Formulation and Evaluation of Topical Antifungal Gel Containing  Itraconazole

 

Poonam Madhukar Kasar*, Kalyani Sundarrao Kale, Dipti Ganesh Phadtare

R.G.S Institute of Pharmacy, Anjaneri, Nashik, Maharashtra India

*Corresponding Author E-mail:  sonikasar2706@gmail.com

 

ABSTRACT:

The present research has been undertaken with the aim to develop a topical gel formulation of Itraconazole. Itraconazole is an imidazole derivative and used for the treatment of local and systemic fungal infection. The oral use of Itraconazole is not much recommended as it has many side effects. Commercially Itraconazole topical gel preparation are not available in the market, thus this formulation is made for better patient compliance and to reduce the dose of drug and to avoid the side effects like liver damage and kidney damage. The gel was formulated by changing the polymer ratio. Formulation were evaluated for % yield, spredability, extrudability, washability and viscosity in-vitro drug release study, skin irritation study, stability testing and finally it was concluded that formulation F3 was the best formulation among these formulation.                                   

 

KEYWORDS: Itraconazole, Carbopol 934p, HPMC.

 


 

INTRODUCTION: [9, 11]

Fungal  infection  of  skin  is  now-a-days  one of  the common dermatological problem. The physicians have a wide choice for treatment from solid dosage to semisolid dosage form and to liquid dosage formulation. Among the topical formulation clear transparent gels have widely accepted  in  both  cosmetics  and  pharmaceuticals.[1] Topical treatment of dermatological disease as well as skin care, a wide variety of vehicle ranging from solids to  semisolids  and  liquids  preparations  is  available  to clinicians  and  patients.  Within  the  major  group  of semisolid preparations, the use of transparent gels has expanded  both  in  cosmetics  and  in  pharmaceutical preparation.[2] 

 

For many decades treatment of an acute disease   or   a   chronic   illness   has   been   mostly accomplished  by  delivery  of  drugs  to  patients  using various pharmaceutical dosage forms, including tablets, capsules,  pills,  suppositories,  cream,  gel,  ointments, liquids,  aerosols  and  injectables,  as  drug  carriers. Delivery of drugs to the skin is an effective and targeted therapy for local dermatological disorders. This route of drug delivery has  gained popularity because  it  avoids first pass effects, gastrointestinal irritation, and metabolic degradation associated with oral administration. Due to the  first  past  effect  only  2545%  of  the  orally administered dose reaches the blood circulation. In order to bypass these disadvantages the gel formulations have been proposed as topical application. Gels are defined as “semisolid system in which a liquid phase is constrained within a polymeric  matrix in which a  high degree of physical   and   chemical   cross-linking   introduced”. Itraconazole  is  a  synthetic  antifungal  agent  of  the imidazole class; it works by slowing the growth of fungi that cause infection. It is used to treat fungal infection. Triazole  drug  targets  the  fungal-specific  synthesis  of membrane lipids. Itraconazole inserts preferentially into fungal  membranes  and  disrupts  their  function.  5- fluorocytosine targets fungal specific DNA replication.[3] Hydroxypropyl   methylcellulose   (HPMC),   Carbapol 934p, has been used as hydrophilic polymers topically in gel drug delivery system.[4]

 

MATERIALS AND METHODS[5,6]

Material: Itraconazole,  HPMC,  carbopol934,  trimethanolamine, glycerine, methyl paraben, propyl paraben, water.

 

Method:

Polymer (like  Carbopol 934p or  HPMC) and purified water were taken in a beaker and allowed to soak for 24 hrs.  To  this  required  amount  of  drug  (2  gm)  was dispersed in water and then Carbopol 934p or HPMC was   then   neutralized   with   sufficient   quantity   of Triethanolamine. Glycerine as moistening agent, methyl paraben and Propyl paraben as preservatives were added slowly   with   continuous   gently   stirring   until   the homogenous  gel  was  formed.  Gel  formulations  of Itraconazole were prepared using different concentrations of carbopol934, HPMC. (Table-1).

 

Evaluation of Itraconazole gel[7-24]

1.     Percentage yield: The empty container was Weighed in which the gel formulation was stored then again the container was weighed with gel formulation. Then subtracted the empty container weighed with the container with gel formulation then it gives the practical yield. Then the percentage yield was calculated by the formula.

 

                                   Practical yield

Percentage yield = ---------------------- X 100

                                Theoretical yield

 

2.     Drug content: Weighed 10 gm of each gel formulation were transferred in 250 ml of volumetric flask containing 20 ml of alcohol and stirred for 30 min. The volume was made up to 100 ml and filtered. 1 ml of above solution was further diluted to 10 ml with alcohol and again 1 ml of the above solution was further diluted to 10 ml with alcohol. The absorbance of the solution was measured spectrophotometrically at 260 nm. Drug content was calculated by the following formula

 

                             Absorbance                                     1

Drug content =-------------------- X dilution factor X ----

                               Slope                                          1000

 

3. Determination of pH :Weighed 50 gm of each gel formulation were transferred in 10 ml of beaker and measured it by using the digital pH meter. pH of the topical gel formulation should be between 3 – 9 to treat the skin infections.

 

4. Spredability: The spredability of the gel formulation was determined, by measuring diameter of 1 gm gel between horizontal plates (20×20 cm2) after 1 minute. The standardized weight tied on the upper plate was 125 gm.

 

5. Extrudability: The gel formulations were filled into collapsible metal tube or aluminium collapsible tube. The tube were pressed to extrude the material and the extrudability of formulation was checked.

