Indira Institute Of Professional Studies Sheikhpura Purachindwada Bhopal 462036.
Multiple emulsions have been proposed for the enhancement of drug bioavailability or as a onset off action for prolonged drug delivery system. Multiple emulsions are often stabilized using a combination of hydrophilic and hydrophobic surfactants. In the present study using W/O/W formulation for prepare of multiple emulsion of ranitidine hydrochloride where analysed the physical parameters and evaluation, during this study most of globular size is ± 5 ?g viscosity is shows the non-Newtonian flow, and the percentage entrapment efficacy is good for drug penetration.
Multiple Emulsion: -
Multiple emulsions are defined as emulsions in which both types of emulsions, i.e. water-in-oil (w/o) and oil-in-water (o/w) exist simultaneously. (K,Rajesh) Multiple emulsion of heterogeneous system where one immiscible liquid is dispersed is another in the form of droplets and stabilized. Low Thermodynamic stability. Continuous phase or dispersed phase. Multiple emulsion are complex system and may be called “emulsion of emulsion”, “double or triple emulsions” since the internal phase itself contains dispersed globules which are miscible with the continuous phase based up on the dispersed medium. (S,Pooja I.P 2007)
Ranitidine Hydrochloride: - ranitidine hydrochloride are using for the H2 anti-histaminic. Ranitidine hydrochloride is no anti-androgenic action, less permeability in to the brain does not significantly inhibit hepatic metabolism, over all incidence of side effects is lower. (Triparhi,K.D. Vyas S,P)
Choice of drug: - ranitidine hydrochloride is less toxic as and more effective as compare to other types of anti-histaminic drugs. Ranitidine shows the onset of action for prolonged release.
Types Of Multiple Emulsion: -
O/W/O Emulsion System: -
The O/W/O systems an aqueous (hydrophilic) phase separates internal and external oil phase. In other words, the water-in-oil-water (O/W/O) is a system in which water droplets may be surrounded in oil phase, which is true encloses one or more oil droplets of multiple emulsion. (G, Sumana)
W/O/W Emulsion System: -
The W/O/W systems, an organic (hydrophobic) phase separates internal and external aqueous phases. In other words, water-oil-water (W/O/W) is a system in which oil droplets may be surrounded by an aqueous phase, which is term encloses one or several water droplets. (G, Sumana)
Preparation Of multiple Emulsion by two step method
MATERIAL & METHODS
The following chemicals were obtained commercially and were used without further purification. All chemicals used were of the purest grade available the gifted sample of Ranitidine hydrochloride was obtained by PARKBENZ Labourites PVT. Ltd. Mandideep Bhopal, For the preparation of multiple emulsion using span80, tween 80, cmc (carboxy methyl cellulose)
Oil phase :- for the oil phase using (liquid paraffin) as per different concentration for different formulation. Emulsifying agents:- using span 80, span 20. Viscosity imperting agent:- tween 80, cmc
Formulation and Evaluation:-
Three formulation of different W/O/W emulsion were prepared using different ratio of emulsifier and viscosity imparting agent primary and secondary emulsion were prepared as per table no. 01(G,Sumana)
Trial Formulation Of Different Concentration
For Primary Preparation 2000 RPM of Different Formulation for 30 min.
|
Ingredients |
F1 |
F2 |
F3 |
|
Drug |
20 |
25 |
30 |
|
Liquid paraffin |
15 |
18 |
21 |
|
Span 80 |
1.5 |
2 |
2.5 |
|
Water |
12 |
15 |
18 |
For Secondary Preparation 2000 Rpm Of Different Formulation for 15 min.
|
Primary Emulsion |
12 |
15 |
18 |
|
Tween 80 |
0.5 |
1.0 |
1.5 |
|
Water |
30 |
30 |
30 |
|
Cmc |
2 |
3 |
4 |
|
P value (%) |
82 |
87 |
90 |
Evaluation:-
(A) Organoleptic evaluation :-
1. General appearance - white or pale yellow crystalline powder
2. Solubility
Freely soluble in water.
Sparingly soluble in anhydrous ethanol
Very slightly soluble in methylene chloride(B.P 2007, USP 2004)
(B)Measurement of globular size:-
Globular size of multiple emulsion was determined by microscopic method size of globular were determined by using tri-ocular microscope firstly the microscope is calibrated using the ocular and stage micrometer.(m, alfred)
Globular size= stage sizeoculer size
×100
Fig. 1.1 microscopic image of multiple emulsion of w/o/w
For formulation f1
Multiple emulsion was spread the slide by using aqueous and non aqueous dye for the determination of globular
size. Size of 100 globules were measured from different microscopic field.
