The skin is the primary mechanical defense system and act as barrier for penetration of many pharmacological compounds, and it also serves as an ideal site for local and systemic drug delivery. Over the last few decades, the topical route of medication delivery has been increasing popularly despite the limitations of traditional topical medication delivery techniques, such as poor retention and bioavailability. This disadvantage is resolved through intensive research aimed at developing novel topical drug delivery technologies that increase safety, effectiveness, and side effects [1-3]. Skin is the largest organ of the body and contributes about 15% of the total adult body weight and covers an average area of 1.7 m2. The major function of skin is to protect the internal body from the external environment such as temperature, humidity and radiation. The skin also regulates the water content and heat loss from the body. The skin is made up of three sheets of different components an outermost sheet termed as epidermis, a middle sheet is termed as dermis and innermost sheet is termed as hypodermis [4-5]. There are various skin diseases in which the administration of a hydrophobic medication is required, the topical delivery method fails. Other cutting-edge methods include niosomes and liposomes, which are nanosized and may leak due to their vesicular architecture, resulting in less effective trapping [6]. Many excipients are included in each formulation containing active substances. Sometimes more than one formulation can be blended to improve medication delivery emulgel is one of such examples. It is a combination of emulsion and gel. Emulgel is a more recent innovation in novel drug delivery system that is used topically and has the properties of both an emulsion and a gel for dual control release. Emulgel are either w/o or o/w emulsions that have been mixed with a gelling agent to create a gelled state. Emulgel are the most stable and ideal delivery system for hydrophobic drugs. Emulgel have a high rate of patient acceptance. Emulgel, which have two phases—aqueous and non-aqueous can deliver both hydrophilic and lipophilic medicines, when compared to other topical medicines that require excessive rubbing, they are applied to skin appropriately because they are non-greasy [7-8]. The aim of this work was to develop an emulgel formulation of diclofenac potassium, a hydrophobic drug, using Carbopol 940, hydroxypropyl methyl cellulose (HPMC), xanthine as gelling agent and penetration enhancer, i.e. Clove oil. In this research article the influence of different polymeric gelling agent and release along with the rheological studies, spreading coefficient and in vitro release has been studied.

MATERIALS AND METHODS

Materials

Diclofenac potassium, Carbopol 940, HPMC, xanthine was obtained from departmental lab. All other chemicals used were of analytical grade and were used without any further chemical modification.

Methods

The emulgel was prepared using following steps:

1. Emulsion formation
2. Formation of gel base
3. Mixing of emulsion into gel base

Step 1: Emulsion formation

Preparation of aqueous phase: The aqueous phase was prepared by dispersing the calculated amount of tween 20 in purified water and heat separately at 70ºC. Propyl paraben and methyl paraben were used as preservatives and were dissolved in propylene glycol. On the other hand, diclofenac potassium was dissolved in ethanol. Both the mixture was added to the aqueous phase.

Preparation of oil phase:

The oil phase was prepared by dispersing the calculated amount of span 20 in light liquid paraffin and heat separately at 70 ?C.

Mixing of oil phase and aqueous phase:

Afte heating, the oil phase was added to the aqueous phase by continuous stirring until it cool. [9-10]

Step 2: Formation of gel base

1. Preparation of carbopol 940 gel:

The carbopol 940gel was prepared by adding the calculated amount of carbopol 940in the warm water with continuous stirring on a magnetic stirrer at moderate speed. The pH of carbopol 940gel was adjusted by using triethanolamine.

2. Preparation of HPMC gel:

The HPMC gel was prepared by adding a calculated amount of HPMC in warm water with continuous stirring on a magnetic stirrer at moderate speed.

3. Preparation of Xanthine gel:

The xanthine gel was prepared by adding a calculated amount of xanthine in warm water with continuous stirring on a magnetic stirrer at moderate speed.

Step 3: Formation of emulgel

The prepared emulsion was mixed with all the gel base separately with an appropriate ratio with continuous stirring to obtain the emulgel. The prepared emulgel was stored in glass jar with a tight lid [11].

Table 1: Composition of emulgel of diclofenac potassium.

Figure 1: Formulations of emulgel containing various polymer

EVALUATION OF EMULGEL

Visual examination:

In the visual examination, formulations were investigated for the color, phase separation, and homogeneity of emulgel.

