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Preparation and characterization of a Unani Transdermal antiemetic Emulgel: A novel approach | Advance Pharmaceutical Journal

Research Articles

2016  |  Vol: 1(4)  |  Issue: 4 (September- October)
Preparation and characterization of a Unani Transdermal antiemetic Emulgel: A novel approach

Mohd Nauman Saleem1, Mohammad Idris2

1Research Associate, Central Council for Research in Unani Medicine, New Delhi

2Professor and HOD, Departments of Ilmul Advia and Ilmul Saidla, A & U Tibbia College, Karol Bagh, New Delhi

 

*Corresponding Author

Mohd Nauman Saleem

Central Council for Research in Unani Medicine, New Delhi

Phone No.: 91-9871505359


Abstract

Objective: Emesis is an emergent condition which requires urgent medical attention. Since oral route of drug administration is often not suited in this condition and due to certain limitations of conventional parenteral therapy an alternate transdermal route was explored. A novel drug delivery dosage form was designed i.e. an emulgel. The aim of the present study was to formulate and evaluate a Unani transdermal antiemetic emulgel (UTAE). Materials and methods: The ingredients of emulgel formulation were Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis) and Sirka (Vinegar). After the preformulation phase, a suitable emulsion and gel base was prepared and optimized. The emulgel was prepared by a previously reported method and was evaluated for organoleptic characteristics and other physico-chemical properties such as pH, viscosity, spreadability, extrudability, drug content and stability. The in-vitro permeation study of UTAE was carried out using Franz Diffusion Cell and egg shell membrane was used as the barrier membrane. Results and conclusion: Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 1°C. The in-vitro permeation study of UTAE indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release after 24 hours was 73.31 %. The study leads to a novel exploration in Unani pharmaceutics. A clinical study should also be envisaged to evaluate therapeutic efficacy of the prepared emulgel.

Keywords: Unani emulgel, Antiemetic emulgel, Transdermal delivery


Introduction

Emesis or vomiting is an emergent condition in which the upper gastro-intestinal tract rids itself of its contents by expelling them out through the mouth (Guyton and Hall, 2007). The oral route of drug administration is often not suited in this condition. In such cases parenteral therapy is preferred, but there is no such provision in Unani system of medicine. Moreover, since it is an invasive technique, so in conventional system also it is nothing short in terms of poor patient compliance, availability and safety. Thus, an alternate transdermal route was explored for drug administration (Saleem and Idris, 2015). Inter alia the main advantage of transdermal drug delivery system is that it bypass the first pass hepatic metabolism (Pant et al., 2015). Though the concept of transdermal drug delivery appears to be new in conventional pharmacology but the Unani classical literature has ample evidence of it. The Unani physicians had devised various topical formulations in the form of zimad (paste), marham (ointment), tila (liniment), roghan (oil), etc for localized as well as systemic therapy (Saleem, 2015). But these forms are usually very sticky causing uneasiness to the patients when applied. Moreover, they have less spreading coefficient and need to be rubbed thoroughly and also exhibit stability problems (Khunt et al., 2012). To overcome such shortcomings a novel drug delivery dosage form was envisaged i.e. an emulgel. When gels and emulsions are used in combined form, the dosage form is known as Emulgel (Khullar et al., 2011). It is a unique dosage form which has been developed for a number of drugs in recent years, intended for topical or systemic action. It is prepared by mixing an oil-in-water type or water-in-oil type emulsion with a gelling agent. Incorporation of an emulsion into a gel base enhances its stability (Prajapati et al., 2013). Transdermal emulgels have several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, water soluble, longer shelf life, bio-friendly and pleasing appearance (Jain et al., 2010). Furthermore, the transdermal emulgel have high patient compliance.

The aim of the present study was to formulate and evaluate a Unani transdermal antiemetic emulgel (UTAE). The formulation was based on four ingredients, namely Khardal (Brassica nigra), Zanjabeel (Zingiber officinale), Podina (Mentha arvensis) and Sirka (Vinegar). Khardal was the main ingredient of the formulation and Sirka was used as an excepient (Kabiruddin, ynm). Zanjabeel and Podina were added to the formulation as these drugs act as permeation enhancers (Singla et al., 2011; Wungsintaweekul et al., 2004), and at the same time they produce suitable synergistic effect too (Khan, 1892; Tate, 1997; Vishwakarma, 2002).

