Formulation and Charecterisation of Multiple Emulsions With Various Additives

International Journal of Research in Pharmaceutical and Biomedical Sciences
ISSN: 2229-3701
______________________________________________________________________Research Paper
Formulation and Charecterisation of Multiple Emulsions With Various Additives

Sumana Ghosh Gurunanak Institute of Pharmaceuttical Sciences And Technology ___________________________________________________________________________________________
Abstract 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,specialy the viscosity of the external phase. The electrolytes,proteins,sugars and drugs affect the viscosity of the multiple emulsion. The objective of this study was to evaluate the long-term stability of water-in-oil-in-water (W/O/W) multiple emulsions with respect to the concentrations of Span 80, and Tween 80. In addition, the effect of surfactant,viscosity-imperting agents, on emulsion bulk rheological properties was investigated. Light microscopy, creaming volume, and rheological properties were used to assess emulsion stability. It was observed that the optimal surfactant concentrations for W/O/W emulsion long-term stability were 10%vol/vol Span 80 in the oil phase and 0.3%vol/vol Tween 80 in the continuous phase. Higher concentrations of Tween 80 had a destructive effect on W/O/W emulsion stability, which correlated with the observation that interfacial film strength at the oil/water interface decreased as the Tween 80 concentration increased. High Span 80 concentrations increased the storage modulus G (solidlike) values and hence enhanced multiple emulsion stability. However, when 10% vol/vol Span 80 was incorporated, the viscosity of the primary W/O emulsion increased considerably and the emulsion droplets lost their shape. The stirring speeds of the motor in primary and secondary emulsion affect the viscosity and stability of the multiple emulsions. The stirring speed in case of primary emulsion is 2000 RPM for 30 min. and in case of emulsion it is 400 RPM for 10 min. to gate a stable multiple w/o/w emulsion.Various additives also affect the stability of the multiple emulsions. Affect of various viscosity imparting agents are used with the water phase of the secondary emulsions in order to increase the stability as well as the stability of the emulsions. Key words: multiple emulsions, span 80, tween 80.
INTRODUCTION An ideal dosage regimen in the drug therapy of any disease is the one which immediately attains the desired therapeutic concentration of drug in plasma(or in the site of action) and maintains it constant for the entire duration of treatment. For many decades treatment of an acute disease or a cronic illness has been mostly accomplished by delivery of drugs to patients using various pharmaceutical dosages forms, including tablets,capsules,pills,suppositories,creams,ointment s,liquids,aerosols,and injectables,as drug carriers. Even today these conventional drug delivery systems are the pharmaceutical products commonly seen in the prescription and over-the-counter drug marketplace. This type of drug delivery system is known to provide a prompt release of drug.Therefore,to achieve as well as to maintain the drug concentration within the therapeutical effective range needed for treatment, it is often necessary to take this type of drug delivery system several times a day. This results in a significant fluctuation in drug levels.
Recently, several technical advancements which have resulted in the development of new techniques for drug delivery. These techniques are capable of controlling the rate of drug delivery, sustaining the duration of therapeutic activity, and/or targeting the delivery of drug to a tissue. Although these advancements have led to the development of several noval drug delivery systems that could revolutionaries the method of medication and provide a number of therapeutic benefits. The sustained release dosage form has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent such that its appearance in the systemic circulation is delayed and or prolong and its plasma profile is sustained in duration. The onset of pharmacologic action is often delayed, and the duration of its therapeutic effect is sustained. In the controlled release drug delivery system the release of drug ingredients from a controlledrelease drug delivery system proceeds at a rate
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ISSN: 2229-3701
profile that is not only predictable kinetically but also reproducible from one unit to another. Administered into the body. This gives high therapeutic efficacy with minimal toxicity. It gives better selectivity of pharmacological activity, and reduce patient compliance by reducing the dosing interval. Numerous attempts have been made to device clinically effective drug delivery systems. The controlled drug delivery system makes an agent to do its best when Various drug carrier systems have been developed including nanoparticles, liposomes, serum albumin microbeads, erythrocytes, microcapsules, microemultions, niosomes, multiple emulsions etc. The controlled drug delivery systems may be classified as Polymer controlled and Non-polymer controlled The polimer controlled systems include transdermal patches,microcapsules,ocusarts etc.whereas non polymer systems are comprised of iposomal drug delivery systems,in which the drug is encapsulated in phospholipids vesicles. Erythrocytes,which are impregnated with the drug using hypotonic saline solution and then to be administered perentrally. Liquid membrane systems like multiple emultions.
aqueous phases can behave like a membrane controlling solute release. Liquid membrane emulsions of the o/w/o type have been used to separate hydrocarbons where the aqueous phase serves as the membrane and a solvent as the external phase. The system w/o/w on the other hand can extract contaminents from waste water, which acts as the external phase. PREPARATION OF MULTIPLE EMULSIONS There are two main method,for the preparation of multiple emulsions. Two step method Phase inversion technique
