FORMULATION OF OIL-BASED
EAR ANTI-INFECTIVE DROPS
BY
ANDI SRI SURIATI AMAL
Dosen Prodi Farmasi, Fakultas Ilmu Kesehatan
Universitas Darussalam Gontor
SEMINAR NASIONAL HASIL RISET DAN STANDARDISASI INDUSTRI IV
BANDA ACEH, 5 – 6 NOVEMBER 2014
Content
2
Introduction
Fact About Otic Anti-infective
Available Products List
Characteristics of Ideal Ear Drops
Objective
Method
Result: - Advantages & Limitation
- Practical Problems,
Quality and GMP
Conclusion
Introduction
3
Otitis externa, infection or inflammation
of the external ear canal, is one of the most
common diseases of the ear.
Otic preparations are commonly used to
treat diseases of the external ear and
occasionally of the middle ear.
The majority of the existing otic products
on the market are formulated as solution
dosage forms containing either a
combination of antibacterial and
anti-inflammatory agents or antifungal and
anti-inflammatory agents.
About otic preparation
4
Mostly use propylene glycol or
anhydrous glycerin as main solvent.
propylene glycol as solvent, which is
not only expensive but
also known to have OTOTOXIC
effects
5
NO PRODUCT INGREDIENTS MANUFACTURER
1. Betnesol-N® Betamethasone sod. Phosphate 0.1 %, Neomycin sulphate 0.5 %
UCB Pharma (BNF)
2. Otosporin Polymyxin B. sulphate 10000 U/G, Neomycin sulphate 3400 U/G, Hydrocortisone 1.0 % w/w
GSK (BNF)
3. Vistamethasone-N® Betamethasone sod. Phosphate 0.1 %, neomycin sulphate 0.5%.
Martindale (BNF)
4. Otomize® Dexamethazone 0.1 %, neomycin sulphate 3250 units/mL, glacial acetic acid 2 %.
GSIC Consumer Healthcare (BNF)
5. Sofradex Dexamethazone 0.05%, framycetin sulphate 0.5%, gramicidin 0.005%
Sanovi-Aventis (BNF)
6. Locorten-Vioform® Flumetasone pivalate 0.2%, clioguinol 1 % Amdipharm (BNF)
7. Gentisone® Hydrocortisone acetate 1 %, gentamycin 0.5 % Amdipharm (BNF)
8. Predsol-N® Prednisolone sod. Phosphate 0.5 %, neomycin sulphate 0.5 %
UCB Pharma (BNF)
Table: Ear anti-infective drops available in the
Characteristics of Ideal Vehicle for Ear Drops
6
softens cerumen
emollient properties
inert
non-irritant
viscous vehicle
prolonged contact of the active ingredients
with the surface of the ear canal
Objective
7
To develop and formulate a new product
containing clotrimazole and triamcinolone
acetonide in one single oil-based
preparation that can be used for treating
antifungal and anti-inflammatory ear
Method
8
Stability study
Analytical method
development
Drug-excipients compatibility
Solubility characteristics
of the drugs
Physicochemical characteristics
of the drug
Result
9
DIFFERENT FORMULATIONS OF ANTI-INFECTIVE DROPS FOR THE
EAR
Formula Clotrima
zole
%
Triamcin
olone
%
Slv for
Clot.
%
Slv for
Triam.
%
Coconut
oil
%
Refined
palm
olein %
Olive oil
%
A
1
0.1
10
10
Up to
100%
-
-B
1
0.1
10
10
-
Up to
100%
-C
1
0.1
10
10
-
-
Up to
100%
Chemical Structure
10
Triamcinolone acetonide (C
24H
31FO
6)
Clotrimazole (C
22H
17ClN
2)
Triamcinolone acetonide was
halogenated corticosteriod to
be widely used topically and
was found to be therapeutically
effective for psoriasis
Clotrimazole, is known to be active
against a broad spectrum of
pathogenic fungi, but is also
effective for treating systemic
blas-tomycosis, candidiasis,
cocci-dioidomycosis, histoplasmosis and
paracoccidioidomycosis.
Advantages of This New Product
11
Meet all the criteria of an ideal
ear drops preparation.
Lower cost
For example: coconut oil, costs only
RM 6.48 per 100ml, olive oil RM
7.87 per 100ml the price of
propylene glycol is almost triple
(RM 18 per 100ml)
Advantages of This New Product
12
All the solvents were more natural in terms of its
availability in local markets such as coconut oil &
palm oil.
Harmless to the skin when compared with
propylene glycol, which is known for its ototoxicity
effect.
Limitation
13
Most antimicrobials, fungal and
anti-inflammatory are water soluble.
More difficult to make this preparation of oil-based
Result
14
Practical Problems
The major challenge in developing these new otic
preparations containing two or more active
components were:
1.
To choose a solvent in which the two ingredients
can dissolve since the two drugs chosen have
different solubility profiles.
2.
To find the solvent that can mix up with the oil as
Result
15
Quality and GMP (USP 23 (1997))
1. Evaluation of formulation like
density, viscosity, pH and clarity had
been checked.
2. This formula showed the specified
high standards of quality, with its
active and non-active ingredients
being chemically and physically
compatible.
Physicochemical properties of product
16
Formula/Test
A
B
C
USP 23 (1993)
pH
5.97
6.01
5.96
5.0 – 7.2
(pH of the normal skin of the external auditory canal)
Density
0.9091
0.9111
0.9097
± 1.0000
Viscosity (cps)
6.8045
10.0674
10.5416
10 - 30
Formula A using coconut oil as main solvent
Formula B using refined palm olein as main solvent
Formula C using olive oil as main solvent
Result
17
CHROMATOGRAM OF TRIAMCINOLONEACETONIDE,
CLOTRIMAZOLE AND PROGESTERONE
( Analysis of active ingredients using high performance liquid chromatography
Accuracy, Recovery and coefficient of variation of analysis of
clotrimazole and triamcinolone in the new anti-infective drops
preparation (n=6) using HPLC method
18
Sample Active Ingredient Expected value (µg)
Value obtained (µg)
Inaccuracy (%) Recovery (%) Coefficient of variation (%) A Triamcinolone Clotrimazole 4 10 15 40 100 150 4.2732 9.7800 15.0500 40.2732 79.0800 123.7920 7.57 2.23 1.09 7.57 20.92 17.52 106.23 97.77 99.95 106.83 79.08 82.39 8.1 0.8 2.5 8.1 1.9 1.3 B Triamcinolone Clotrimazole 4 10 15 40 100 150 4.9272 10.0145 15.3603 32.2403 87.5412 123.9250 23.18 0.62 2.40 0.19 12.46 4.30 123.75 100.15 102.40 80.60 87.54 95.70 1.0 0.9 0.6 4.6 2.5 1.2 C Triamcinolone Clotrimazole 4 10 15 40 100 150 4.9272 10.0145 15.3603 40.9272 94.0145 150.3603 23.18 0.62 2.40 2.32 6.06 0.24 123.18 100.16 102.40 102.32 94.02 100.24 1.03 0.97 0.64 1.03 5.03 0.06
USP 23 (1993), recovery test for topical solution should contain not less than 90.0% and not more than 115.0 % of the labeled amount of triamcinolone acetonide and for clotrimazole should not less than 90.0% and not more than 115.0%.
