224| p a g e international standard serial number …. rpa15162363015.pdfemulgel have emerged as one...

224| P a g e International Standard Serial Number (ISSN): 2319-8141

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International Journal of Universal Pharmacy and Bio Sciences 5(4): July-August 2016

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 2.96***

ICV 5.13***

Pharmaceutical Sciences RESEARCH ARTICLE …………!!!

DEVELOPMENT AND CHARACTERIZATION OF MINOXIDIL

EMULGEL FOR TOPICAL DRUG DELIVERY

Shivam Rao*, Ankush Matlonia, Nimrata Seth, Naresh Singh Gill

Department of Pharmaceutics, Rayat Institute of Pharmacy, Railmajra, Ropar, Punjab, India.

KEYWORDS:

Emulgel, Extrudability,

Spreadability,

Rheological properties.

For Correspondence:

Shivam Rao*

Address:

Department of

Pharmaceutics, Rayat

Institute of Pharmacy,

Railmajra, Ropar, Punjab,

India.

ABSTRACT

Emulgel have emerged as one of the most interesting topical delivery

system as it has dual release control system i.e. gel and emulsion. They

have several favourable properties such as being thixotropic, greaseless,

easily spreadable, easily removable, emollient, non staining, long shelf

life bio-friendly, transparent and pleasing appearance. The objective of

the present study was to prepared emulgel of Minoxidil, using Carbopol

940 and Carbopol 934 as a gelling agent. The formulations were

evaluated for pH determination, rheological studies, spreading coefficient

studies, extrudability studies, in vitro drug release and stability study.

The entire tests were founded to be best fitted within the limits. The

stability studies of formulation (F6) at 250C found to negligibly changed

after storage at specified conditions, formulation F6 containing 1%

carbopol-940 was selected as best formulation.

225 | P a g e International Standard Serial Number (ISSN): 2319-8141


1. INTRODUCTION:

Androgenetic alopecia occurs in both men and women and is characterized by the progressive loss

of hair from the scalp in a defined pattern. Alopecia means hair loss which is the most common

problem of modern societies, which create much economical and psychological effect; affecting

about 70% males and 30% females.[1]

Recently, a great effort has been made to treat hair loss or

alopecia. One of the most common types of alopecia is androgenic alopecia and alopecia

areata. Alopecia generally causes absence of hair from skin areas from where it is normally present

particularly from the scalp and may also affects other part of the body.[2]

Minoxidil is 2, 4-diamino-6- piperidinopyrimidine-3-oxide, soluble in water to the extent of

approximately 0.35mg/ml, is more readily soluble in propylene glycol or ethanol, and is nearly

insoluble in acetone, chloroform.[3]

Minoxidil was introduced in the early 1970s as a treatment for

hypertension. Hypertrichosis was a common side-effect in those taking Minoxidil tablets and

included the regrowth of hair in male balding. There is no marketed formulation of minoxidil

emulgel till date. Therefore, present research has been undertaken with the aim to develop and

evaluate an emulgel formulation of minoxidil.

2. MATERIALS AND METHODS

Minoxidil was procured from Lyra Laboratories Pvt. Ltd, Carbopol-934, Carbopol-940, were

obtained from S D Fine-Chem Limited, Mumbai. Cellophane membrane was procured from the

Spruce Enterprises, Ambala Cantt. The other entire chemicals were used of analytical grade and

without any further chemical modification.

3. PREPARATION OF EMULGEL

The emulgel was formulated in three different steps.

Step 1: Formulation of emulsion either o/w or w/o.

Step 2: Formulation of gel base

Step 3: Incorporation of emulsion into gel base with continuous stirring.

