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FORMULATION AND EVALUATION OF OPHTHALMIC FILMS FOR CONTROLLED
RELEASE OF TIMOLOL MALEATE
1K.S.Rathore, 2S.S.Sisodia, 3R.K.Nema1B.N.Girls College of Pharmacy, Udaipur, 2B.N. College of Pharmacy, Udaipur and 3Rishiraj College of Pharmacy, Indore-MP
Presented at –
Pharmanext International Pharmacy Conference, The Grand Neelam, Calangute, Goa
Structure of eye
The ophthalmic preparations are available as- -sterile,
-buffered, -isotonic solution.
Several types of dosage forms are applied as the delivery system for the ocular delivery of drugs. The most prescribed dosage forms are- - the eye drop solution as drops are easier to administer. - Suspensions, - gelled systems, - ointment are also used for prolonged therapeutic action.But these are primordial and inefficient
Characteristics of ophthalmic preparations
Should be- •non-irritating to the ocular tissue.•homogenous i.e, particles uniformly dispersed, smooth & free from lumps or agglomerates.
•Relatively non-greasy.•Should not cause blurred vision.•Should not cause intolerable foreign body sensation.
•Sterile & adequately preserved.•Physically & chemically stable.•Efficacious.
Problems with conventional ophthalmic dosage forms
•Drainage of the instilled solution;•Lachrimation and tear turnover;•Metabolism;•Tear evaporation;•Non-productive absorption/ adsorption;•Limited corneal area and poor corneal
permeability; and•Binding of the lachrymal proteins.
The following recent trends are in vogue: Polymer based delivery plans
• Mucoadhesive dosage forms• Ocular films or Inserts• Collagen shields• Drug presoaked hydrogel type contact lens
and pledgets- Ocufit®, Minidisc®, SODI®,NODS®, Lacrisert® etc.
• Ocular Iontophoresis• Phase Transition systems• Microspheres and Nanoparticles• Chemical delivery systems vesicular
systems.
Advantages with ocular films such as:
•Accurate dosing•Capacity to provide at constant rate and
prolong drug release thus a better efficacy.• Increasing contact time and thus improving
bioavailability.•Possible reduction of systemic absorption
and thus reduced systemic adverse effects.
In common disorders•Astigmatism•Blepharitis•Blurred vision•Cataract•Corneal ulcer•Glaucoma•Hyperopia•Myopia•Photokeratitis•Retinitis pigmentosa etc.
Ocular films are prospective for future
Glaucoma A group of diseases with-
*characteristic optic nerve damage.*visual field loss.*elevated IOP (>22mmHg) ; variable
in early stage often asymptomatic (Insidious in nature);.Damage is irreversible.Effective treatment is available. Glaucoma is sometimes called the silent thief of sight because it can slowly steal our sight before we realize anything's wrong. It's a leading cause of vision loss.
Plan of work
•Timolol maleate-as experimental drug•Hypromellose, PVA as polymers.•PEG and Glycerine used as plasticizers.•Gluteraldehyde for hardened effect.•Solvent casting technology used for ocular
films formulation•The main purpose of the study was to
transport the drug into zero-order kinetics
Materials and Methods•Preformulation study•Standard curve.•Artificial Tear Fluid• In-vitro and in-vivo studies
OH
O
SN
N
N
O
NH
O
OH
O
OH
.
Timolol maleate
β- adrenergic blocker which is non-selective between beta-1 and beta-2 (β-1 and β-2) adrenergic receptors
reduces IOP by reducing aqueous humor production or possibly outflow
S. No. Ingredients Quantity
1 Sodium chloride 0.670g
2 Sodium
bicarbonate
0.200g
3 Calcium
chloride.2H2O
0.008g
4 Purified water q.s. to 100g
Composition of Simulated Tear Fluid (Rozier et al., 1989)
Preparation of ocular films with timolol maleate
Ingredients
%(w/v)Formulations
Timolol maleate
HPMC+
PVA
Glycerin+
PEG BAK
Distilled water q.s.
TF-1 0.5%
16%
70% 0.002% 100 ml
TF-2 0.5% 50% 0.002% 100 ml
TF-3 0.5% 40% 0.002% 100 ml
TF-4 0.5%
18%
70% 0.002% 100 ml
TF-5 0.5% 50% 0.002% 100 ml
TF-6 0.5% 40% 0.002% 100 ml
TF-7 0.5%
20%
70% 0.002% 100 ml
TF-8 0.5% 50% 0.002% 100 ml
TF-9 0.5% 40% 0.002% 100 ml
Calibration curve of timolol maleate
0 10 20 30 40 50 600
0.2
0.4
0.6
0.8
1
1.2
f(x) = 0.0211127223636364 x + 0.0446666954545456R² = 0.989732273524793
Concentration in µg/ml
Abs
orba
nce
•
Evaluations of ocular films of timolol maleate as:*Thickness of the film*Uniformity of the weight*Content uniformity*Percentage moisture absorption*Percentage moisture loss*Tensile strength
FTIR spectra of drug and film
IR spectra of film
DSC of drug and films
Drug content of hardened ocular films with different concentration of PEG and glycerine
f1 f2 f3 f4 f5 f6 f7 f81.95
1.955
1.96
1.965
1.97
1.975
1.98
1.985
1.99
1.995
2
R1R2
R3R4
R5
R1 R2
R3 R4
R5
Formulations
Dru
g co
nten
t
In comparison with the traditional ophthalmic preparations (eye drops) ocular films present advantages such as-A. Increasing in contact time and thus improving bio-availability.B. Possibility of providing a prolonged drug release and hence better efficacy.C. Reduction of systemic side effects and thus reduced adverse effects. D. Reduction of the number of administrations and hence better patient compliance.E. Administration of an accurate dose in the eye and thus a better therapy.
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