EXPERIMENTAL PART MATERIALS AND METHODS CHEMICALS: The following chemicals were obtained commercially and were used without further purification. All chemicals used were of the purest grade available. A. FORMULATION USING DIFF.CONC.OF SPAN 80. Non-medicated emulsions were prepared by taking liquid paraffin as oil phase and water as aqueous phase using span 80 as emulsifier .For the preparation of multiple emulsions Tween 80 is used. The formulation is stabilized by taking different conc. of primary and secondary emulsifying agents. EVALUATION Prepared emulsion were taken in a measuring cylinder and placed in undisturbed position for 24 hr. and evaluated whether they craked or creamed and if they are cracked then the P-VALUE was determined. RESULT From the observation of P value it is found that the p value of the formulation F2 is low with respect to the other. So this formulation F2 is more stable. So the formulation F2, contain 10% v/v span 80 is selected for further study. EVALUATION
MULTIPLE EMULTIONS: Multiple emulsions are complex liquid description systems in which the droplets of the one dispersed liquid are further dispersed in another liquid. The inner dispersed globule/droplet in the multiple emulsions are separated from the outer liquid phase by a layer of another phase. There are mainly two types of multiple emulsions W/O/W AND O/W/O emulsions.Although,w/o/w emulsions have many of the attributes of w/o emulsions, their lower viscosity, derived from water as the external phase, makes them easier to inject.Adjuvent effects have been reported to be improved compared to w/o emulsions or aqueous solution of antigen. similar increase in the activity of the anticancer drug delivery using multiple emulsion have been observed. The most promising use of multiple emulsions is in the area of sustained release, drug formulation since the oil layer between the two
Vol. 2 (2) Apr Jun 2011
752
ISSN: 2229-3701
Prepared emulsion were taken in a measuring cylinder and placed in undisturbed position for 24 hr. and evaluated whether they craked or creamed and if they are cracked then the P-VALUE was determined. RESULT From the observation of P value it is found that the p value of the formulation F2 is low with respect to the other. So this formulation F2 is more stable. So the formulation F2b, contain 10% v/v span 80 and 0.3 % v/v tween 80 is selected for further study. Primary stirring speed was selected at 2000 rpm for 30 min. and secondary stirring speed was selected at600 rpm for 10 min. EVALUATION Prepared emulsion were taken in a measuring cylinder and placed in undisturbed position for 24 hr. and evaluated whether they craked or creamed and if they are cracked then the P-VALUE was determined. RESULT
and if they are cracked then the P-VALUE was determined. RESULT From the above table it is found that the formulation A5, A6, A10 and A14 shows moderate viscosity. But the formulation A14 is more stable as study from the p value. Also this formulation has very nice viscosity with good pourability. So the formulation F14 containing 0.5% w/v CMC is selected for further study.
CONCLUSION: So the w/o/w multiple emulsion containing 10% span80 and0.3% tween80 and 0.5% CMC is more stable at roomtemperature.
Ext.acq phase Internal acq. Phase Middle oil phase
From the observation of P value it is found that the p value of the formulation D2 is low with respect to the other. So this formulation D2 is more stable. So the formulation D2, in which the oil, water ratio is 7:3 in primary emulsion and the primary emulsion, water ratio is 3:7 in secondary emulsion, is selected for further study. SELECTION OF STIRRING SPEED: The initial decrease in size may be due to complete dispersion of aggregates of the oil droplets. After the decrease to the minimum size the droplet size increased due to coalescence of the droplets. Here greatest decrease in droplet size was occurring in 400 rpm. So it is conclude that the coalescence of droplet is minimum in 400 rpm. So selected second stirring speed of the formulation is 400 rpm. EVALUATION Prepared emulsion were taken in a measuring cylinder and placed in undisturbed position for 24 hr. and evaluated whether they cracked or creamed
W/O/W multiple emulsion
Int .acq phase external acq. Phase Middle oil phase
O/W/O multiple emulsion
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ISSN: 2229-3701
CHEMICALS:
The following chemicals were obtained commercially and were used without further purification. All chemicals used were of the purest grade available. Light liquid paraffin, PVP, Methyl cellulose, carboxy methyl cellulose from G.S.Chemical Testing lab.&allied industries. Tween 80, span 80, polymethyl methacrylate from Himedia laboratories Pvt ltd, Mumbai. INSTRUMENTS USED Single pan electronic balance (anamed laboratory), analytical balance (dhona lab, calcutta), remi stirrer with speedometer (remi equipments, bombay), microscope (adco), digital pH meter (systronics), UV double beam spectrophotometer model 2 (genesys thermospectronic), research centrifuge TC4100D (Eltek), 2MH magnetic stirrer (remi equipments Pvt Ltd)
FORMULATION DEVELOPMENT FOR A STABLE W/O/W EMULSION4
Micro fine drug Adding drop wise into the oil phase at high RPM
INTERNAL AQUEOUS PHASE(WATER)
OIL (LIGHLIQUID PARAFFINE) + EMULSIFYING AGENTS SPAN80
WATER + EMULSIFYING AGENT TWEEN80+VISCOSIY T IMPERTING AGENTS
Adding drop wise to water phase at low RPM
FORMATION OF W/O PRIMERY EMULSION.
FORMATION OF W/O/W MULTIPLE EMULSIONS
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TRIAL 1: FORMULATION OF MULTIPLE EMULSION WITH DIFF.CONC. OF SPAN 80: Primary emulsion: RPM 1000 for 30 min.
Ingredients Liquid paraffin(ml) Span 80(%v/v) Water(ml) F1 30 5 20 F2 30 10 20 F3 30 12 20 F4 30 15 20
Secondary emulsion: RPM 200 for 10 min.

