Formulation and Evaluation of Mucoadhesive Oral Gel Containing Miconazole Nitrate for Oral Candidiasis

 

R. Narayana Charyulu1*, P. Parvathy Devi1, Jobin Jose1, A. Veena Shetty2

1Department of Pharmaceutics, Nitte Gulabi Shetty Memorial Institute of Pharmaceutical Sciences, Deralakatte, Mangalore – 575 018

2Department of Microbiology, K.S. Hegde Medical Academy, Deralakatte, Mangalore – 575018

*Corresponding Author E-mail: charyulun@yahoo.co.in

 

 

ABSTRACT:

The study mucoadhesive oral gels, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms for treatment of oral candidiasis. Miconazole nitrate (MN) is a broad spectrum antifungal agent preferred in the treatment of oral candidiasis. In the present study, mucoadhesive oral gels of MN were prepared with carbopol 934P in combination with sodium carboxy methyl cellulose, poloxamer 407, two different grades of hydroxy propyl methyl cellulose (50cps and 1500cps) and two different grades of hydroxy ethyl cellulose (145mPas and 270mPas). The prepared formulations were characterized in terms of drug content, pH, spreadability, viscosity, mucoadhesive strength, in vitro release and in vitro antifungal activity and compared with marketed MN gel. The surface pH values of all the gels were in the range of 6.59 ± 0.06 to 6.84 ± 0.07. All the formulations showed acceptable spreadability ranging from 4.56 ± 0.05 to 7.53 ± 0.25 cm and mucoadhesive strength of 3760.59 ± 3.2 to 6499.36 ± 4.7 dynes/cm2. The prepared gels exhibited shear thinning behaviour which is suitable for topical preparations. During in vitro drug release studies, formulations were successful in sustaining the release for 6h to more than 7h. Furthermore, the in vitro antifungal activity of the formulated mucoadhesive gels was significantly (p<0.05) higher to the reference marketed MN gel. The drug release mechanism was found to follow Fickian diffusion. On the basis of the obtained data, the mucoadhesive gel formulation which was prepared with 1% w/w hydroxy ethyl cellulose (270mPas) was determined as the most appropriate formulation for buccal application in means of possessing suitable physical properties, high mucoadhesion and favourable in vitro release pattern.

KEYWORDS: Mucoadhesive Oral Gel, Miconazole Nitrate, Oral Candidiasis.


 

INTRODUCTION:

Oropharyngeal candidiasis is a very common localized infection of the mucus membranes of the oropharynx caused by Candida species1. Prevention of superficial oral infections is crucial in order to improve the quality of life as well as to prevent the possible development of systemic fungal infection. Topical antifungal therapy is the recommended first line treatment for uncomplicated oral Candidiasis2. Miconazole nitrate (MN) is a broad-spectrum antifungal agent that has been extensively applied for the management of dermal3, buccal4, and vaginal5 Candidiasis. Penetration of MN after systemic administration into saliva, sputum and the CNS is poor6.

 

Hence, an effective topical delivery system is essential for successful therapy with MN. Miconazole 2% gel is commonly used four times daily where the patient are advised to hold the 2.5ml of the gel in mouth for as long as possible and then swallow7. This might create patient non-compliance. Also, risk for sudden unwanted increase in the systemic level of MN is high with the conventional gel system. These draw backs of conventional gel preparation can be overcome by incorporation of mucoadhesive polymers into the gel base. It helps to retain the dosage form at the site of application, thus maintaining a high local concentration of the drug. Previous reports have documented the use of buccal mucoadhesive devices for prolonged release of antifungal agents8. Carbopol-934P is a lightly cross-linked polyacrylic acid which has shown to have good mucoadhesive properties and is used in orally administered products9. Carbopols have very low pH in the range of 2.5 – 3.0 (1% aqueous solution). If used alone, they may cause irritation. Its irritant properties can be reduced by combining it with other non-irritant bioadhesive polymers10. The aim of the present study was to develop a suitable polymer combination for the formulation of mucoadhesive oral gel of miconazole nitrate that possesses appropriate physical properties, retains on the buccal mucosa for a required time period with high mucoadhesion and provides sustained drug release; thus improving the efficacy, safety and patient acceptability of the formulation.

