1. INTRODUCTION:

Ketofenac is an effective non-steroidal anti-inflammatory drug and used as an anti-inflammatory and analgesic agent. Majorly it is available in the form of tablets and gel. Most of the preparations are used for the local properties at the site of their application by the quality of drug penetration into the fundamental layers of skin or mucous membranes¹. Some accidental drug absorption may occur, it is of sub-therapeutic quantities and generally of minor concern. Gels are a relatively newer class of dosage form created by the entrapment of large amounts of aqueous or hydroalcoholic liquid in a network of colloidal solid particles, which may consist of inorganic substances, such as aluminum salts or organic polymers of natural or synthetic origin². They have a higher aqueous component that allows greater dissolution of drugs, and also allows easy movement of the drug through a vehicle that is essentially a liquid, compared with the ointment or cream base³. These are greater in terms of use and patient acceptability.

Despite the many merits of gel, a major limitation is in the delivery of hydrophobic drugs. So to overcome this limitation, emulgels are prepared and used so that even a hydrophobic therapeutic moiety can enjoy the unique properties of gels. When gels and emulsions are used in combined form the dosage forms are referred to as EMULGELS⁴. In recent years, there has been great interest in the use of novel polymers with complex functions as emulsifiers and thickeners because the gelling capacity of these compounds allows the formulation of stable emulsions and creams by decreasing surface and interfacial tension and at the same time increasing the viscosity of the aqueous phase⁵. Emulgels for dermatological use have several favourable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, long shelf life, bio-friendly, transparent, and pleasing appearance⁶.

This work aimed to develop an emulgel formulation of ketoprofen, a hydrophobic drug, using Carbopo l 940 as a gelling agent and two types of penetration enhancer, i.e., Clove oil and Mentha oil. The influence of gelling agents and penetration enhancers was investigated. The spreading coefficient studies, rheological studies, and ex vivo release studies of the prepared emulgels were also evaluated.

2. MATERIALS AND METHODS:

2.1. Materials:

Ketofanac was obtained as a gift sample from USV Pvt. Ltd. Mumbai, and Carbopol 940 was obtained from our reputed college by the hand of respected DR. Sarode, sir. Dialysis membrane (Wistar male rat skin) was obtained from the Government college of Pharmacy Aurangabad. All other chemicals used were of analytical grade.

2.2. Preparation of emulgel:

Different formulations were prepared using varying amounts of gelling agents and diffusion enhancers. The method only varied in the process of making gel in different formulations. The preparation of emulsion was the same in all the formulations. The gel phase in the formulations was prepared by dispersing Carbopol 940 in purified water with constant stirring at a reasonable speed using a magnetic stirrer, then the pH was adjusted to 6–6.5 using tri-ethanol amine (TEA). The oil phase of the emulsion was prepared by dissolving span 20 in light liquid paraffin while the aqueous phase was prepared by dissolving tween 20 in purified water. Methyl and propyl parabens were dissolved in propylene glycol whereas Ketofanac was dissolved in ethanol, and both solutions were mixed with the aqueous phase. Clove oil and Mentha oil were mixed in the oil phase. Both the oily and aqueous phases were separately heated to 70– 80°C, and then the oily phase was added to the aqueous phase with continuous stirring until it got cooled to room temperature. The obtained emulsion was mixed with the gel in 1:1 ratio with moderate stirring to obtain the emulgel (7). The composition of different formulations has been summarised in Table no.1

Table No.1: Formulation table

Sr. No.	Ingredients	F1	F2	F3	F4
1	Ketofanac	1%	1%	1%	1%
2	Carbapol 940	1%	1%	1%	1%
3	Liquid paraffin	7.5%	7.5%	7.5%	7.5%
4	Tween 20	0.5%	0.5%	0.5%	0.5%
5	Span 20	1%	1%	1%	1%
6	Propylene glycol	5%	5%	5%	5%
7	Ethanol	2.5%	2.5%	2.5%	2.5%
8	Methyl parabene	0.03%	0.03%	0.03%	0.03%
9	Ethyl parabene	0.01%	0.01%	0.01%	0.01%
10	Clove oil	-	-	8%	10%
11	Mentha oil	4%	6%	-	-
12	Water	q.s.	q.s.	q.s.	q.s.

3. EVALUATION OF EMULGEL:

3.1 Melting Point Determination:

The melting point of Ketofenac was determined by using the open capillary tube method.⁸

3.2 Physical appearance:

The prepared Emulgel formulations were examined visually for their pH, color, homogeneity, consistency, grittiness, and phase separation.⁹

3.3 Determination of pH:

The pH values of 1% aqueous solutions of the emulgels were measured by a pH meter.¹⁰

3.4 Rheological Study:

The viscosity of the different emulgel formulations was determined at 250 using a Brookfield viscometer equipped with spindle number 64, and the viscosities were recorded at different rotational speeds of 10, 20, 50, and 100 RPM.¹¹

3.5 Spreadability:

The Spreadability of the formulation was determined by an apparatus suggested by¹² which was suitably modified in the laboratory and used for the study. It consists of a wooden block, which was provided by a pulley at one end. A rectangular ground glass plate was fixed on this block. An excess of gel (about 1g) under the study was placed on this ground plate. The gel was then sandwiched between this plate and another glass plate having the dimension of a fixed ground plate and provided with the hook. A 1kg weight was placed on the top of two plates for 5 minutes to expel air and to provide a uniform film of the gel between the plates. An excess of gel was scrapped off from the edges. The top plate was then subjected to a pull of 10g. with the help of string attached to the hook and the time (second) required by the top plate to cover a distance of 5 cm was noted.¹³