Materials and methods

Materials

The ingredients of the formulation were procured from the open market. The impurities from herbal drugs were inspected with naked eyes and removed. Samples of all the herbal drugs were identified by the experts of National Institute of Science Communication and Information Resources (NISCAIR), CSIR, New Delhi. All other chemicals and reagents used were of analytical grade.

Methods

Formulation of UTAE

Extraction of Volatile Oils of Khardal, Zanjabeel, and Podina: The volatile oils from Khardal seeds, Zanjabeel rhizomes, and Podina leaves were extracted using Clevenger apparatus (Kumar, 2010).

Preparation of Calibration Curve for Khardal Oil: A standard calibration curve for volatile oil of Khardal was prepared by dilution method. The absorbances were determined spectrophotometrically at 𝜆max of 304nm (Saleem and Idris, 2016).

Screening and selection of surfactant and co-surfactant: Acacia gum, Tween 20 and Tween 80 were the different surfactants screened and ethanol was selected as the co-surfactant due to its wider acceptance.

Optimization and preparation of emulsion: An oil-in water (o/w) emulsion was prepared using different surfactants. The oil phase was made by taking 75% of Khardal oil and 25% of mixture of equal parts of Zanjabeel oil and Podina oil. The aqueous phase used was 5% and 10% solution of Sirka. Emulsions were prepared in different ratios of oil phase: surfactant: aqueous phase (O: S: A) and kept at room temperature for one month to check their stability.

Optimization and preparation of gel: The gel base was prepared by using carbopol-940 as gelling agent. Different concentrations of gel base i.e. 1%, 1.5%, 2%, 2.5% and 3% (w/v), respectively, were prepared and optimized.

Preparation of emulgel: After optimization and selection of suitable gel base, the stable emulsion was incorporated into the gel base. The emulsion was incorporated in gel base in different percentage, i.e. 1%, 1.5%, 2%, 2.5% and 3% (w/w), respectively, and the emulgel which remained stable was finally selected as UTAE and evaluated.

Evaluation of UTAE

Organoleptic characteristics: The prepared UTAE was physically inspected for its appearance, colour, homogeneity, consistency, grittiness and phase separation.

pH measurement: The pH of prepared UTAE was determined by using pH meter. 1 gm and 10 gm of emulgel was dissolved in 100 ml of distilled water separately, i.e. 1% and 10% solution of formulation was prepared and was kept aside for 2 hrs. Then, the measurement of pH was done six times and average values were calculated (Haneefa et al., 2014).

Viscosity: The viscosity of UTAE was determined using Brookfield viscometer (Haneefa et al., 2014).

Spreadability: Two sets of glass slides of standard dimensions were taken. The UTAE was placed over one of the slides. The other slide was placed on the top of UTAE, such that it was sandwiched between the two slides in an area occupied by a distance of 7.5 cm along the slide. 100gm weight was placed upon the upper slide so that the UTAE between the two slides was pressed uniformly to form a thin layer. The weight was removed and the excess of UTAE adhering to the slides was scrapped off. The two slides in position were fixed to a stand without slightest disturbance and in such a way that only the upper slide to slip off freely by the force of weight tied to it. A 20 gm weight was tied to the upper slide carefully. The time taken for the upper slide to travel the distance of 7.5 cm and separated away from the lower slide under the influence of the weight was noted (Oswal and Naik, 2014). The experiment was repeated three times and the mean time taken was calculated by using the following formula:

S = m × l / t

where,

S  is the Spreadability

m  is the weight tied to the upper slide (20gm)

l  is the length of the glass (7.5 cm)

t  is the time taken in seconds

Extrudability: The extrudability test was carried out using hardness tester. A 15 gm of UTAE was filled in aluminium tube. The plunger was adjusted to hold the tube properly. The pressure of 1 kg/ cm2 was applied for 30 sec. The quantity of UTAE extruded was weighed. The procedure was repeated at 3 equidistant places of the tube (Oswal and Naik, 2014).

Drug content: The drug concentration in UTAE was measured by dissolving known quantity of UTAE in solvent (ethanol). The absorbance was measured after suitable dilution using UV-Visible spectrophotometer (Oswal and Naik, 2014).

Stability study: The stability study of prepared UTAE was done at room temperature for 1 month, and the formulation was finally evaluated for appearance, pH and drug content (Khunt et al., 2012).

