has shown that the process employed to prepare films in this study was capable of 

giving films with a uniform drug content and minimum batch variability. 

In- vitro release of ciprofloxacin from different films 

Drug release from swellable and erodible hydrophilic matrix can be attributed to 

polymer dissolution (matrix erosion mechanism), drug diffusion through the gel layer 

or combination of both (25). 

Dissolution profiles of different ciprofloxacin formulations are shown in figures 3&4 

and their dissolution efficiencies are represented in table (4). It can be detected that 

addition of hydrophilic polymers, to certain limits, to chitosan leads to increase in the 

film dissolution efficiency (as in formulae F2, F4, and F7). This can be attributed to 

the hydrophobic nature of chitosan as it is more soluble in the acidic medium than in 

buffer at pH 6.8 (26). Also, the slow release of ciprofloxacine from chitosan films 

may be due to the higher swelling profile and slower erosion rate of chitosan (27) 

while the hydrophilic nature of carbopol and its high solubility at pH 6.8 as at pH 6.8 

carbopol is present in the ionized state and as a result the polymeric network gets 

loosened comparatively, attributing for the higher drug release (28). Also, carbopol 

934 act by swelling then degradation in the dissolution medium which makes pores in 

the film that increase drug release from the film. 

Further increase of the carbopol concentration from 2% to 4% has decreased the DE% 

from 48.5±4.2 to 31.9±1.6 (p- value= 0.534) for formula F2 and F3, respectively. This 

is related to that increase carbopol concentration leads to presence of more polymer to 

swell resulting in an increase in diffusional path length of drug and the consequent 

reduction of drug release (29). In addition, the thick gel layer formed on the swollen 

film surface is capable of preventing matrix disintegration and controlling additional 

water penetration (30). . 

Addition of 2% HPMC ( F4) to chitosan (F1) has increased the DE% but to less extent 

compared to addition of 2% carbopol (F2) due to the more hydrophilic nature of 

carbopol compared to HPMC which is known to give more sustained release than 

carbopol (31). Increase the percent of HPMC from 2% to 4% has decreased the 

dissolution efficiency from 37.9±2.5 to 20.1±3.6 for formulas F4 and F5, respectively 

(p-value= 0.692). This may be related to that HPMC has slow erosion rate (27) and 

the ability of HPMC to form complex matrix network which leads to delay the release 

of drug from the device (32). 

Mucoadhesion time 

The hydrophilic polymers are known to swell readily when they come in contact with 

a hydrated mucus membrane forming hydrogel. The water sorption reduces the glass 

transition temperature below ambient conditions, and hydrogels become progressively 

rubbery due to uncoiling and increased mobility of the polymer chains. This glass 

rubbery transition provides an adhesive surface for maximum contact with the mucus 

membrane, as well as flexibility to the polymer chains for interpenetration within the 

membrane. Increasing the amount of polymer may provide more adhesive sites and 

polymer chains for interpenetrationn, consequently resulting in increase of the 

mucoadhesive strength and consequently the adhesion time (33-34). HPMC and 

Soliman et al 



carbopol possesses hydroxyl and carboxyl groups respectively required for 

bioadhesion (35). 

Mucoadhesion time of different prepared films is shown in table (4). It is observed 

that increasing the percent of carbopol or HPMC increase the adhesion time with 

higher increase to carbopol more than HPMC in the same concentration. 

From the above discussion, we conclude that use of the mixture of carbopole and 

HPMC with chitosan can give balanced physical and chemical properties of the 

prepared films in which carbopol supports the release properties and increase the 

mucoadhesive time while HPMC supports the tensile strength and other physical 

properties. So, the selected formulae to be invesitigated for their stability and 

microbiological effect depending on the physicochemical properties were F2, F4, and 

F7. 

TABLE 3 Characterization of the prepared ciprofloxacin saccharinate 

bioadhesive dental films 

Formula 

weight (g)* 

thickness 

(mm)* 

Tensile 

strength 

(N/mm 2 )* 

% 

elongation* 

Folding 

endurance* 

1 1.01±0.2 0.11±0.01 73±12 53±5 110±15 

2 1.19±0.5 0.15±0.02 68±8 46±3 101±10 

3 1.41±0.3 0.22±0.02 43±9 45±4 92±12 

4 1.22±0.2 0.16±0.03 86±7 58±5 126±20 

5 1.38±0.4 0.21±0.01 105±8 61±6 143±17 

6 1.37±0.3 0.24±0.02 75±9 50±7 103±12 

7 1.41±0.2 0.26±0.01 70±6 50±5 96±15 

8 1.40±0.4 0.27±0.02 87±5 76±3 120±13 

*(n=3) 

TABLE 4. Physicochemical properties, dissolution efficiency, and mucoadhesive 

time of the prepared ciprofloxacin saccharinate bioadhesive dental films 

Formula Surface pH* Drug content* DE%** 

Mucoadhesive 

time (min)* 

1 5.7 98.4±1.4 29.7±2.3 73±12 

2 6.2 97.3±0.8 48.5±4.2 68±8 

3 6.5 97.6±1.5 31.9±1.6 43±9 

4 6.3 96.6±0.7 37.9±2.5 86±7 

5 6.7 101±1.2 20.1±3.6 105±8 

6 6.1 98±1.5 28.4±2.2 83±8 

7 6.3 100±0.5 38.6±1.8 110±5 

8 6.2 100±1.3 22.9±1.7 91±6 

*(n=3); **(n=6) 

Soliman et al 



120 

100 

% drug released 

80 

60 

40 

20 

F1 

F2 

F3 

F4 

0 

0 30 60 90 120 150 180 

Time (min) 

FIG 4. In vitro ciprofloxacin released from different prepared dental films (F1- 

F4) 

% Drug released 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

-20 30 80 130 180 

Time (min) 

F5 

F6 

F7 

F8 

FIG 5. In vitro ciprofloxacin released from different prepared dental films (F5- 

F8) 

Stability studies: 

After three monthes of storage at 75%RH ad 40 C, the evaluated films have no 

significant difference (p-value >0.05) in their drug content with no chang in their 

appearance. 

Microbiological effect 

The results of the antimicrobial effect of ciprofloxacin saccharinate complex and its 

selected film formulations F2, F4, and F7 through determination of the inhibition 

zones were illustrated in figure 6. It was noticed that formula F7 had the highest 

inhibition zone (p 0.05) but F7 had higher inhibition zone which may be assigned to the higher 

mucoadhesion time due to presence of high concentration of carbopole which is 

known by his ability to increase the mucoadhesion force (36) and thus give more 

Soliman et al 



contact time. Therefore, increasing the residence time of the drug leading to increase 

its local concentration and its effectiveness. 

Inhibition zone (mm) 

20 

18 

16 

14 

12 

10 

8 

6 

4 

2 

0 

complex powder F2 F4 F7 

FIG 6. Inhibition zone of ciprofloxacin saccharinate complex and its 

different film formulations. 

CONCLUSION 

Sodium saccharinate can be used to enhance the form complex with ciprofloxacine to 

give taste masked complex insured by the DSC and IR analysis. Also, from the above 

results we found that the use of mixture of carbopol 934 and HPMC with chitosan is 

good way to enhance the physical, chemical, and microbiological properties of 

ciprofloxacin-saccharinate films relative to use carbopole 934 or HPMC alone along 

with chitosan where carbopol 934 supports the release properties of the drug and 

increase the mucoadhesive time while HPMC supports the tensile strength of films 

DECLARATION OF INTEREST 

The authors report no conflicts of interest. The authors alone are responsible for the 

content and writing of this article. 

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