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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