Spreadability test:

Spredability is one of the important parameters for topical delivery of formulation. It was performed using a wooden block and glass slide apparatus to determine spreadability. A modified apparatus consisting of two glass slides with sample in between, with the lower side fixed to a wooden block and the upper side attached to a balance by a hook. All of the samples (about 1g) were placed between these two glass slides and pressed together for 5 minutes to expel the air and provide a uniform thickness of gel by placing a suitable weight. The top glass slide of the same size was fixed with ground slide. As a result, a weight (50g) was added to the pan, and the glass slide was pulled with the help of a stirring stick attached to the hook. The time taken by upper glass slide to move over the lower plate by 10 cm was recorded. The spreadability was calculated using the formula below:

S = M× L / T

Where, S=Spreadability in g .cm/s

 M=Mass of gel placed between the two slides

 L=Length of slide (cm)

T=Time taken by the upper slide to detatch (seconds/minutes)

pH determination:

By using a digital pH meter, the pH of each formulation was calculated. The readings of pH will be taken an average of 3 times. [12-13]

Drug content:

Separately, a specific amount (1gm) of each developed formulation was taken and dissolved in 100 ml of phosphate buffer (pH 5.5). The volumetric flasks containing the gel solution were shaken for 2 hours to ensure complete drug solubility. After an appropriate dilution, the solution was filtered and analyzed with UV-spectrophotometer at 282.2 nm.

Stability studies:

The accelerated stability studies were carried out in accordance with the ICH guidelines Q1R2 in order to gain access to the drug and formulation stability for three months. The optimized formulation was stored in screw-capped amber colored glass bottles at 45 ± 5°C and 75±5 % relative humidity. At different time interval till 3 months, samples were analyzed for physical appearance, pH and drug content.

Viscosity:

Viscosity of emulgel was determined by using a Brookfield viscometer with spindle no.04 at 100 RPM. [14-15]

In vitro release study:

By using an eggshell membrane with a receptor compartment (80ml capacity) in vitro release studies were performed. With the help of a thread, the eggshell membrane was fixed at the end of the hollow tube as a donor compartment and beaker present as a receptor compartment. a specified quantity of prepared emulgel was applied on to the surface of the eggshell membrane and eggshell membrane clamped between the donor and receptor chamber. Receptor compartment filled with phosphate buffer solution pH 7.4 to solubilize the drug. On the magnetic stirrer, the whole assembly was placed and the solution was continuously stirred with the help of a magnetic bead. The temperature was maintained at 37±0.5ºC. At suitable interval, 1ml sample was withdrawn and analyzed for drug content spectrophotometrically at 282.2 nm.[16]

RESULTS AND DISCUSSION

Physicochemical properties:

Formulations were investigated for colour, phase separation, pH, spreadibility and compared with marketed formulation, the results shown in Table 2.

Table 2: Physicochemical properties of diclofenac potassium emulgel

Drug content:

For all the diclofenac potassium, drug content analysis was done using the phosphate buffer (pH 7.4) as the medium and the results are given in Table3.

Stability study:

All the formulations of emulgel were found to be stable after different intervals till 3 months at 45±5 ?C and 75±5 % RH. No changes were recorded in parameters like visual appearance, pH, spreadability, and drug content. Syneresis is the main drawback of gel; also, there was no presence of syneresis effect.

Viscosity:

The viscosity of the formulations in which carbopol 940, HPMC, xanthine was used as gelling agent is given below in Table 4

   

In vitro release study: In vitro release study of all the formulations of emulgel was performed using phosphate buffer solution medium at 7.4 pH for 6 hours. After the time interval at 30 min 2ml sample were withdrawn and diluted with PBS 7.4 pH and the absorbance were measured at ?max 282.2 nm by UV spectrophotometer. The in vitro test was performed to ensure the uniform and accurate release of the drug. Good drug permeability was observed among all emulgel formulations. Result revealed that the release of all the emulgel formulations was found to be in the range of 84.45±0.16% to 89.56±0.66% Formulation F1has shown highest cumulative amount of drug release (89.56±0.66%) for up to 6 hours among all the other emulgel formulations and compared with marketed formulation of emulgel indicated that the rate of drug release depended upon the percentage of drug entrapment efficiency. The maximum release was also due to optimum surfactant concentration because at this concentration the surfactant molecule gets associated with the bi-layer resulting in better partitioning of the drug and result in higher drug release from the vesicles. The in vitro drug release profile of all emulgel formulation was shown in Table 5 and Figure 2.

Figure 2: Cumulative% drug release of emulgel formulations

DISCUSSION