Different formulations were prepared using varying amount of gelling agent. The gel bases were

prepared by dispersing Carbopol 934 and 940 each in distilled water separately with constant

stirring at a moderate speed using mechanical shaker. Formulations F1, F2, F3, and F4 were

prepared by carbopol 934 and F5, F6, F7, and F8 by carbopol 940 as gelling agents. The pH values

of all the formulations were adjusted to 6-6.5 using triethanolamine (TEA). The oil phase of the

emulsion was prepared by dissolving measured amount of Span 20 in light liquid paraffin. The

aqueous phase was prepared by dissolving Tween 20 in distilled water.[4,5]

Methyl and propyl

parabens were dissolved in propylene glycol and mixed with the aqueous phase. Minoxidil and



mentha oil was dissolved in oil phase. Both the oily and aqueous phases were separately heated so

that all the components get properly mixed. The oily phase was added to the aqueous phase slowly

with continuous stirring to form emulsion. The prepared emulsion was mixed with the gel bases i.e.

Carbapol gel bases respectively in 1:1 ratio to form emulgel. The composition of different

formulations has been shown in Table 1.

4. EVALUATION OF MINOXIDIL EMULGEL FORMULATIONS

4.1 PHYSICAL EXAMINATION

All formulations were inspected visually for colour, homogeneity, phase separation, consistency.

The data is shown in Table 2.

4.2 MEASUREMENT OF pH

The pH of emulgel formulations was determined by using digital pH meter. One gram of gel was

dissolved in 100 ml of distilled water and kept for two hours. The measurement of pH of each

formulation was done in triplicate and average values were calculated. The data is reported in

Graph 1

4.3 RHEOLOGICAL STUDY

The viscosity of the formulated batches was determined using a Brookfield Viscometer (RVDV-I

Prime, Brookfield Engineering Laboratories, USA) with spindle no.7 as shown in fig 4.1. The

formulations whose viscosity was to be determined were added to a beaker and kept for 30 min to

maintain them at the assay temperature (25±1ºC) before the measurement. Spindle was lowered

perpendicular in to the centre of emulgel taking care that spindle does not touch bottom of the jar

and rotated at a speed of 50 rpm for 10 minutes.[6]

The spindle was moved up and down giving

viscosities at number of points along the path. The average of three readings was taken and the data

is reported in Graph 2.

4.4 SPRADABILITY

Spreadability was determined by apparatus suggested by Mutimer et al (1956). Spreadability

denotes the extent of area to which gel readily spread on application to skin or affected part. The

therapeutic efficacy of a formulation also depends upon its spreading value. Spreadability is

expressed in terms of time in seconds taken by two slides to slip off from emulgel and placed in

between the slides under the direction of certain load.[7]

Lesser the time taken for separation of two

slides, better the spreadability as shown in Graph3.

It is calculated by using the formula: S = M. L / T

Where M = weight tied to upper slide

L = length of glass slides



T = time taken to separate the slides

4.5 EXTRUDABILITY TEST (TUBE TEST)

Extrudability test is based upon the determination of weight required to extrude 0.5 cm ribbon of

emulgel in 10 sec from lacquered collapsible aluminum tube. More quantity extruded better is

extrudability.[8]

The test was performed in triplicate and the average values were calculated. The

extrudability was then calculated by using the following formula.

Extrudability = Weight applied to extrude emulgel from tube (in gm) / Area (in cm2)

The data is shown in Graph 4.

4.6 DRUG CONTENT DETERMINATION

Accurately weighed 1 gm of emulgel was dissolved in 100 ml of phosphate buffer pH 7.4 in

volumetric flask and kept for 2 hours with occasional stirring. The solution was passed through the

filter paper and filtered. The absorbance was measured spectrophotometrically at 285 nm. The drug

content was determined using standard plot.[9]

and the result is shown in Graph 5.

Drug Content = (Concentration × Dilution Factor × Volume taken) × Conversion Factor

4.7 IN VITRO DRUG RELEASE STUDY

The in vitro drug release studies of the emulgel formulations were carried out in modified Diffusion

cell using Dialysis membrane (Himedia laboratories Pvt Ltd). The membrane was soaked in

phosphate buffer pH 5.5 for 9-12 hours, was clamped carefully to one end of the hollow glass tube

of the cellophane membrane. Then emulgel was spread uniformly on the dialysis membrane. About

50 ml of the phosphate buffer of pH 5.5 was used as dissolution media which was added to the

receptor compartment.[10]

The donor compartment was kept in contact with receptor compartment.

