topical gel

A Gupta et al. / Drug Invention Today 2010, 2(5),250-253

Drug Invention Today Vol.2.Issue 5.May 2010 250-253

Research Article

Available online throughwww.ditonline.info

*Corresponding author.A GuptaBabu Banarasi Das National Institute of Technologyand Management, Lucknow, IndiaTel.: + 91-0902346846E-mail: [email protected], [email protected]

INTRODUCTION

For topical treatment of dermatological disease as well asskin care, a wide variety of vehicles ranging from solids to semisolidsand liquid preparations is available to clinicians and patients. Withinthe major group of semisolid preparations, the use of transparent gelshas expanded both in cosmetics and in pharmaceutical preparations[1]. A gel is colloid that is typically 99% wt liquid, which is immobilizedby surface tension between it and a macromolecular network of fibersbuilt from a small amount of a gelating substance present [2]. Topicaldrug administration is a localized drug delivery system anywhere inthe body through ophthalmic, rectal, vaginal and skin as topical routes.Skin is one of the most readily accessible organs of human body fortopical administration and main route of topical drug delivery system.Numbers of medicated products are applied to the skin or mucousmembrane that either enhance or restore a fundamental function of askin or pharmacologically alter an action in the underlined tissues.Such products are referred as topical or dermatological product [3].Hydroxypropyl methylcellulose (HPMC), Carbapol 934P, Sodium al-ginate has been used as hydrophilic polymers topically in gel drugdelivery system [4, 5]. A series of grades based on molecular fractions

Formulation and evaluation of topical gel of diclofenac sodium using different polymersA Gupta1*, AK Mishra2, AK Singh1, V Gupta2, P Bansal31Babu Banarasi Das National Institute of Technology and Management, Lucknow, India2 National Institute of Ayurvedic Pharmaceutical Research, CCRAS, Patiala, India3 Baba Farid University of Health Sciences, Faridkot, India

Received on: 15-01-2010; Revised on: 15-03- 2010; Accepted on:15-04-2010

ABSTRACTA wide choice of vehicles ranging from solids to semisolids form has been used for skin care and topical treatment of dermatological disease, High molecularweight water soluble polymers of Hydroxypropyl methylcellulose (HPMC), Carbapol 934P, Sodium alginate that possess very high viscosity, transpar-ency, film forming properties at low concentration, are reported to useful in formation of gel. In the present investigation Diclofenac sodium gels wereprepared for topical drug delivery by using different concentration of HPMC, Sodium alginate, Carbapol 934P, with an objective to increase transparencyand spreadability. From the study it was concluded that HPMC gel containing Diclofenac sodium showed good consistency, homogeneity, spreadability andstability and has wider prospect for topical preparations as compared to Sodium alginate, Carbapol 934P gel containing Diclofenac sodium.

Keywords: Topical drug delivery, Diclofenac sodium, HPMC, Carbapol 934P, Sodium alginate

ISSN: 0975-7619

of these polymers are used at a concentration between 1 to 5% intopical gel formulation. Due to their non greasy properties, they canprovide easily washable film on the skin [4, 6]. HPMC, Carbapol 934P,Sodium alginate polymers of high molecular weight do not penetratethe skin and are non toxic in nature [4, 7].

MATERIAL AND METHODS

Diclofenac sodium, HPMC, Carbapol 934P and Sodium algi-nate were procured from Babu Banarasi Das National Institute ofTechnology and Management, Lucknow, India. All other ingredientsused were of analytical grade.

Procedure of gel preparation

For Formulation F1, F2, F3 1g of diclofenac sodium wasweighed and dissolved in 15ml of glycerin with the help of mild heat(solution A). Weighed quantity of HPMC was added to the 75ml ofdistilled water and stirred until dissolved (solution B). Solution A andB were mixed thoroughly and the final weight was made up to 100g.For Formulation F4, F5, F6 1g of diclofenac sodium was weighed anddissolved in 15ml of glycerin with the help of mild heat (solution A).Weighed quantity of carbapol 934P was added to the 75ml of distilledwater and stirred until dissolved and then neutralized by the 10%NaOH (solution B). Solution A and B were mixed thoroughly and thefinal weight was made upto 100g. For Formulation F7, F8, F9, 1g ofdiclofenac sodium was weighed and dissolved in 15ml of glycerinwith the help of mild heat after that mixed thoroughly methyl paraben

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& propyl paraben (solution A). Weighed quantity of sodium alginatewas added to the 75ml of distilled water and stirred to dissolve thesame (solution B). Solution A and B were mixed thoroughly and thefinal weight was made up to 100g. (Table 1)

Precipitation occurs in some of the batches (F1, F3, F4, F6,F7 andF9) of polymer based gel containing diclofenac sodium whichcould be due to the incompatibility in the system. Hence, these batcheswere discarded and remaining batches (F2, F5 and F8) were consid-ered for further study.