 

MATERIALS AND METHODS:

Miconazole nitrate was procured from Yarrow Chemicals (Mumbai). Hydroxy ethyl cellulose (HEC) (145 mPas and 270 mPas) and Carboxy methyl cellulose sodium salt (NaCMC) was obtained from Loba Chemie Pvt. Ltd., (Mumbai). Carbopol-934P was procured from Himedia Lab Pvt. Ltd., (Mumbai). Hydroxyl propyl methyl cellulose (HPMC) was procured from CDH (P) Ltd., (New Delhi). Poloxamer 407 (PL 407) was procured from Sigma-Aldrich, Co., (USA). Sabaoraud dextrose agar and Sabaoraud dextrose HiVeg broth were procured form Himedia Lab Pvt. Ltd., (Mumbai). All other materials used were of analytical grade. Subcultures of Candida albicans (ATCC 90028) was obtained from A.B. Shetty Memorial Institute of Dental Sciences, (Manglore).

 

Formulation of Miconazole Nitrate Mucoadhesvie Oral Gel:

2% w/w mucoadhesive gels of miconazole nitrate were prepared using combination of different mucoadhesive polymers of varying viscosity grades as mentioned in the Table. 1

 

Formulation of Miconazole Nitrate Gel with NaCMC, HPMC and HEC:

The required amount of carbopol-934P were weighed and dispersed slowly to a beaker containing 50 ml distilled water with continuous stirring at 400-600 rpm for 1h until it forms a clear solution. Care was taken to avoid indispensible lumps of the polymers. Accurately weighed miconazole nitrate was added to the carbopol solution by stirring for 3-4 h to obtain a homogeneous dispersion11. Then, 25 ml distilled water and the gelling agent (NaCMC, HEC and HPMC) were added slowly under continuous magnetic stirring at 100 rpm. The final quantity was made up to 100 g with distilled water. Care was taken to avoid the formation of air bubbles. The mixture was allowed to stand for air bubbles to separate. The pH was further adjusted to 6.75 ± 0.05 with 10% w/v sodium hydroxide solution as a simulation of oral pH12. The prepared gel was kept for 24 hr for complete polymer desolvation.

 

Formulation of Miconazole Nitrate Gel with Poloxamer 407:

PL407 possesses reverse thermal gelling property and therefore the gel containing PL407 was prepared by cold method13. The required amount of PL407 powder was gradually added into half of the volume of cold distilled water (5 °C) under constant agitation with a magnetic stirrer. The resulting solution was left overnight in a refrigerator to complete polymer desolvation which resulted in a clear liquid. Carbopol-934P was separately dissolved in about 20 ml of distilled water and the accurate amount of miconazole nitrate was dispersed in it with continuous magnetic stirring at 400-600 rpm. The mixture was allowed to stand for air bubbles to separate and cooled to 5°C. The cold PL407 solution was added to carbopol mixture with stirring. The final quantity was made up to 100 g with cold distilled water. The pH was further adjusted to 6.75±0.05 with 10% w/v sodium hydroxide solution as a simulation of oral pH. The gel was formed when the solution was brought back to room temperature.

 

CHARACTERIZATION:

Compatibility Studies by I.R Spectral Analysis:

FT-IR spectra matching approach was used for detection of any possible chemical interaction between the drugs and polymers. The individual sample of drug, polymer powder and the physical mixture of the six different drug-polymer combination gels were prepared and made into pellets with potassium bromide. It was scanned from 4000 - 600 cm-1 in a Bruker FTIR spectrophotometer.  The spectra obtained were compared and interpreted for the functional group peaks.

 

Table 1:  Formulation composition of various formulations

Formulation code

Drug (g)

Carbopol-934P (g)

NaCMC

(g)

PL407

(g)

HPMC

50cps(g)

HPMC

1500cps(g)

HEC –

145mPas (g)

HEC-270mPas

(g)

FA1

2

1

3

-

-

-

-

-

FA2

2

1

5

-

-

-

-

-

FB1

2

1

-

10

-

-

-

-

FB2

2

1

-

13

-

-

-

-

FC1

2

1

-

-

10

-

-

-

FC2

2

1

-

-

13

-

-

-

FD1

2

1

-

-

-

2

-

-

FD2

2

1

-

-

-

4

-

-

FE1

2

1

-

-

-

-

5

-

FE2

2

1

-

-

-

-

7

-

FF1

2

1

-

-

-

-

-

0.5

FF2

2

1

-

-

-

-

-

1

 


 

Viscosity

The viscosity of gels was determined by using Brookfield viscometer DV-II+Pro model: LV with T-bar spindle (Spindle T 95). The viscosity was measured using 50 g of gel filled in a 100 ml beaker. The T-bar spindle was lowered perpendicular in the centre taking care that spindle does not touch bottom of the jar. The factors like temperature, pressure and sample size etc. which affect the viscosity was maintained during the process. Viscosity measurements at varying velocities (rpm) were done. A typical run comprised changing of the angular velocity from 0.3 to 30 rpm. Evaluations were conducted in triplicate.