This whole assembly was kept on a magnetic stirrer and the solution on the receptor side was

maintained at 37±0.50C. A similar blank set was run simultaneously as a control. Sample (5ml) was

withdrawn at suitable time intervals and replaced with the equal amounts of fresh dissolution

media. Samples were analyzed spectrophotomtrically at 285 nm and the cumulative percent drug

released was calculated.[11]

as shown in Graph 6.

4.8 STABILITY STUDY

Stability study was performed on F6 formulations. The preparations were packed in collapsible

aluminum tubes (5 g) and subjected to stability study at 25°C and for a period of 2 months. Samples

were withdrawn at interval of 15 days and were evaluated for physical appearance and drug

content. All the result were found to be in limits.[12]

The data is reported in graph 7.



Table 1: Composition of Minoxidil Emulgel Formulation (%w/w)

Ingredients

%(w/w)

Formulation Batches

F1 F2 F3 F4 F5 F6 F7 F8

Minoxidil 1 1 1 1 1 1 1 1

Carbopol

934

0.5 1 1.5 2.0 - - - -

Carbopol

940

- - - - 0.5 1 1.5 2.0

Tween 20 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

span 20 1 1 1 1 1 1 1 1

Liquid

Parafin

7.5 7.5 7.5 7.5 7.5 7.5 7.5 7.5

Propylene

Glycol

5 5 5 5 5 5 5 5

Propyl

Paraben

0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

Methyl

paraben

0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5

Methna oil 1 1 1 1 1 1 1 1

Water q.s q.s q.s q.s q.s q.s q.s q.s

Table 2: Physicochemical characteristics of minoxidil emulgel formulation

S.No Formulation

Code

Colour Phase

separation

Grittiness Homogeneity Consistency

1. F1 White None - Excellent +++


3. F3 White None - Good ++

4. F4 White None - Fair +



7. F7 Transparent None - Excellent +++

8. F8 Transparent None - Good ++

Excellent +++, Good ++, Satisfactory +



Fig 1: FTIR Spectra of Minoxidil

. Fig 2: FTIR Spectra of Minoxidil and Carbapol-934



Fig 3: FTIR Spectra of Minoxidil and Carbapol-940

Graph 1: pH of Different Formulations F1 – F8

5

5.2

5.4

5.6

5.8

6

6.2

6.4

6.6

6.8

F1 F2 F3 F4 F5 F6 F7 F8

pH

Formulation Code



Graph 2: Viscosities of Different Formulations F1- F8

Graph 3: Spreadability of Different Formulations F1-F8

0

5000

10000

15000

20000

25000

30000

35000

F1 F2 F3 F4 F5 F6 F7 F8

Vis

cosi

ty

Formulation code

0

5

10

15

20

25

30

35

F1 F2 F3 F4 F5 F6 F7 F8

Sp

read

ab

ilit

y

Formulation code



Graph 4: Extrudability of different formulations F1 - F8

Graph 5: Drug Content of Formulations

Graph 6: In Vitro Cumulative % Drug Release profile of Formulation F1-F8

0

2

4

6

8

10

12

14

16

18

F1 F2 F3 F4 F5 F6 F7 F8

Extr

ud

ab

ilit

y

Formulation Code

83

84

85

86

87

88

89

90

91

92

F1 F2 F3 F4 F5 F6 F7 F8

% D

rug C

on

ten

t

Formulation code

0

10

20

30

40

50

60

70

80

0 200 400 600 800

% C

um

ula

tive

Dru

g

Rel

ease

d

Time (hours)

F1

F2

F3

F4

F5

F6

F7

F8



Graph 7: Stability Study of Emulgel Formulation F6

5. DISCUSSION

Minoxidil is a potent vasodilator and promote hair growth, used for the topical as well as for

systemic delivery. In the present study, an attempt was made to formulate topical emulgel of

minoxidil for efficient delivery of drug across the skin. Emulgel formulations were prepared and

evaluated on the basis of characteristic physicochemical parameters, in vitro drug release and

stability.