F2 F5 F8

Figure. 1: Photo of Formulated Diclofenac Sodium Gels

EVALUATION OF POLYMER BASED GEL CONTAININGDICLOFENAC SODIUM:

The above formulated polymer based gel containingDiclofenac sodium was subjected to evaluation for the following pa-rameters:

Preformulation studies

Preformulation studies are needed to ensure the develop-ment of a stable as well as therapeutically effective & safe dosageform. It is a stage of development during which characterizes thephysico-chemical properties of the drug substance and it interactionwith various formulation components. (Table 2)

pHThe pH of various gel formulations was determined by us-

ing digital pH meter (Table 3)

Spreadability

It was determined by wooden block and glass slide appara-tus. Weights about 20g were added to the pan and the time werenoted for upper slide (movable) to separate completely from the fixedslides. [8] (Table 3)Spreadability was then calculated by using the formula:

S = M.L / TWhere,S = SpreadabilityM = Weight tide to upper slideL = Length of glass slideT = Time taken to separate the slide completely from each other

Viscosity

Viscosity was determined by using brookfield viscometer.Viscosity measurements were carried out at room temperature (25-27C) using a Brookfield viscometer (Model RVTDV II, BrookfieldEngineering Laboratories, Inc, Stoughton, MA). (Table 3)

Consistency

The measurement of consistency of the prepared gels wasdone by dropping a cone attached to a holding rod from a fix distanceof 10cm in such way that it should fall on the centre of the glass cupfilled with the gel. The penetration by the cone was measured fromthe surface of the gel to the tip of the cone inside the gel. The dis-tance traveled by cone was noted down after 10sec. [9] (Table 3)

Homogeneity

All developed gels were tested for homogeneity by visualinspection after the gels have been set in the container. They weretested for their appearance and presence of any aggregates. (Table 3)

Skin irritation test

Test for irritation was performed on human volunteers. Foreach gel, five volunteers were selected and 1.0g of formulated gel wasapplied on an area of 2 square inch to the back of hand. The volun-teers were observed for lesions or irritation. (Table 3)

Drug content

A specific quantity (100mg) of developed gel and marketedgel were taken and dissolved in 100ml of phosphate buffer of pH 6.8.The volumetric flask containing gel solution was shaken for 2hr onmechanical shaker in order to get complete solubility of drug. Thissolution was filtered and estimated spectrophotometrically at 276nmusing phosphate buffer (pH 6.8) as blank. [10] (Table 3)

Accelerated Stability Studies

All the selected formulations were subjected to a stabilitytesting for three months as per ICH norms at a temperature of 40 2.All selected formulations were analyzed for the change in appear-ance, pH or drug content [11] (Table 4)

Permeability studies [12]

Phosphate buffer of pH 6.8 was used for in vitro release asa receptor medium. The pretreated skin of albino mice was used in frazdiffusion cell. The gel sample was applied on the skin and then fixedin between donor and receptor compartment of diffusion cell. Thereceptor compartment contained phosphate buffer (100ml) of pH 6.8.The temperature of diffusion medium was thermostatically controlledat 37 1 by surrounding water in jacket and the medium was stirredby magnetic stirrer at 500rpm. The sample at predetermined intervals


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Batch Drug Polymer (g) 10% Glycerin Methyl Propyl DistilledNo (g) HPMC Carbapol Sodium

(g) 934P (g) alginate (g) NaOH (ml) paraben (ml) paraben (ml) Water (ml)

F1 1 3 - - - 15 - - Upto100F2 1 3.5 - - - 15 - - Upto100F3 1 4 - - - 15 - - Upto100F4 1 - 0.25 - q.s. 15 - - Upto100F5 1 - 0.5 - q.s. 15 - - Upto100F6 1 - 0.75 - q.s. 15 - - Upto100F7 1 - - 8 15 0.1 0.05 Upto100F8 1 - - 8 15 0.2 0.1 Upto100F9 1 - - 8 15 0.3 0.15 Upto100

Table 1: Composition and concentration of Diclofenac sodium gel

Identification Solubility Dissolution Partition Melting

Methanol Ethanol Water Ether,(95%) & GAA chloroform constant (PKa) coefficient point 0C

Drug + 1 ml of 0.4% w/v soln. ++++ +++ ++ + 4 3.5 280

++++ Very soluble, +++ moderately soluble, ++ slightly soluble, + practically soluble

Table 3: Values of evaluation parameters of developed gel

Batch pH Spreadability Viscosity Consistency Homogeneity Skin Drug

No (g.cm/sec) (dyns/cm 2) (60 sec) irritation Content (%)F2 7.4 5.6 0.94*10-3 6 mm Very Good Nil 99.81F5 6.8 3.8 1.6*10-3 6 mm Good Nil 99.75F8 7.1 3.9 1.7*10-3 5 mm Good Nil 99.96