 

Surface pH:

The pH was noted by bringing the electrode of digital pH meter in contact with the surface of the formulations and allowing it to equilibrate for 1min. Evaluations were conducted in triplicate with different samples of the gel.

 

Spreadability:

To determine the spreadability, 0.5 g of gel was placed within a circle of 1 cm diameter pre-marked on a glass plate, over which a second glass plate was placed. A weight of 1000g was allowed to rest on the upper glass plate for 5 min. The increase in the diameter due to gel spreading was noted. Evaluations were conducted in triplicate with different samples of the gel14.

 

Mucoadhesive Strength:

In the present work, a modified assembly based on published literature was used. Mucosal side of the cheek of chicken was used as a model surface for bioadhesion testing. The pieces of tissue were transported in kreb’s buffer and thawed to the room temperature before use. The modified apparatus used in the study comprised of a two-arm balance, one side of which contained two glass plates and the other side contained a container. One of the two glass plates was attached permanently to the base of the stage, and the other was attached to the arm of the balance by a thick strong thread. The chicken mucosal membrane was glued to the upper side of the lower plate and another was glued to the lower side of the upper plate by using cyanoacrylate adhesive. The weighed gel (0.1 g) was placed on the mucosal surface glued to the upper side of the lower plate. Then, the upper plate was placed over the lower plate and 50 g preload force (or contact pressure) was applied for 5 min (preload time). After removal of the preload force, the water was kept in a bottle at some height and was siphoned into the container at a rate of 10 ml per min till the plates were detached from each other. The weight of the water (g) required for the detachment of the glass plates was measured.

 

The bioadhesive force, expressed as the detachment stress in dynes/cm2, was determined from the minimal weights needed to detach the tissue from the surface of each formulation, using the following equation15.

 

Where, ‘m’ is the weight added to the balance in grams; ‘g’ is the acceleration due to gravity taken as 980 cm/s2 and ‘A’ is the area of tissue exposed.

 

Content Uniformity:

Representative gels of each formulation were dissolved in simulated salivary fluid with 2% Sodium Lauryl sulphate (SLS). This suspension was shaken for 6 h and volume was made up to 100 ml with simulated salivary fluid, filtered through Whatman filter paper. The filtrate was analyzed using Jasco V-530 spectrophotometer by measuring the absorbance at 273nm. Evaluations were conducted in triplicate with different samples of the gel16.

 

In Vitro Dissolution Studies:

The drug release from the formulations was determined by using an apparatus, which consist of a cylindrical glass tube (with 22-mm internal diameter and 76 mm height) which was opened at both the ends. 1 g of gel, equivalent to 200 mg of MN was spread uniformly on the surface of cellophane membrane (previously soaked in medium for 24 h) and was fixed to the one end of tube. The whole assembly was fixed in such a way that the lower end of tube containing gel was just touching (1-2 mm deep) the surface of diffusion medium i.e. 100 ml of pH 6.8 simulated salivary buffer (2% SLS) contained in 250 ml beaker. The assembly was placed on thermostatic hot plate with magnetic stirrer and maintained at temperature 37 ± 2 °C the contents were stirred at 100 rpm. Samples of 5 ml were withdrawn from the middle region of the receptor at different time intervals and replaced with 5 ml of fresh buffer. The samples were filtered through 0.45 mm Whatman filter paper and were assayed spectrophotometrically at maximum absorption wavelength of 273 nm. Evaluations were conducted six times with different samples of the gel.

