Ophthalmic preparations: General introduction, types of ophthalmic preparations, requirements for ophthalmic preparation and MCQs for GPAT, NIPER, Pharmacist and Drug Inspector exam

Ophthalmic preparations are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside the eye (intraocular) or adjacent to it (periocular, e.g., juxtascleral or subtenon), or used in conjunction with an ophthalmic device.

Types of ophthalmic dosage forms:

Ophthalmic solutions – These are by far the most common dosage forms for delivering drugs to the eye. By definition, ingredients are completely soluble such that dose uniformity is not an issue, and there is little physical interference with vision.

Powders for solutions – Drugs that have very limited stability in aqueous solution can sometimes be prepared as sterile powders for reconstitution by the pharmacist before dispensing to the patient. The sterile powder should be aseptically reconstituted with the accompanying sterile diluent that has been optimized for dissolution, preservation, and stability. The pharmacist must convey to the patient any special storage instructions, including the expiration date.

Ophthalmic suspensions – Suspensions are dispersions of finely divided, relatively insoluble drug substances in an aqueous vehicle containing suitable suspending and dispersing agents. The vehicle is, among other things, a saturated solution of the drug substance. Because of a tendency of particles to be retained in the cul-de-sac, the contact time and duration of action of a suspension could theoretically exceed that of a solution. The drug is absorbed from solution, and the solution concentration is replenished from retained particles. Each of these actions is a function of particle size, with solubility rate being favored by smaller size and retention favored by a larger size; thus, optimum activity should result from an optimum particle size.

Gel-forming solutions – Ophthalmic solutions (usually water-based), which contain a polymer system that is a low-viscosity liquid in the container but gels on contact with the tear fluid, have increased contact time and can provide increased drug absorption and prolonged duration of therapeutic effect. The liquid-to-gel phase transition can be triggered by a change in temperature, pH, ionic strength, or presence of tear proteins, depending on the particular polymer system employed. Timolol maleate gel-forming solutions formulated with specific patented gellan or xanthan gums have clinically demonstrated prolonged duration of IOP lowering, such that their dosing frequency can be reduced from twice to once a day. Review the labeling for commercial gel-forming solutions before dispensing for current instructions related to patient administration.

Ophthalmic Ointments – Ophthalmic ointments are primarily anhydrous and contain mineral oil and white petrolatum as the base ingredients, the proportions of which can be varied to adjust consistency and the melting temperature. Dosage variability probably is greater than with solutions (though probably no greater than that with suspensions).

Ophthalmic emulsions – An emulsion dosage form offers the advantage of the ability to deliver a poorly water-soluble drug in a solubilized form as an eyedrop. The drug is dissolved in a nonaqueous vehicle, such as castor oil, and emulsified with water, using a nonionic surfactant and, if needed, an emulsion stabilizer. An emulsion with water as the external phase can be less irritating and better tolerated by the patient than use of a purely nonaqueous vehicle. Such an emulsion is used to deliver cyclosporine topically for the treatment of chronic dry eye conditions.

Ophthalmic gels – Gel-forming polymers, such as carbomer, have been used to develop aqueous, semisolid dosage forms, which are packaged and administered the same as ointments. The viscous gels have significantly increased topical residence time and can increase drug bioavailability and decrease dosage frequency, compared to solutions. Although they contain a large proportion of water, they can still cause blurring of vision. A carbomer gel of pilocarpine administered at bedtime has been shown to prolong the IOP-lowering effect in patients for up to 24 hours.

Ocular Inserts – Ocular inserts have been developed in which the drug is delivered on the basis of diffusional mechanisms. Such a solid dosage form delivers an ophthalmic drug at a near constant known rate, minimizing side effects by avoiding excessive absorption peaks. The delivery of pilocarpine by such an insert was commercialized in 1975 (Ocusert Pilo) by Alza Corporation. The Ocusert is designed to be placed in the lower cul-de-sac to provide a weekly dose of pilocarpine, at which time the system is removed and replaced by a new one. The near zero-order rate delivery is based on the selection of a non-eroding co-polymer membrane enclosing the drug reservoir.

Requirements:

Foreign particles: All the opthalmic products should be clear and free from foreign particles, fibers and filaments. Opthalmic solutions should be clarified very carefully by passing through bacteria proof filters such as membrane filters, sintered glass filters. The particle size of the eye suspension should be in an ultrafine state of subdivision to minimize irritation. A separate filter should be used for different opthalmic products in order to avoid the contamination.

Viscosity: In order to prolong the contact time of the drug in the eye, various thickening agents are added in the opthalmic preparations. Polyvinyl alcohol (1-4%), polyethylene glycol, methyl cellulose, carboxy methyl cellulose are some of the commonly used thickening agents. These agents improve the viscosity of the preparation. An ideal thickening agent should possess the following properties:

• It should be easy to filter.
• It should be easy to sterilize.
• It should be compatible with other ingredients.
• It should possess requisite refractive index and clarity level.

