Formulation and Evaluation of Ornidazole Topical Emulgel
Formulation and Evaluation of Ornidazole Topical Emulgel
Formulation and Evaluation of Ornidazole Topical Emulgel
1
Assistant Professor, Sree Chaitanya Institute of Pharmaceutical Sciences, LMD Colony,
Thimmapur, Karimnagar, Telangana.
2
Sree Chaitanya Institute of Pharmaceutical Sciences, LMD Colony, Thimmapur,
Karimnagar, Telangana.
INTRODUCTION
Topical delivery can be defined as the application of a drug containing formulation to the
skin to directly treat cutaneous disorders [e.g. acne, psoriasis] with the intent of containing
the pharmacological or other effects of drug to the surface of the skin or within. Topical drug
administration through various routes applied a wide spectrum of preparation for both
cosmetic and dermatological, to their health and diseased skin. Topical preparations are
applied to the surface of a part of the body and have effects only in a specific area of the body
and are formulated in such a manner that the systemic absorption of the medicament is
minimal. The most common examples of topical dosage forms are solutions, suspensions,
emulsions, semisolids [e.g. powders and aerosols] among them ointments, creams, and
lotions have numerous disadvantages.
They are usually very sticky and cause uneasiness to the patient when applied moreover they
also have less spreading coefficient and need to apply with rubbing. They also exhibit the
problem of stability. Due to all these factors, a major group of semisolid preparation,
transparent gel has expanded its use in both cosmetics and in pharmaceutical preparation.
Inspite of many advantages of gels a major limitation is their inability an emulsion based
limitation an emulsion based approach is being used so that a hydrophobic therapeutic moiety
can be successfully incorporated and delivered through gels. When gels and emulsions are
used in combined form the dosage forms are referred as emulgels.
interact at the polar head groups of the lipids, within aqueous region between lipid head
group and between the hydrophobic tails of the barrier. The common mechanism is to protect
the body for unwanted particles from the environment. The main barrier of the skin is located
in the outermost layer of skin that is epidermis. Since the lipid regions in the stratum corneum
forms the only continuous structure, substance applied on to the skin always have to pass
these region. The major obstacle for topical drug delivery is the low diffusion rate of drug
across the stratum corneum. Several methods have been assessed to increase the permeation
rate of drugs temporarily.
Emulgel
Emulgels are emulsions, either of the oil-in-water or water in oil type which are gelled by
mixing with gelling agent. Emulsified gel is stable one and superior vehicle for hydrophobic
or poorly water soluble drugs. In short emulgels are the combination of emulsion and gel.
Advantages of emulgel
1. Increased patient acceptability.
2. Provide targeted drug delivery.
3. Easy termination of the therapy.
4. Improve bioavailability and even the low doses can be effective in comparison with other
conventional semi solid preparation.
5. Stable formulation by decreasing surface interfacial tension resulting in increase in
viscosity of aqueous phase, more stable than Transdermal preparations that are comparatively
less stable, powders are hygroscopic, creams shows phase inversion or breaking and ointment
shows rancidity due to oily b
Disadvantages
1. Poor absorption of macromolecules.
2. Entrapment of bubble during formulation.
3. Hydrophobic drugs are the best choice for such delivery systems.
4. skin irritation or allergy reaction on contact dermatitis.
5. Can be used only for drugs which require very small plasma concentration for action.
6. Enzyme in epidermis may denature the drugs
1) Macroemulsions gel
These are most common type of emulgels where the particle size of droplets of emulsion is
more than 400nm. They are visually opaque but the individual droplets can be easily
observed under microscope. Macroemulsion are thermodynamically unstable, but can be
stabilized using surface active agents. E.g. Khullar R. et al, mefenamic acid emulgel was
prepared using Carbopol 940 as gelling agent. Liquid paraffin was used as oil phase. Mentha
oil and clove oil was used as penetration enhancer. Then it was evaluated for rheological
studies, spreading coefficient studies, skin irritation test, in-vitro release, etc.