 

Antifungal Efficacy Studies:

The antifungal efficacy study against Candida albicans was determined by agar diffusion method. Optimized formulations FA1, FB2, FC2, FD2, FE2, FF2 and marketed gel were selected for antimicrobial evaluation. Inoculum of Candida albicans (ATCC 90028) were prepared by incubating four or five isolated colonies of the organism in 3 ml of sterile sabouraud dextrose Hi veg broth for about 4 - 5 h in incubator. The turbidity of this suspension was adjusted to a 0.5 McFarl and standard. Sabouraud dextrose agar (Himedia) was prepared as per manufacturer’s instruction. Media was then poured into sterile pertiplates and agar allowed to solidify. On the dried agar plates, the inoculums was streaked using sterile swabs. Calculated quantities of the marketed gel and gel formulation equivalent to 0.2 mg of miconazole nitrate and equal quantity of respective placebo were accurately weighed and placed on the surface of sabouraud dextrose agar plates previously cultured with Candida albicans and kept in incubator for 24 h at 37 ºC17. Following incubation, the zone sizes to the nearest millimeter was measured using a ruler. Each experiment was repeated six times and the results were expressed as mean ± standard deviation. Statistical significances were compared between the standard (marketed gel) and formulated mucoadhesive gels and analyzed by the Students t-Test using SPSS version 16.

 

Stability Studies:

The stability studies of the formulated mucoadhesive gels were carried out on prepared gels kept at different temperature. The formulations were sealed in a glass vial and placed in stability chamber at 5 ± 2 ºC and at temperature 30 ± 2 ºC, RH 65 ± 5% for a period of 8 weeks. The samples were analyzed for physical changes such as color and texture, surface pH. The drug content, viscosity and maximum drug release of the formulations were measured at predetermined time interval17.

 

RESULTS AND DISCUSSION:                         

Compatibility Studies by I.R Spectral Analysis:

IR studies were carried out for pure drug, carbopol-934P, NaCMC, HEC (145mPas), HEC (270mPas), HPMC (50cps), HPMC (1500cps), poloxamer-407 and the physical mixture of the formulated gels FA, FB, FC, FD, FE and FF to know the interaction between drug and the polymers in formulations. The IR spectra of pure drug, miconazole nitrate showed  prominent  peaks at 3174 cm-1  due to imidazole C-N stretch, 3059 cm-1 due to aromatic CH group, 2890 cm-1 due to aliphatic CH group,1547 cm-1 due to C=C aromatic, 1516 cm-1 due to C=C aromatic, 1477 cm-1 due to C-H bending, 1320 cm-1 due to C-N stretching, 1083 cm-1 C-C stretch, 712 cm-1 due to C-H bending. From the spectra, it was observed that there was no significant change in the original peak of the drug and the polymers when compared with spectra of physical mixture of the formulated gels and this indicates that there was no interaction between drug and polymer.

 

Viscosity:

The results obtained are depicted as a plot of viscosity (cps) Vs rate of shear (rpm) in Fig. 1 to 3. In general; for all gels tested, the viscosity decreased as shear rate (rpm) increased. They were, thus characterised as pseudoplastic systems, which is a desirable behaviour for formulations applied topically because, they spread easily. In pharmaceutical gel, ointment or cream tubes, the shear rate is a measure of the velocity in relation to the tube diameter. Therefore, these formulations will flow easily as the velocity in the tube increases. The pseudoplastic behaviour was evident from the curve pattern obtained in the consistency curves (viscosity Vs rate of shear) of formulation FA1, FA2, FB1, FB2, FE1, FE2, FF1 and FF2. Formulations containing HPMC (50cps) (FC1 and FC2) and HPMC (1500cps) (FD1 and FD2) also showed a decrease in viscosity with increasing rate of shear. But, the rheogram was found to be nearly linear, indicating a low pseudoplastic behaviour. Based on the results, the viscosity of the formulations was found to be influenced by the concentration of the polymers used. In each type of the polymer, the viscosity of the formulation was found to be increased with the increase in the polymer concentrations.

 

In addition, there was noticeable difference in viscosity among the gel formulations containing different types of polymers. Gels formulated with HEC (270mPas) (FF1 and FF2) were found to impart high viscosity at low concentrations of the polymer (0.5 - 1% w/w). This can be considered advantageous for an economical scale up of the formulation. In gels formulated with HEC (145mPas) (FE1 and FE2), there was no significant improvement in the viscosity and consistency, upon increase in the concentration of polymer. Thus the polymer HEC (145mPas) was considered unsuitable for the formulation of miconazole nitrate gel. Hence, further studies with the polymer were discontinued. Among the optimized formulations, gels formulated with the combination of Carbopol 934P with HEC (270mPas) (FF2), PL-407 (FB2) and NaCMC (FA2) were found possess appreciable viscosity and consistency which was comparable to the marketed formulation.