Table 02. size distribution of globules in formulation f1
|
S. n. |
Range |
No. of globules |
|
1. |
10-20?m |
25±4 |
|
2. |
20-40?m |
40±2 |
|
3. |
20-30?m |
20±2 |
|
4. |
25-40?m |
15±3 |
For formulation f2
Multiple emulsion was spread the slide by using aqueous and non-aqueous dye for the determination of globula
size. Size of 100 globules were measured from different microscopic field.
Table 03. size distribution of globules in formulation f2
|
S. n. |
Range |
No. of globules |
|
1. |
10-20?m |
40±5 |
|
2. |
20-40?m |
25±3 |
|
3. |
20-30?m |
20±2 |
|
4. |
25-40?m |
15±2 |
For formulation f3
Multiple emulsion was spread the slide by using aqueous and non aqueous dye for the determination of globular
size. Size of 100 globules were measured from different microscopic field.
Table 03. size distribution of globules in formulation f3
|
S. n. |
Range |
No. of globules |
|
1. |
10-20?m |
25±4 |
|
2. |
20-40?m |
40±3 |
|
3. |
20-30?m |
20±2 |
|
4. |
25-40?m |
15±2 |
(B) Viscosity:-
The viscosity of the all formulation were determined using brokfield viscometer by using spindal 64. Determination of viscosity of prepared formulation by using different RPM using 64 no. of spindal to determine flow property of multiple emulsion. (vyas s,p & lachman leon)
Compare the viscosity of multiple emulsion (w/o/w) is show in graph
Graph 1. Represent the visosity of different prepared formulation (f1,f2,f3)
(C) Entrapment Efficiency
The Percentage Entrapment Efficiency (?) was determined for the drug content in preparation for the measurement of Percentage Entrapment Efficiency taking freshly prepared W/O/W multiple emulsions different sample (A,B,C) and immediately centrifuged at 4000 rpm for 10 min. Then 1ml of the aqueous phase (the lower layer) was precisely withdrawn through 2 ml hypodermic syringe and diluted properly with phosphate buffer 6.8. The solution was filtered with a Millipore filter (0.22 mm in pore size) and drug content was analyzed on UV spectrophotometer at 247.6 nm. The Encapsulation Efficiency was determined by following equation (lachman, leon)
% Drug Entrapment Efficacy=TOTAL DRUG IN CORPORATED-FREE DRUG TOTAL DRUG×100
Graph 2. Represent % Entrapment of Drug.
Instruments Used
|
S. N |
Name |
Manufacturer |
|
01 |
Electronic Weighing Balance |
Citizen India |
|
02 |
UV Spectrometer |
Shimadzu-1700 Japan |
|
03 |
Melting Point Apparatus |
Jindal, India |
|
04 |
Ph Meter |
M.S. Electronics, India |
|
05 |
Micro Centrifuge |
Remi-21c, Japan |
|
06 |
Vortex Mixture |
Spinix, Japan |
|
07 |
Ultra Sonicator |
Pci, Japan |
|
08 |
Brookfield Viscometer |
Japan |
P' value
Graph 3.0 Represent the p’value
effect of various viscosity imparting agent on the stability of multiple emulsions.
|
Formulation |
Viscosity Imparting Agents |
Conc. In % W/V |
Feature |
P-Value |
|
S1 |
PVP |
0.5 |
Unstable |
Nil |
|
S2 |
1.0 |
Less viscous |
64.8 |
|
|
S3 |
CMC |
0.5 |
Moderately viscous |
30.2 |
|
S4 |
1.0 |
More viscous |
15.6 |
|
|
S5 |
PEG-20 |
0.5 |
Less viscous |
59.0 |
|
S6 |
1.0 |
Moderately viscous |
35.2 |
|
|
S7 |
HPMC |
0.5 |
Moderately viscous |
34 |
|
S8 |
1.0 |
less viscous |
28 |
RESULT AND DISCUSSION: -
Multiple emulsions are often stabilized using a combination of hydrophilic and hydrophobic surfactants. The ratio of these surfactants is important in achieving stable multiple emulsions. The viscosity of an emulsion can be of crucial importance for the stability of multiple emulsions, specially the viscosity of the external phase.
Melting Point Determination: - Melting point of ranitidine HCL was found at 68-71 ºC.
Determination Of Globular Size Of Prepared Multiple Emulsion: - The globular size of prepared formulation is 5-50?g.
Determination Of Viscosity Of Prepared Multiple Emulsion: -
The viscosity of prepared multiple emulsion of ranitidine hydrochloride is good it will shows non-Newtonian flow.
Determination Of % Entrapment Efficacy: -
The % Entrapment efficacy of prepared formulation is good it’s entrapment efficacy is more then 92%.
REFERENCES
Mohd Sajjad*, Formulation And Evaluation Of Multiple Emulsion Ranitidine Hydrochloride, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 11, 542-547. https://doi.org/10.5281/zenodo.14067766
10.5281/zenodo.14067766
