Theory Industrial Pharmacy-I [PY3CO19T]

Odd Semester (Aug-Dec 2021)

Ophthalmic Preparation

Sourabh Billore
Faculty of Pharmacy
E mail: Sourabh.Billore@medicaps.ac.in
 Introduction
“They are specialized dosage forms designed to be instilled onto the external surface of
the eye (topical), administered inside (intraocular) or adjacent (periocular) to the eye or
used in conjunction with an ophthalmic device.”

The most commonly employed ophthalmic dosage forms are solutions, suspensions and
ointments.

Sourabh Billore Sourabh.billore@medicaps.ac.in

The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming solutions,
ocular inserts, intravitreal injections and implants.

The formulation of ophthalmic dosage forms requires safety to the eye,

availability, efficacy and pharmaceutical elegance, in addition to meeting the
applicable regulations.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

since the majority of ophthalmic drugs are water soluble. Solution
dosageformsarepreferredastheyareeasytoadminister.However,wherethedrughaslimitedw
ater solubility, or when a prolonged therapeutic action is required, disperse systems
such as suspensions, gelled systems and ointments are required.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Drugs Used in The Eye:
 Miotics e.g. pilocarpine Hcl
 Mydriatics e.g. Atropine
 Cycloplegics e.g. Atropine
 Anti-inflammatories e.g. corticosteroids
 Anti-infectives(antibiotics, antivirals and antibacterials)
 Anti-glucoma drugs e.g. pilocarpine Hcl
 Adjuncts e.g. Irrigating solutions

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Ideal Requirements:
1. Good corneal penetration.

2. Prolong contact time with corneal tissue.

3. Simplicity of instillation for the patient.

4. Non irritative and comfortable form

5. Appropriate rheological properties

6.Sterility, clarity, buffer, buffer capacity and pH, tonicity, viscosity, stability, comfort,
additives, particle size, packaging and preservatives

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Classification of Ophthalmic Products:

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Artificial Tears
Artificial tears are lubricant eye drops used to treat the dryness and irritation
associated with deficient tear production in Keratoconjunctivitis Sicca (dry eyes)

They are also used to moisten contact lenses and in eye examinations.

Artificial tears are supplemented with other treatments in moderate to severe

forms of dry eyes

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Preparations contain Carboxymethylcellulose, Polyvinyl alcohol, Hydroxypropyl
methylcellulose (a.k.a. HPMC or hypromellose), Hydroxypropylcellulose and
Hyaluronic acid (a.k.a. Hyaluronan, HA).

• They contain water, salts and polymers but lack the proteins found in natural
tears.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Additives
1. Buffer and adjust pH,

2. Stabilize the active ingredients against decomposition ,

3. Increase solubility,

4. Impart viscosity

5. Act as solvent

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Tonicity and Tonicity-Adjusting Agents
The term isotonic, meaning equal tone, is sometimes used interchangeably with
the term iso-osmotic.

Commonly tonicity adjusting ingredients include: NaCl, KCL, Buffer salts,

Dextrose, Glycerin, Propylene Glycol, Mannitol.

Lacrimal fluid is isotonic with blood having an isotonicity value corresponding

to that of 0.9% NaCl solution

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Stabilizers & Antioxidants:

Stabilizers are ingredients added to a formula to decrease the rate of decomposition of

the active ingredients.

Sodium bisulfite or metabisulfite are used in concentration up to 0.3% in epinephrine

hydrochloride and bitartrate solutions.

The several antioxidant system have been developed: These consists of ascorbic acid
and acetylcysteine and sodium thiosulfate .

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Surfactants

The order of surfactant toxicity is :

Anionic > Cationic >> Non-ionic

Several nonionic surfactants are used in relatively low concentration to aid in dispersing steroids in
suspensions and to achieve or to improve solution clarity.

Those principally used are the sorbitan ether esters of oleic acid ( Polysorbate or Tween 20 and 80 ).

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

 pH Adjustment and Buffers

pH adjustment is very important as pH affects

Eye irritation Increase in tear fluid secretion leads to Rapid loss of medication.

To enhance aqueous solubility of the drug.

Ideally, every product would be buffered to a pH of 7.4 (the normal physiological

pH of tear fluid ).

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Viscosity-Imparting Agents

Polyvinyl Alcohol, Methylcellulose, Hydroxypropyl Methylcellulose,

Hydroxyethylcellulose, and Carbomers, are commonly used to increase the viscosity of
solution and suspensions (to retard the rate of setting of particles).

They increase the ocular contact time, there by decreasing the drainage rate, increase
the mucoadhesiveness and Increasing the bioavailability .

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Vehicles

Purified water meeting USP standards may be obtained by:

Distillation, deionization or reverse osmosis

Oils have been used as vehicles for several topical eye drops products that are
extremely sensitive to moisture.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Manufacturing considerations
A. Manufacturing Environment

 The environment should be sterile and particle-free through

 Laminar-flow should be used throughout the manufacturing area.
  Relative humidity controlled to between 40 and 60%.
 Walls, ceilings and floors should be constructed of materials that are hard, non
Flaking, smooth and non-affected by surface cleaners or disinfectants.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

The blow /fill/seal method

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Ophthalmic Inserts
Ocular insert (Ocusert) are sterile preparation that prolong residence time of drug with a
controlled release manner and negligible or less affected by nasolacrimal drainage.

It shows diffusion controlled release

It consists of a central reservoir of drug enclosed in specially designed microporous

membrane allowing drug to diffuse from reservoir at precisely predetermined rate

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

CLASSIFICATION
1 .NON ERODIBLE INSERTS
 Ocusert

 Contact lens

2 .ERODIBLE INSERTS

i. Lacriserts

ii. SODI ((Soluble ocular drug inserts)

iii. Mindisc
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Ophthalmic inserts are defined as sterile solid or semisolid preparations, with a
thin, flexible and multilayered structure, for insertion in the conjunctival sac.

The insert is flexible & is a multilayered structure consisting of a drug containing

core surrounded on each side by a layer of copolymer membranes through which
the drug diffuses at a constant rate. The rate of diffusion is controlled by the
polymer composition, the membrane thickness & the solubility of the drug. The
devices (inserts) are sterile & do not contain preservatives.
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore
Advantages:
 Increasing contact time and improving bioavailability
 Providing a prolong drug release and thus a better efficacy
 Reduction of adverse effects
 Reduction of the number administrations and thus better patient compliance.

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

Insoluble / Non erodible inserts

Insoluble insert is a multilayered structure

consisting of a drug containing core
surrounded on each side by a layer of
copolymer membranes through which the
drug diffuses at a constant rate

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore

ERODIBLE INSERTS

The solid inserts absorb the aqueous tear fluid and gradually erode or
disintegrate. The drug is slowly leached from the hydrophilic matrix.

They quickly lose their solid integrity and are squeezed out of the eye with eye
movement and blinking

Sourabh.billore@medicaps.ac.in Medi-Caps University, Indore