Primary emulsion(ml) Tween 80(%v/v) Water P value (%) 15 0.5 35 82 15 0.5 35 64 15 0.5 35 95 15 0.5 35 98
P-VALUE :
OBSERVATION OF P-VALUE
100 90 80 70 60 'P' VALUE 50 40 30 20 10 0 F1 F2 F3 F4 FORMULATION
TRIAL 2: FORMULATION OF MULTIPLE EMULSIONS WITH DIFF.CONC. OF TWEEN 80:
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Primary emulsion: 1000 RPM for 30 min.

Ingredients Liquid paraffine(ml) Span 80(%v/v) Water(ml) F2a 30 10 20 F2b 30 10 20 F2c 30 10 20 F2d 30 10 20
Secondary emulsion: 200 RPM for 10 min.

Primery emulsion(ml) Tween 80(%v/v) Water P value(%) 15 0.1 35 51 15 0.3 35 46 15 0.6 35 76 15 1.0 35 86
OBSERVATION OF P-VALUE
90 80 70 60 50 P-VALUE 40 30 20 10 0 F2a F2b F2c F2d FORMULATION
TRIAL 3: FORMULATION BY CHANGING THE RPM BOTH FOR PRIMERY AND SECONDARY EMULSION:
Primary emulsion: RPM 2000 for 30 min.