 

Figure 1: Viscosity of formulations containing combination of carbopol with NaCMC, PL 407, HEC (270 mPas) & Marketed gel

 

Figure 2: Viscosity of formulations containing combination of Carbopol with HPMC (50cps & 1500cps)

 

Figure 3: Viscosity of formulations containing combination of Carbopol HEC (145 mPas & 270 mPas)

 

Surface pH

The normal range oral mucosal pH is reported to be between 6.0 to 7.4. It was found that pH values of all the gels where in this range and thereby not causing any damage to the hard and soft oral tissues. Thus, it may be assumed that all the formulations are applicable for oral mucosal treatment. The pH of various formulations is tabulated in Table. 2

 

Spreadability

Spreadability of the topically applied formulation is an important property considering patient compliance. Formulations with higher spreadability values allow ease of application. The spreadability of three samples of each formulation was determined and the averages are reported in the Table. 2. Form the results, all the formulations were found to have acceptable spreadability. It was observed that the spreadability tend to reduce upon increase in the concentration of mucoadhesive polymers. The trend was similar in all the polymers studied. This decrease in the spreadability with increase in the concentration of mucoadhesive polymers can be attributed to the increase in the viscosity of the system18. The compressibility value should be low to take the prepared gel from the container and to be easily spread on the mucosal epithelia. The behaviour of formulations varied with the polymers used. Formulation FA2 containing NaCMC had lower viscosity compared to the optimised formulations prepared using poloxamer (FB2) and HEC (270mPas) (FF2). But, spreadability of FA2 was found to be less compared to that of FB2 and FF2. A similar response was also shown by optimised gels formulated with HPMC (FD2 and FC2). This behaviour of HPMC gels may be due to their lower pseudoplastic nature as evident from the nearly linear pattern of their rheograms. The optimised formulation prepared using HPMC (1500cps) (FD2) exhibited higher spreadability compared to that of HPMC 50cps (FC2). This may be due to higher viscosity of the formulation FC2 in comparison to FD2.

 

Mucoadhesive Strength

The effect of different types and concentrations of polymer on mucoadhesive force is shown in Table.2. It was observed that all the formulations showed good mucoadhesive strength. This effect can partially be attributed to the presence of carbopol in the formulations. Mucoadhesive properties of polymeric gels were dependent both on type of polymer, and on the concentration of each polymeric component. The results of mucoadhesive strength measurement suggested that the increase in polymer concentration will provide better adhesion and hence longer residence time. A general trend of higher mucoadhesion with increasing viscosities of the formulation was observed. Formulations FF1 and FF2 containing HEC (270mPas) showed highest mucoadhesion, followed by FA2 containing NaCMC. Optimized gel formulations with HPMC (1500cps) showed slightly higher mucoadhesioin in comparison to that of HPMC (50cps). This may be due to higher molecular weight of HPMC (1500 cps).  Poloxamer gel's showed a deviation from this. The formulation FB1 and FB2 containing poloxamer-407 possessing fairly high viscosity, showed least mucoadhesive strength. All the formulations showed appreciable mucoadhesion. Mucoadhesion of most of the formulations were found to be considerably higher in comparison to the marketed gel. Thus, the incorporation of mucoadhesive polymers can be justified.

 

 


 

Table 2: Physicochemical characterization of mucoadhesive oral gels of miconazole nitrate.

Formulation code

Surface pH*

Spreadability*(cm)

Mucoadhesive strength* (dynes/cm2)

Drug content*(%)

FA1

6.76 ± 0.08

5.57 ± 0.15

4265.97 ± 1.3

99.72 ± 0.35

FA2

6.68 ± 0.15

4.53 ± 0.06

5128.33 ± 2.03

98.43 ± 0.29

FB1

6.84 ± 0.07

6.10 ± 0.10

3512.39 ± 4.5

96.24 ± 0.33

FB2

6.87 ± 0.03

5.87 ± 0.06

3760.59 ± 3.2

99.31 ± 0.67

FC1

6.64 ± 0.84

5.37 ± 0.06

4037.53 ± 6.8

97.83 ± 0.92

FC2

6.78 ± 0.11

4.57 ± 0.06

4215.62 ± 7.2

99.36 ± 0.35

FD1

6.59 ± 0.06

5.73 ± 0.06

4083.26 ± 2.9

98.65 ± 0.54

FD2

6.6 1 ± 0.19

5.17 ± 0.06

4421.31 ± 4.1

99.58 ± 0.48

FE1

6.79 ± 0.05

7.53 ± 0.25

-

99.81 ± 0.39

FE2

6.60 ± 0.21

6.23 ± 0.06

-

99.94 ± 0.18

FF1

6.68 ± 0.13

7.13 ± 0.21

6012.25 ± 3.5

98.24 ± 0.69

FF2

6.71± 0.12

5.27 ± 0.06

6499.36 ± 4.7

97.93 ± 0.79

Marketed gel

6.61 ± 0.09

4.67 ± 0.06

3813.35 ± 2.12

98.94 ± 0.81

* Each value is an average of three determinations


 