In-vitro permeation study of UTAE: The in-vitro permeation study of the prepared UTAE was carried out through Franz Diffusion Cell and egg shell membrane was used as the barrier membrane because the egg shell membrane resembles human stratum corneum as it consists mainly of keratin (Haigh and Smith, 1994). The membrane was prepared before use according to a previously reported method (Shah et al., 2010). The water in the outer jacket of the cell was warmed and set at 37±1°C throughout the experiments to provide a skin surface temperature. In the study 250mg sample of UTAE was taken and applied over the mounted membrane in diffusion cell. After application of drug, the samples were withdrawn from the receptor compartment at regulated intervals. One ml of the receptor solution was collected as sample each time and simultaneously one ml of phosphate buffer solution was added back to the receptor cell for maintaining the same initial volume of the receptor cell solution. The sampling schedule was at 0, 15, 30 and 60 minutes for the first hour of release and then it was at every hour interval till 6th hour of release. After that the whole system was kept in its normal position for overnight and then next day reading was taken at 24th hour. The collected samples were analysed using UV-Vis spectrophotometer (Shah et al., 2010).

Results and discussion

There are a number of antiemetic formulations mentioned in Unani classical literature which are topically applied over the intact skin to achieve desired therapeutic action. So a novel dosage form was designed in the form of UTAE incorporating Unani drug components and pharmaceutically evaluated on the basis of standard parameters. To formulate UTAE, firstly volatile oils from different ingredients were extracted. The rationale behind extraction of volatile oils is that according to literature volatile oil form is best suited for transdermal drug delivery as it can penetrate more through the skin and the dosage is also reduced. Also in this case volatile oil contained the active constituents of the respective drugs.

Initially a standard calibration curve for volatile oil of Khardal was prepared as shown in figure 1. Using the concentration and absorbance data given in table 1, a standard plot was obtained.

Table 1. Data for volatile oil of Khardal

S. No.

Concentration (µg)

Absorbance (nm)

1.

15.625

0.077

2.

31.25

0.112

3.

62.5

0.171

4.

125

0.285

5.

250

0.501

6.

500

0.932

Figure 1. Calibration curve for volatile oil of Khardal

 

 

Formulation of UTAE

Selection of surfactant and co-surfactant: After screening tween 80 was selected as surfactant and the co-surfactant selected was ethanol.

Optimization and preparation of emulsion: Ten versions of the emulsions were prepared in different ratios using 5% and 10% vinegar solution as aqueous phase and were analyzed for their stability as given in table 2 and table 3, respectively. All the emulsions prepared with 10% vinegar solution were found to be unstable. Whereas, in the emulsions prepared with 5% vinegar solution, only the emulsions in percentage ratios of 10%:50%:40% and 15%:50%:35% were found to be stable. Therefore, the emulsion with higher concentration of oil was selected i.e. in ratio of 15%:50%:35%.

Table 2. Preparation of emulsion with 5% vinegar solution as aqueous phase

S. No.

Different Percentage Ratios of O: S: A

Result

1.

10%: 50%: 40%

Stable

2.

15%: 50%: 35%

Stable

3.

20%: 50%: 30%

Creaming

4.

25%: 50%: 25%

Creaming

5.

30%: 40%: 30%

Phase Separation

Table 3. Preparation of emulsion with 10% vinegar solution as aqueous phase

S. No.

Different Percentage Ratios of O: S: A

Result

1.

10%: 50%: 40%

Creaming

2.

15%: 50%: 35%

Creaming

3.

20%: 50%: 30%

Creaming

4.

25%: 50%: 25%

Phase Separation

5.

30%: 40%: 30%

Phase Separation

Optimization and preparation of gel base: Five different versions of gel bases were prepared using carbopol-940 and optimization of gel was done on the basis of physical stability. The results of gel optimization are given in table 4. The gel prepared with 3% gelling agent was found best in consistency, so it was selected for incorporation of emulsion.

Table 4. Results of different gel base prepared

S. No.

Percentage of Gelling Agent

Result

1.

1%

Free flowing consistency

2.

1.5%

Very low viscosity

3.

2%

Very low viscosity

4.

2.5%

Gel consistency less viscous

5.

3%

Gel consistency good

Preparation of emulgel: The selected emulsion was incorporated in gel base in different percentages, i.e. 1%, 1.5%, 2%, 2.5% and 3% (w/w), respectively as given in table 5. The emulgel in which maximum amount of emulsion could be incorporated without any phase separation was selected. Therefore, the emulgel of 2.5% (w/w) drug was finally selected as UTAE and further evaluation was carried out.

Table 5. Results of different emulgels prepared

S. No.

Percentage of drug (emulsion)

Result

1.

1%

Stable

2.