2) Nanoemulsion gel
When nanoemulsion is incorporated into gel it is called as nanoemulgel. Nanoemulsion are
thermodynamically stable transparent (translucent) dispersions of oil and water stabilized by
an interfacial film of surfactant and co surfactant molecules having a droplet size of less than
100nm. Nanoemulsion formulations possess improved Transdermal and dermal delivery
properties in vitro as well as in vivo. This has improved transdermal permeation of many
drugs over the conventional topical formulations such as emulsions and gels.
E.g. Singh B. P et al, prepared Carvedilol nanoemulgel using oleic acid and isopropyl
myristate (3:1) as oil phase. Tween 20 and Carvedilol were used as surfactant and co
surfactant respectively. Carbopol 934 was used as gelling agent.
Formulation considerations
The challenges in formulating the topical emulgels are
Determining systems that are non-toxic, non-irritating, non-comedogenic and non-
sensitizing.
The emulgel formulation must have good physiologically compatable and high
biocompatibility.
Formulation cosmetically elegant emulgel.
a) Aqueous material
This forms the aqueous phase of the emulsion. Commonly used agents e.g. water, alcohols.
b) Oils
These agents from the oily phase. For externally applied emulsions, mineral oils, either alone
or combined with soft or hard paraffin’s are widely used. In oral preparations non-
biodegradable mineral and castor oils that provide a local laxative effect and fish liver oils or
various fixed oils of vegetable origin (e.g.: arachis, cottonseed, and maize oils) as nutritional
supplements.
2) Emulsifier
Emulsifying agents are used both to promote emulsification at the time of manufacture and to
control stability during a shelf life. e.g.: Polyethylene glycol 40 stearate, Sorbitan mono-
oleate (Span 80), Polyoxyethylene Sorbitan monooleate (Tween 80), Stearic acid, Sodium
stearate.
3) Gelling agent
These are used to increase consistency of dosage form and provide gelled behavior. Gelling
agent are of 2 types natural and synthetic. Incorporation of gelling agent to a system makes it
thixotropic. It is observed that there exist an inverse relationship between concentration of
gelling agent and extent of drug released. Then get hydrated and swell. Besides its
hydrophilic nature, its cross-linked structure and its insolubility in water makes carbopol a
potential candidate for use in controlled release drug delivery system. HPMC emulgel shows
better drug release than carbopol. Ex: carbopol-934(1%), HPMC-2910(2.5%).
7) Gelling agents: These are the agents used to increase the consistency of any dosage form
can also be used as thickening agent. E.g. Carbapol 934, carbapol 940, HPMC, HPMC-2910,
sodium CMC.
8) Permeation enhancer: These are agents that partition into and interact with skin
constituents to induce a temporary and reversible increase in skin permeability. E.g: Oleic
acid, lecithin, isopropyl myristate, urea, eucalyptus oil, chenopodium oil, pyrrolidone,
laurocapran, dimethyl sulphoxide, linoelic acid, menthol.
mixed into gel base. This may be proving better stability and release of drug than simply
incorporating drugs into gel base.
Method of preparation
It consist of 3 steps
Step-1: formulation of emulsion either o/w or w/o
preparation of oil phase: oil phase of the emulsion is prepared by dissolving emulsifier.
E.g: span 20 in oil phase lie light liquid paraffin.
Step-2 formulation of gel base: prepared by dispersing polymer in purified water with
constant stirring at a moderate speed using mechanical shaker, then the pH was adjusted to 6-
6.5 using tri ethanolamine (TEA).
Step-3 incorporation of emulsion into gel base: Add glutaraldehyde in during mixing of gel
and emulsion in ratio of 1:1 to obtain emulgel.
The main aim of the present study was to formulate the ornidazole emulgel so as to rerain the
formulation for prolong period of time and delivery of the drug to desired site of absorption.
To overcome the limitations of hydro gels in the delivery of hydrophobic drugs. To evaluate
and formulate the ornidazole topical emulgel. To develop an emulsion based gel formulation
for a antimicrobial, antifungal infections of ornidazole To overcome the limitations of hydro
gels in the delivery of hydrophobic drugs.
METHODOLOGY
Standard Graph of Ornidazole
Accurately weighed 100mg of ornidazole powder was dissolved in 10 ml of distilled water
and the volume is made upto 100ml. this is known as primary stock solution and contains
1mg/ml of drug. From the primary stock 10 ml of solution was diluted to 100ml with water.