Ingredients Liquid paraffin(ml) Span 80(%v/v) Water(ml) F2b-1 30 10 20 F2b-2 30 10 20 F2b-3 30 10 20 F2b-4 30 10 20
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Secondary emulsion: RPM 600 for 10 min.

Primery emulsion(ml) Tween 80(%v/v) Water P value(%) 15 0.1 35 30 15 0.3 35 24 15 0.6 35 64 15 1.0 35 83
OBSERVATION OF P VALUE
90 80 70 60 50 P-VALUE 40 30 20 10 0 1 2 3 FORMULATION 4 5
TRIAL 4: FORMULATION BY ALTERING THE VOL. OF OIL AND WATER BOTH IN PRIMERY AND SECONDARY EMULSION PRIMERY EMULSIONS: 2000 RPM for 30 min.
Ingredients Liquid paraffin(ml) Span 80(%v/v) Water(ml) D1 35 10 15 D2 35 10 15 D3 30 10 20 D4 40 10 10
SECONFARY EMULSIONS: 600 RPM for 10 min.

Primary emulsion(ml) Tween 80(%v/v) Water P value(%) 20 0.3 30 28 15 0.3 35 21 10 0.3 40 45 5 0.3 45 cracking
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OBSERVATION OF P -VALUE
P- V A LU E
45 40 35 30 25 20 1 5 1 0 5 0 D1 D2 D3 D4 F O R M U LA T I O N
TABLE 5: EFFECT OF SECOND STIRRING SPEED:
Sl. no. 1 2 3 4
STIRRING SPEED
INITIAL DIA.
MINIMUM DIA.
DECREASE
DAYS REQUERED TO REACH MIN.SIZE.
400 600 800 1000
17.30 +_ 1.85 16.88+_ 1.425 15.63+_ .889 12.50+_.825
15.75 +_ 1.2 15.63+_ .889 14.50+_ .725 11.63+_.300
8.96 7.40 7.20 6.96
1 3 4 5
TABLE 6: EFFECT OF VARIOUS VISCOSITY IMPARTING AGENT ON THE STABILITY OF MULTIPLE EMULSIONS.
FORMULATION A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 A11 A12 A13 A14 A15 A16 VISCOSITY IMPERTING AGENTS CONC. IN % W/V 0.25 0.5 1.0 1.5 0.25 0.5 1.0 1.5 0.25 0.5 1.0 1.5 0.25 0.5 1.0 1.5 FEATURE Unstable Unstable Less Viscous Less Viscous Less Viscous Moderately viscous Moderately viscous More viscous Less Viscous Moderately viscous More viscous More viscous Less Viscous Moderately viscous More viscous More viscous P-VALUE % NIL NIL 70.8 36.5 66.0 26.0 38.0 17.8 48.2 32 12.5 19.7 35.55 21.60 10.60 17.20
PVP POLY METHYL METHACRILATE
MC
CMC
Result: Most stable emulsions is the emulsions produced with CMC at 0.5 % conc.
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OBSERVATION OF P VALUE 80 70 60 50 P-VALUE 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 FORMULATION

REFERENCES 1. Matsumoto S, Kita Y, Yonezawa D. An attempt at preparing water- in-oil-in-water multiple phase emulsions. J Colloid Interface Sci. 1976;57:353-361. 2. Opawale FO, Burgess DJ. Influence of interfacial rheological properties of mixed emulsifier films on the stability of water-in-oilin- water emulsions. J Pharm Pharmacol. 1998;50:965-973. 3. Sherman P. Rheological Properties of Emulsions. In: Becher P. ed. Encyclopedia of Emulsion Technology, Volume 1: Basic Theory. New York, NY: Marcel Dekker; 1983:215248. 4. Pal R, Rhodes E. Emulsion flow in pipelines. Int J Multiphase Flow. 1989;15:1011-1017.
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Formulation and Charecterisation of Multiple Emulsions With Various Additives

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International Journal of Research in Pharmaceutical and Biomedical Sciences