 

6. Viscosity Estimation: The viscosity of gel was determined by using a Brookfield viscometer DVII model with a T-Bar spindle in combination with a helipath stand.

 

a) Selection of spindle: Spindle T 95 was used for the measurement of viscosity of all the gels.

 

b) Sample container size: The viscosity was measured using 50 gm of gel filled in a 100ml beaker.

 

c) Spindle immersion: The T-bar spindle (T95) was lowered perpendicular in the centre taking care that spindle does not touch bottom of the jar.

 

d) Measurement of viscosity: The T-bar spindle (T95) was used for determining the viscosity of the gels. The factors like temperature, pressure and sample size etc. Which affect the viscosity was maintained during the process. The helipath T- bar spindle was moved up and down giving viscosities at number of points along the path. The torque reading was always greater than 10%. The average of three readings taken in one minute was noted as the viscosity of gels.


 

Table No.1: Optimized formulae of Itraconazole gel

Formulation code

Ingredients

Drug

Carbopol

HPMC

Water

Alcohol

Methyl

Propyl

Glycerine

Triethanol

F1

2

1

-

60

4

0.1

0.05

10

4

F2

2

1

-

60

4

0.1

0.05

10

4

F3

2

0.5

0.75

60

4

0.1

0.05

10

4

F4

2

0.5

0.5

60

4

0.1

0.05

10

4

F5

2

0.75

0.5

60

4

0.1

0.05

10

4

 


7. In vitro diffusion study: The abdominal skin of Albino mice, weighing 20 – 25 gm of 8 – 10 week old was shaved using hand razor and clean the skin with hot water cotton swab. 5 gm of gel was applied uniformly to skin. The skin was mounted between the compartments of the Frantz diffusion cell with stratum corneum facing the donor compartment. Reservoir compartment was filled with 100 ml phosphate buffer of pH 6.8. The study was carried out at 37 ± 1°C and speed was adjusted until the vortex touches the skin and it carried out for 4½ h. 5 ml of sample was withdrawn from reservoir compartment at 30 min interval and absorbance was measured spectrophotometrically at 260 nm. Each time the reservoir compartment was replenished with the 5 ml volume of phosphate buffer pH 6.8 solution to maintain constant volume.

 

RESULT AND DISCUSSION:

Table No. 2:  Percent yield of gel formulations

Formulation

Percent yield

F1

99.59%

F2

98.34%

F3

97.44%

F4

99.81%

F5

98.76%

 

 

Table No. 3:  Drug content of gel formulations

Formulation code

Drug Content

F1

94.41

F2

97.38

F3

98.24

F4

96.52

F5

95.07

 

 

Table No. 4:  pH of gel formulations

Formulation

PH

F1

6.98

F2

7.01

F3

6.98

F4

6.5

F5

6.79

 

 

Table No. 5: Viscosity of gel formulations

Formulation

Viscosity (cp)

F1

8476

F2

4259

F3

4450

F4

4544

F5

6.79

 

 

Table No. 6: Spredability of gel Formulations

Formulation

Spredability

R1

R2

F1

1.3

1.9

F2

2.1

2.9

F3

19

2.8

F4

1.7

2.3

F5

1.5

2.1

 

 

Table No. 7:  Extrudability of gel Formulations

Formulation

Extrudability

F1

+

F2

+++

F3

+++

F4

++

F5

++

Excellent (+++)

Good (++)

Average (+)

Poor (-)

 

 

Table No. 8:  In Vitro diffusion chart      

Time       

% CDR

F1

F2

F3

F4

F5

0

0

0

0

0

0

30

12.95

16.87

14.88

14.03

13.67

60

39.51

44.39

41.39

40.76

40.05

90

47

48.49

47.95

47.02

46.91

120

56.59

56.01

57.18

56.24

55.74

150

62.84

61.28

63.59

62.31

61.89

180

71.84

72.69

73.26

72.13

71.84

210

80.17

79.37

82.15

81.68

80.86

240

87.27

86.16

89.07

88.19

87.98

270

95.98

94.09

97.03

96.83

96.03

                               

 

                               

Fig: In vitro diffusion for F3 Formulation.

               

                               

CONCLUSION:

Various formulation (F1, F2, F3, F4, F5) were developed by using suitable polymer (carbopol 934p and HPMC). Developed formulations of Itraconazole were evaluated for the physiochemical parameters such as percentage yield, drug content, pH, viscosity, spredability, extrudability, in vitro drug diffusion. Viscosity studies of various formulations revealed that formulation F3 was better compare to others. From among all the developed formulation F3 shows better drug diffusion, did good Rheological properties. pH of the F3 formulation is sufficient enough to treat the skin infections. Results indicated that the concentration of carbopol-934 and HPMC K4M significantly affects drug release and rheological properties of the gels. The viscosity of carbopol-934 gels was very high as compared to HPMC K4M gels but both gels showed decrease in drug release with increase in polymer concentration. Thus, gels can be successfully prepared using carbopol-934 and Hydroxypropyl methylcellulose as gelling agents in the ratio 1:3(carbopol-934 and Hydroxypropyl methylcellulose) suitable for topical application Hence formulation F3 should be further developed for scale-up to industrial production.

 

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Received on 10.08.2018                    Accepted on 15.09.2018

©A&V Publications all right reserved

Research J. Topical and Cosmetic Sci. 9(2): July- Dec. 2018 page 49-52.

DOI: 10.5958/2321-5844.2018.00010.9