The purity of the drug carried out by FTIR spectrum of the drug sample, which is in agreement

with standard IR spectrum of minoxidil. The FTIR spectrum of drug sample has been shown in

Fig. 1. The physical and chemical interaction between drug and the excipients were studied using

FTIR technique. It has been observed that there is no chemical interaction between the Minoxidil

and the polymers used. Hence, there was no interaction between the drug and the polymers. So

they can be successfully incorporated in the Emulgel. The FTIR spectrums of the drug and

polymers are shown in Fig. 2, 3.

The pH of the formulations was in the range of 5.5 - 6.6 which was similar to pH of the skin.

Results are shown in Graph 1.

The viscosity of the formulation batches were checked by using Brookfield viscometer. The

results are shown in Graph 2. According to the results, the viscosity differs in accordance to the

concentration of the gelling agent used in different formulations. From the data it has been

revealed that the formulations with Carbopol-940 are more viscous than Carbopol-934.

Spreading coefficient was determined using modified spreading coefficient apparatus. The

results are shown in Graph 3. From the results it can be concluded that formulations containing

Carbopol-940 as gelling agent showed better spreading coefficient than those containing

Carbopol-934 as gelling agent.

87

88

89

90

91

92

93

0 days 15days 30 days 45 days 60 days

% D

rug C

on

ten

t

Days



Extrudability test was carried out using collapsible aluminium tube. The results are shown in

Graph 4. The formulation F6 with 1% carbopol 940 showed desired extrudability as compared to

carbopol 934.

The drug content was determined for all the formulation by UV spectrophotometer method. The

results of the drug content varied between 84% to 92.4% as shown in Graph 5. The results

indicated that the drug dispersed uniformily throughout the emulgels which could be due to high

entrapment of drug in the internal phase of emulsion. Formulation F6 with 1% Carbopol 940

showed maximum 92.4% of drug content and was selected as best formulation.

The results of in-vitro drug release from the different formulation are shown in Graph 6. The

Cumulative amount of drug release from formulations F1, F2, F5, F6 showed better release in

12hrs i.e 75.03%, 71.00%, 70.25% and 64.22% respectively. This study clearly indicated that as

the concentration of polymer increases the amount of drug released decreases. The result proved

that formulation F6 were found to be best formulation among all.

Stability studies of F6 formulations were performed at 25◦C for a period of two months.

Formulations were evaluated for drug content and physical appearance. The test results of the

study are presented in Graph 7. The stability of the emulgel was found to negligibly changed

after storage at specified conditions.

6. CONCLUSION

From the above results it was concluded that the Minoxidl Emulgel formulations prepared with

Carbopol-934 and Carbopol-940 showed acceptable physical properties and drug release.

However, the carbopol-940 based emulgel with 1% concentration (F6) proved to be formula of

choice, since it showed acceptable drug release and highest drug content. The stability of

formulation (F6) at 250C was found to negligibly change after storage at specified conditions.

Thus, designing of minoxidil emulgel topical drug delivery would improve the efficacy of drug.

7. ACKNOWLEDGEMENT

The authors are thankful to Lyra Laboratries Pvt.Ltd ( Baddi, India) for providing a gift sample of

Minoxidil. The authors are also grateful to the Director, Rayat College of Pharmacy, Railmajra,

Punjab Dr. Naresh Singh Gill for providing the necessary facilities to carry out this work.



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9. Sera UV, Ramana MV, (2006), In vitro skin absorption and drug release – a comparison

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224| p a g e international standard serial number …. rpa15162363015.pdfemulgel have emerged as one...

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