This is known as secondary stock solution and contains 100g/ ml of drug. Then
spectrometer was scanned using water as a blank between 200- 400 nm to get max of
ornidazole was detected by UV-Spectrophotometer at 318nm. Based on the absorbance of
dilutions the graph was plotted by taking absorbancy on Y- axis and concentration on X- axis.
Formulation
1. Preparation of Emulsion
A) Preparation of Aqueous Phase
The aqueous phse of the emulsion was prepared by dissolving tween 80 in purified water.
B) Preparation of oil Phase: Methyl parabeen and propyl paraben were dissolved in
propylene glycol where as drug was dissolved in ethanol and both solution were mixed with
aqueous phase. Both the oily and aqueous phase were separately heated to 75◦c. then the oil
phase was added to the aqueous phase with continous stirring until cooled to room
temperature.
2. Preparation of gel: The gel bases were prepared by dispersing different concentrations of
polymers in distilled water separately with constant stirring at a moderate speed using
mechanical shaker. The pH of all formulations was adjusted to 6 - 6.5 using triethanolamine
(TEA).
3. Preparation of Emulgel: The obtained emulsion was mixed with the gel with gentle
stirring to obtain the emulgel.
PH Evaluation: pH evaluation is the important criteria especially for the topical formulation.
The pH of emulgel should be between 5.8 – 6 to mimic the skin condition. If the pH of the
prepared emulgel is acidic or basic, it may cause irritation to the patient. PH of the prepared
emulgel was measured using digital pH meter by dipping the glass electrode into an emulgel.
The measurement of pH of each formulation was done in triplicate and average values were
calculated.
Where,
S= spredability
M= weight tied to upper slide.
L= length of glass slide.
T= time taken to separate the slides completely.
Extrudability Study [tube test]: It is calculated by the force required to extrude the emulgel
from the tube. The method applied for determination of applied shear in the region of the
rheogram corresponding to a shear rate exceeding the yield value and exhibiting consequent
plug flow. In this study emulgel extruded from lacquered aluminum collapsible tube on
application of weight in grams required to extrude at least 0.5cm ribbon of emulgel in 10
seconds. For better extrudability, more quantity is extruded. For the measurement of
extrudability, it is done in triplicate and the average values are calculated. The extrudability is
then calculated by using the following formula.
Extrudability = weight applied to extrude emulgel from tube (in gm) / Area (in cm2).
Rheological Studies: Viscosity of emulgel is determined at 25°C using a cone and plate
viscometer with spindle 52 and connected to a thermostatically controlled circulating water
bath.
Procedure: Accurately weighed 1g of emulgel was placed between these two slides
containing hair less fresh rat skin pieces, extra weight from the left pan was removed to
sandwitch the two pieces of glass and some pressure was applied to remove the presence of
air. The balance was kept in the position for 5 min. weight was added slowly at 200mg/min to
the left hand pan until the two glass slides got detached from each others. The weight
required to detach the emulgel from the glass surface gives the measure of bioadhesive
strength by using a formula,
Bioadhesive strength=weight required (in g) / area(cm2)
Skin Irritation Test (Patch Test): For this study emulgel is applied on the shaven skin of rat
and its adverse effect like change in color, change in skin morphology are evaluated up to 24
hours. About 8 rats can be used for the study. Test passes if no irritation shown. If it fails the
test is repeated with another 2 rats.
Microbiological assay: Microbiological assay was performed by using ditch plate technique.
Previously prepared Sabouraud’s agar dried plates were used. 3 grams of the gellified
emulsion are placed in a ditch cut in plate. Freshly prepared culture loops are streaked across
agar at a anglefrm the edge of the plate. After incubation for 18-24hrs at 25◦c, the fungal
growth was observed and the percentage inhibition was measured as follows
% inhibition = L2 /L1× 100
In-vitro Release Studies: The in vitro drug release studies were carried out using a modified
franz diffusion (FD) cell the formulation was applied on dialysis membrane which was
placed between donor and receptor compartment of the FD cell. Phosphate buffer PH 7.4 was
used as a donor and receptor compartment of the cell was maintained at 37c by circulating
water jacket. This whole assembly was kept on a magnetic stirrer and the solution was stirred
continuously using a magnetic bead. A similar bank set was run simultaneously as a control.
sample (5 ml) was withdrawn at suitable time intervals and replaced with equal amount of
fresh dissolution media. Samples were analysed spectrophotometrically at 318nm and
cumulative %drug release was calculated.