Thickening agents are not included in the formulation of eye drops and eye lotions which are required to be used during or after surgery due to some possible adverse effects on the interior of the eye.

Tonicity: Opthalmic products should be isotonic with lachrymal secretions to avoid discomfort and irritation.  It has been observed that eye can tolerate a range of tonicity from 0.5-2% NaCl. There are certain isotonic vehicles which are used to prepare opthalmic products like 1.9% boric acid, sodium acid phosphate buffer.

pH of the preparations: pH plays an important role in therapeutic activity, solubility, stability and comfort to the patient. Tears have a pH of about 7.4. eye can tolerate solution having wide range of pH provided they are not strongly buffered, since the tear will rapidly restore the normal pH value of the eye.  Alkaloid salt solutions are stable at pH 2-3 but this pH is irritant to eye. The alkaloids get precipitated at pH above 7 and creates a number of formulation problems.

Sterility: Opthalmic preparations must be sterile when prepared. Pseudomonas aeroginosa is very common gram –ve bacteria which is generally found to be present in opthalmic products. It may cause serious infections of cornea. It can cause complete loss of eye sight in 24-48 hrs. To maintain sterility in multi dose container, containing opthalmic products, a suitable preservative is added. The preservative should be non-toxic, non-irritant and should be compatible with medicaments. The opthalmic products are generally sterilized by autoclaving, filtration through bacteria proof filters and addition of bactericides at low temperature.

Surface activity: Vehicles used in opthalmic preparations must have good wetting ability to penetrate cornea and other tissues. Certain surfactants or wetting agents added which are found suitable for opthalmic products. It should not cause any damage to the tissue of eye. Benzalkonium chloride, polysorbate 20, polysoabate 80, dioctyl sodium sulpho succinate etc., are some of the surfactants which are commonly used.

Multiple choice questions:

1.Ophthalmic preparations are specialized dosage forms designed to be instilled

a)topically

b)intraocularly

c)periocularly

d)all of these

2.Ophthalmic preparations designed to be instilled onto the external surface of the eye are known as

a)topical preparations

b)intraocular preparations

c)periocular preparations

d)all of these

3.Ophthalmic preparations designed to be administered inside the eye are called as

a)topical preparations

b)intraocular preparations

c)periocular preparations

d)all of these

4.Which of the following is not a type of opthalmic dosage form?

a)Ophthalmic solutions

b)Ophthalmic suspensions

c)Implants

d)Gel-forming solutions

5.These are by far the most common dosage forms for delivering drugs to the eye.

a)Ophthalmic solutions

b)Ophthalmic suspensions

c)Powders for solutions

d)Gel-forming solutions

6.Drugs that have very limited stability in aqueous solution can be prepared as

a)Ophthalmic solutions

b)Ophthalmic suspensions

c)Powders for solutions

d)Gel-forming solutions

7.The liquid-to-gel phase transition in Gel-forming solutions can be triggered by

a)change in temperature

b)pH

c)ionic strength

d)all of these

8.Ophthalmic ointments are primarily anhydrous and contain contain mineral oil and white petrolatum as the base ingredients.

a)true

b)false

9.The viscous gels have significantly _____ topical residence time.

a)increased

b)decreased

c)stable

d)first increases then decreased

10.Ocusert Pilo delivers

a)Physostigmine

b)Pilocarpine

c)Epinephrine

d)Neostigmine

11.Opthalmic solutions should be clarified very carefully by passing through bacteria proof filters such as

a)membrane filters

b)sintered glass filters

c)filter candles

d)a and b

12.Which of the following is/are commonly used thickening agents used in opthalmic preparations?

a)polyethylene glycol

b)methyl cellulose

c)carboxy methyl cellulose

d)all of these

13.Eye can tolerate a range of tonicity from

a)0.5-1% NaCl

b)0.5-0.9% NaCl

c)0.5-2% NaCl

d)1-2% NaCl

14.Tears have a pH of about

a)7.0

b)7.2

c)7.3

d)7.4

15.Which bacteria is generally found to be present in opthalmic products?

a)E. Coli

b)Pseudomonas aeroginosa

c)Staphylococcus species

d)Enterobacter

Solutions:

1. d)all of these
2. a)topical preparations
3. b)intraocular preparations
4. c)Implants
5. a)Ophthalmic solutions
6. c)Powders for solutions
7. d)all of these
8. a)true
9. a)increased
10. b)Pilocarpine
11. d)a and b
12. d)all of these
13. c)0.5-2% NaCl
14. d)7.4
15. b)Pseudomonas aeroginosa

References:

1. Remington Essential of Pharmaceutics, 1st edition 2013, page no. 541, 547-549.

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