1.5%

Stable

3.

2%

Stable

4.

2.5%

Stable

5.

3%

Phase separation

Evaluation of UTAE

Organoleptic characteristics: The prepared UTAE was a homogenous, viscous, white creamy preparation showing no signs of grittiness or phase separation as shown in figure 2.

Figure 2. Sample of prepared UTAE

 

 

 

pH measurement: The mean pH of 1% and 10% solutions of prepared UTAE were 6.46 ± 0.05 and 5.90 ± 0.04, respectively as given in table 6.

Table 6. pH of UTAE

S. No.

pH (1%)

pH (10%)

1.

6.53

5.96

2.

6.44

5.89

3.

6.48

5.91

4.

6.39

5.85

5.

6.49

5.93

6.

6.44

5.88

Mean ± SD

6.46 ± 0.05

5.90 ± 0.04

Viscosity: The mean viscosity of prepared UTAE was 5.93 × 104 ± 0.15 cps as given in table 7.

Table 7. Viscosity of UTAE

S. No.

Viscosity (cps)

1.

5.8 × 104

2.

6.1 × 104

3.

5.9 × 104

Mean ± SD

5.93 × 104 ± 0.15

Spreadability: The mean spreadability of prepared UTAE was 30.07 ± 2.23 g.cm/ sec as given in table 8.

Table 8. Spreadability of UTAE

S. No.

Spreadability (g.cm/sec)

1.

32.6

2.

29.2

3.

28.4

Mean ± SD

30.07 ± 2.23

Extrudability: The mean extrudability of prepared UTAE was 0.89 ± 0.04 gm as given in table 9.

Table 9. Extrudability of UTAE

S. No.

Extrudability (gm)

1.

0.92

2.

0.85

3.

0.89

Mean ± SD

0.89 ± 0.04

Drug content: The mean drug content of the prepared UTAE was 25.67 ± 0.76 mg per 100 grams as given in table 10.

Table 10. Drug content of UTAE

S. No.

Drug content (mg)

1.

25

2.

26.5

3.

25.5

Mean ± SD

25.67 ± 0.76

Stability study: The stability study of prepared UTAE was done at room temperature for 1 month, and formulation was finally evaluated for appearance, pH and drug content as given in table 11.

Table 11. Stability study of UTAE

S. No.

Day

Appearance

pH (1%)

Drug content (mg)

1.

0

White

6.46

25.6

2.

15

White

6.42

25.5

3.

30

White

6.35

25.2

In-vitro permeation study of UTAE: The in-vitro permeation study of the prepared UTAE indicated a time dependent increase throughout the study as shown in figure 3. The release was rapid during first hour which slowed down as the experiment proceeded. The amount of drug release was 19.95% in 15 minutes which further increased to 25.48% in 30 minutes and reached to 31.07% in one hour. The cumulative drug release gradually increased and reached to 50.34% in 6 hours. Finally, at the end of experiment, the cumulative drug release reached to a significant level, i.e. 73.31% in 24 hours, as given in table 12.

Table 12. In-vitro permeation study of UTAE

S. No.

Time (hours)

Concentration (µl/ml)

% CDR

1.

0

0

0

2.

0.25

1.995

19.95

3.

0.5

2.548

25.48

4.

1

3.107

31.07

5.

2

3.667

36.67

6.

3

4.102

41.02

7.

4

4.475

44.75

8.

5

4.754

47.54

9.

6

5.034

50.34

10.

24

7.331

73.31

Figure 3. In-vitro permeation study of UTAE

 

 

Conclusion

In the current pharmaceutical scenario, specifically in Unani system of medicine, there is a serious need to envisage studies on dosage form designing and development. Accordingly, an effort was made to formulate and evaluate a novel drug delivery dosage form i.e. a Unani transdermal antiemetic emulgel (UTAE) for a very common clinical condition. The UTAE prepared was found to be physico-chemically stable and showed no signs of skin irritation. Significant data has been generated through this study leading to a novel exploration in Unani pharmaceutics. Furthermore, clinical studies to evaluate the therapeutic efficacy of the prepared UTAE should also be envisaged.

Acknowledgement

I gratefully acknowledge to the Director General, Central Council for Research in Unani Medicine (CCRUM) for his skillful guidance and support. I would also like to acknowledge the faculty of Post Graduate Department of Ilmul Saidla, A & U Tibbia College, Karol Bagh, New Delhi, for their valuable cooperation.

Conflict of Interest

Authors have no conflict of interest to declare.

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