4 Physical Examination: The prepared ornidazole emulgel formulations when subjected for
colour appearance were transparent in carbapol 934, white viscous in HPMC K 100 and
brownish gummy in sodium alginate, creamy preparation with a smooth homogenous texture
and glossy appearance. Results have been discussed in table 8.
Table-Physical properties
S No Formulation Colour Phase Separation Grittiness Homogenicity Consistency
1 F1 White None - +++ +++
2 F2 White None - +++ +++
3 F3 White None - +++ +++
4 F4 Brownish gummy None - +++ +++
5 F5 Brownish gummy None - +++ +++
6 F6 Brownish gummy None - +++ +++
7 F7 Creamy None - +++ +++
8 F8 Creamy None - +++ +++
9 F9 Creamy None - +++ +++
Measurement of ph
The PH values of all the prepared formulation was ranging from 5.8- 6.0, which is considered
acceptable to avoid the risk of irritation upon application to the skin.
Spreadability Coefficient
The values of spreadability indicate that the emulgel is easily spreadable by small amount of
shear. Spreadability of F3 was 5.7cm/sec, indicating spreadability of emulgel containing
ornidazole was good as compound to marketed gel.
Table - Spreadability
S. No Formulation Diameter (CM)
1 F1 4.2
2 F2 4.8
3 F3 5.7
4 F4 4.1
5 F5 4.0
6 F6 4.9
7 F7 4.4
8 F8 4.1
9 F9 4.7
Rheological Studies
The viscosity of different emulgel formulations was determined at 250◦c using a brook field
viscometer. The emulgels were rotated at 10 (min) and 100 (max) rotations per minute with
spindle 4.
Swelling Index: The swelling index of different formulations was observed and the data was
shown in Table n.o. 12.
Determination of Drug Content: Drug content of each formulation was determined and data
was shown in table n.o11. As shown in the tablet of drug content uniformly. The drug content
uniformity of all the formulations was found to be ranging from 80% to 95% was observed
that as the concentration of emulsifying agent increasing the drug content increased.
Skin Irritation Test: No allergic symptoms like inflammation, redness, irritation appeared
on rats up to 24hrs.
In Vitro Drug Release: The cumulative % drug release profile of the formulation batches
has been shown in Table- 14 and as shown in table of in vitro release studies, the release
profile increases with increase in the concentration of emulsifier. From the emulgel
formulations carbapol 934 (F3) showed high amount of drug release. i.e. (92%) in 6 hrs. in
vitro cumulative % drug release data of formulations was shown in table n.o 14.
Time (min) F4 F5 F6
0 0.00 0.00 0.00
60 27 20 28
120 40 31 50
180 55 45 59
240 69 78 75
300 78 62 78
360 80 72 88
Time (min) F7 F8 F9
0 0.00 0.00 0.00
60 24 25 28
120 38 45 47
180 34 48 39
240 60 70 69
300 73 63 80
360 80 78 89
CONCLUSSION
The present study was to increase the penetration of the drug into the skin. In coming years,
the topical drug delivery will be used extensively to improve better patient compliance. In
present study ornidazole topical emulgels were prepared by using different polymers such as
carbopol 934, HPMC, sodium alginate as a polymers and liquid paraffin clove oil and mentha
oil and tween 80 used as an emulsifier, propylene glycol as a penetration enhancer. In this
study all the formulations were subjected to various evaluation parameters such as physical
appearance, pH evaluation, spreadability, swelling index, Rheological studies, drug content
and in vitro drug release were found to be within the limits\among all the formulations
formulated ornidazole topical emulgel containing carbopol 934 as a polymer and liquid
paraffin as a oil shows 93.2% drug release so we can concluded that F3 formulation was the
best formulations.
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