Table 4: Stability study of various formulated gel

Serial Batches Months Appearance pH DrugNo Content (%)1 F2 0 Clear 7.4 99.81

1 Clear 7.4 98.272 Clear 7.3 97.543 Clear 7.3 96.91

2 F5 0 Clear 6.8 99.751 Clear 6.8 98.872 Clear 6.7 96.053 Clear 6.6 95.33

3 F8 0 Clear 7.1 99.961 Clear 7.1 97.122 Clear 7.1 96.433 Clear 7.0 95.65

Table 5: Permeability Studies of formulated gels

Sr. Time Medium pH %Drug releaseNo Interval Batch F2 Batch F5 Batch F8 (min)

1 30 6.8 38.54 44.61 56.002 60 6.8 64.78 71.35 75.413 90 6.8 81.23 84.38 90.114 120 6.8 96.87 97.72 98.54

Table 2: Preformulation study of drug

in methanol + 1 ml. nitricacid produced red colour

were withdrawn and replaced by equal volume of fresh fluid. Thesamples withdrawn were spectrophotometrically estimated at 276nmagainst their respective blank. (Table 5)

RESULTS AND DISCUSSION

In the Preformulation studies the identification of drug by

chemical test, producing red colour on reaction with methanol andnitric acid. The melting point of drug was found to be 2800C. Thesolubility of drug was very soluble in methanol, soluble in ethanol,slightly soluble in water, and practically soluble in ether. The partitioncoefficient and dissolution constant were 3.5 and 4 respectively. ThepH values of all developed (F2, F5, and F8) were 7.4, 6.8 and 7.1respectively. The values of spreadability indicate that the gel is easilyspreadable by small amount of shear. Spreadability of formulated gels(F2, F5, and F8) were 5.6, 3.8 and 3.9 g cm/sec. Hence spreadability ofF2 formulation was good as compared to F5 and F8 formulation. Theconsistency reflects the capacity of the gel, to get ejected in uniformand desired quantity when the tube is squeezed. Hence, the consis-tency of F2 formulation was better as compared with F8 formulation.All developed gel showed good homogeneity with absence of lumps.The formulated F2 preparation was much clear and transparent ascompared to F5 and F8 formulation as shown in figure 1. The skinirritation studies of developed gel were carried out on human volun-teers and that confirmed the absence of any irritation on the appliedsurface in all formulations. During the accelerated stability studiesthe appearance was clear and no significant variation in pH was ob-served and drug content is 96.91% in F2 formulation after 3 monthswhere as drug content in F5 and F8 was 95.33 and 95.65 respectively.In vitro Permeability study showed that permeation of formulations(F2, F5 and F8) was comparable with each other.

CONCLUSION

It was observed that hydroxypropyl methylcellulose (HPMC)gel containing Diclofenac sodium (F2) produced better spreadability

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Source of support: Nil, Conflict of interest: None Declared

and consistency as compared to carbapol 934P gel (F5) and sodiumalginate gel (F8) formulation. The developed F2 gel showed goodhomogeneity, no skin irritation, good stability and in vitro permeabil-ity. The HPMC forms water washable gel because of its water solubil-ity and has wider prospects to be used as a topical drug deliverysystem.

REFERENCES

1. Provost C, Transparent oil-water gels; a review, Int J Cosmet Sci., 8, 1986, 233-247.2. Ferry John D, Viscoelastic Properties of Polymers, New York: Wiley, 1980.3. Rashmi MS, Topical Gel: A Review, 6(3), 2008, 244-249.4. Shivhare UD, Jain KB, Mathur VB, Bhusari KP, Roy AA, Formulation development

and evaluation of Diclofenac sodium gel using water soluble polyacrylamide poly-mer, Digest Journal of Nanomaterials and Biostructures, 4(2), 2009, 285 290.

5. Golinkin HS, Process for fracturing well formations using aqueous gels, 1979, USPatent No. US 4137182.

6. Fried JR, Polymer Science and Technology. Prentice-Hall, New Jersey, 1998.7. Allan LV, Nicholas J, Ansel HC, Pharmaceutical dosage forms and drug delivery

system, 8 th edition, B.I. publications pvt. Ltd., 421-427.8. Gupta GD, Gound RS, Release rate of nimesulide from different gellants, Indian J

Pharm Sci., 61, 1999, 229-234.9. William L, Remington: The Science and Practice of Pharmacy, 20th edition. Mack

Publishing Company. Easton, PA, 2000.10. Sera UV, Ramana MV, In vitro skin absorption and drug release a comparison of four

commercial hydrophilic gel preparations for topical use, The Indian Pharmacist, 73,2006, 356-360.

11. ICH Harmonized Tripartite Guidelines, Stability Testing of New Drug Substancesand Products, ICH Committee, 8, 2003.

12. Sahoo SK, Samal AR, Estimation and evaluation of secnidazole. The Indian Pharma-cist, 5(46), 2006, 73.

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