3.6 Ex vivo drug release study:

The ex vivo drug release study of selected formulations (F2 and F4) was carried out in a modified Franz diffusion cell, using Wistar male rat skin. A section of skin was cut and placed in the space between the donor and receptor compartment of the FD cell, keeping the dorsal side upward. Phosphate buffer pH 7.4 was used as dissolution media. The temperature of the cell was maintained constant at 32°C by circulating water jacket. This whole assembly was kept on a magnetic stirrer and the solution was stirred continuously using a magnetic bead. A similar blank set was run simultaneously. The samples were withdrawn at suitable time intervals and replaced with equal amounts of fresh dissolution media¹⁴. Samples were analyzed spectrophotometrically at 285nm.

4. RESULTS AND DISCUSSION:

4.1. Melting point determination:

The melting point was determined using the capillary method and it was found to be as per the following table 2: Melting point determination.

Table 2: Melting point determination.

Sr. No.	Formulation	Physical constants
1.	F1	141°C
2.	F2	140°C
3.	F3	132°C
4.	F4	135°C

4.2. Physical characterization:

Emulgels were white viscous creamy preparation with a smooth homogeneous appearance and characteristic odour. Results have been discussed in Table 3.

Table 3: Physical characterization

Sr. No.	Formulation	Color	Homogeneity	Consistency	Phase separation
1.	F1	White	Excellent	Excellent	None
2.	F2	White	Excellent	Excellent	None
3.	F3	White	Excellent	Excellent	None
4.	F4	White	Excellent	Excellent	None

4.3. Determination of pH:

pH values of all prepared formulations ranged from 5.5 to 6.5 near skin pH i.e., 5.5. Results have been discussed in Table 4.

Table 4: Determination of pH

Sr. No.	Formulation	pH
1.	F1	5.61 ± 0.34
2.	F2	5.63± 0.82
3.	F3	6.34± 0.26
4.	F4	6.54± 0.35

4.4. Rheological Study:

The viscosity of all the formulations is shown in Table 5: Rheological Study

Table 5: Rheological Study

Sr. No.	Formulation	Viscosity (CPS)
1.	F1	11200
2.	F2	12500
3.	F3	9400
4.	F4	9200

4.5 Spreadability:

This is an important criterion for an Emulgel is that it should possess good spreadability. Spreadability is a term expressed to denote the extent of area on which the gel readily spreads on application to the skin¹⁵.

The spreadability of various formulations from F1-F4 was mentioned in Table 6: Spreadability determination. It shows that the F2 formulation shows a higher spreading coefficient as compared to other formulations.

Table 6: Spreadability determination

Sr. No.	Formulation	Spreadability (g.cm/sec)
1.	F1	12.385± 1.04
2.	F2	12.543± 1.08
3.	F3	12.084± 1.34
4.	F4	11.875± 1.17

4.6. Ex vivo drug release study:

Table 7: Ex vivo drug release study

Sr. No.	Time (min)	F1 (% drug release)	F2 (% drug release)	F3 (% drug release)	F4 (% drug release)
1.	0	0	0	0	0
2.	5	8.90	9.05	8.80	7.79
3.	10	12.52	15.76	14.31	13.31
4.	15	20.46	26.09	25.37	25.80
5.	20	24.70	32.03	33.76	30.09
6.	30	44.60	44.56	48.04	41.64
7.	60	62.23	63.48	66.25	61.25
8.	120	95.97	99.30	99.02	98.53

5. FINAL EVALUATION TABLE:

Table 8: Final evaluation table

Sr. No.	Formula-tion	Physical constants	pH	Viscosity (CPS)	Spreadibility (g.cm/sec)	% drug release
1.	F1	141°C	5.61 ±0.34	11200	2.385± 1.04	95.97
2.	F2	140°C	5.63± 0.82	13500	2.543± 1.08	99.30
3.	F3	132°C	6.34± 0.26	9400	2.084± 1.34	99.02
4.	F4	135°C	6.54± 0.35	9200	1.875± 1.17	98.53

6. CONCLUSION:

The present work aimed to formulate and evaluate an emulgel containing ketoprofen. Emulgel is one of the current technologies in the Novel Drug Delivery System used for twin control release of emulsion and gel for topical use. Topical drug delivery is generally used to communicate better patient compliance. Emulgel is found to help enhance spreadability, adhesion, and viscosity and hence, this novel drug delivery becomes prevalent. Moreover, they will become a resolution for loading hydrophobic drugs in water-soluble gel bases for long-term stability. The stability of the emulsion is increased when it is incorporated into the gel. The rationale of the current study was to raise the penetration of drugs into the skin. The formulations were evaluated for spreading coefficient studies, rheological studies, and ex vivo release studies. From the Ex vivo studies, formulation F2 showed a maximum release of 99.30% in 120 min. So Ketofenac Emulgel can be used as an anti-inflammatory analgesic agent for topical drug delivery.

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Received on 29.11.2023 Modified on 23.12.2023

Asian J. Pharm. Tech. 2024; 14(1):9-12.

DOI: 10.52711/2231-5713.2024.00003