Content Uniformity

The amount of drug present in the gel was found to be uniform for all the formulation and drug content was found to be within the acceptable range. This proves that method adopted for the preparation of mucoadhesive gels is suitable and there is no significant loss of drug in the process. The results are tabulated in Table. 2.

 

 

In Vitro Dissolution Studies

The in vitro dissolution profile of MN from the various mucoadhesive oral gel formulations is shown in fig. 4 & 5. The release of drug from these gels were characterized by an initial phase of high release (burst effect) followed by a period of gradual drug release. This bi phasic pattern of release is a characteristic feature of matrix diffusion kinetics. The initial burst effect was considerably reduced with increase in polymer concentration. Formulations with NaCMC (FA1 and FA2) showed prolonged release but only around 60% drug was released by the end of 7.5h. It may be suitable for a bid dosing of MN. The formulations with PL 407 (FB1 and FB2) showed nearly 100% drug release by 6h 30min. This can be attributed to the surfactant effect of the PL407.   But, FB1 and FB2 showed high burst release of more than 35%. Formulations with HPMC (FC1, FD1 and FD2) and HEC 270mPas (FF1 and FF2) showed fairly sustained release up to 7.5h with more than 95% cumulative drug release. The marketed gel showed a burst release of 46.18 ± 0.04 %. More than 60% of the drug release within one hour. At the end of 7 and half hours, about 79% of drug was released from it. In the light of the in vitro release study, formulation FD2 and FF2 can be considered best as they showed comparatively low burst release and a good sustained release for over 7h. In these formulations, around 50% of drug was found to have released by 3 h. This can be considered advantageous as normal dosing interval of miconazole nitrate gel is 6h. It was understood that the membrane did not represent a rate limiting step in the release experiments because zero order drug release was not dominant for the diffusion performed by constant membrane area. Majority of the formulations followed fickian diffusion and first order release (except FD2 & FF2). R2 values of higuchi matrix model for all the formulations were more than 0.9. Hence, it can be considered that the miconazole nitrate gels predominantly follow higuchi matrix model. This indicates the release of drug from the gel as a square root of time-dependent process.

 

Antifungal Efficacy Studies

The antifungal activity of the tested mucoadhesive oral gel formulations was found to be higher than that of the reference marketed gel. It was observed that the placebo formulations used in the study exhibited no antifungal activity. The student‘t’ test showed that the antifungal activity of the formulations were significantly higher than the reference standard (marketed gel) at P < 0.05. Results are shown in fig.6

 

Stability Studies:

The prepared mucoadhesive oral gels of miconazole nitrate were found to be physically and chemically stable and showed no significant change in terms of physical characteristics, percentage drug content, surface pH, spreadability, viscosity and percentage drug release. It is evident from the stability study that all the gels are stable under normal shelf-conditions.

 

Figure 4: Drug release profile of formulation containing combination of carbopol with NaCMC, PL 407 & HPMC (50 cps)

 

Figure 5: Drug release profile of formulation containing combination of carbopol with HPMC (1500 cps), HEC (270 mPas) and marketed gel.


 (a)                                                      (b)                                                    (c)

 

  (d)                                                               (e)

Figure 6: Zone of inhibitions of formulation compared with marketed gel and placebo, where formulations are denoted as (a) FA1, (b) FB2, (c) FC2, (d) FD2, (e) FF2

 


CONCLUSION:

Mucoadhesive oral gel formulations of MN favor higher retention at the site of application, prolonged release throughout the dosing interval, good physical properties and reduce risk of systemic toxicity. Hence, it can be considered as a more efficacious alternative for the conventional gel system with better patient acceptability.

 

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Received on 03.09.2013       Modified on 23.09.2013

Accepted on 27.09.2013      © RJPT All right reserved

Research J. Pharm. and Tech. 6(11): November 2013; Page 1251-1257