EYE PREPARATIONS

(Ph. Eur. monograph 1163)

Eye Preparations comply with the requirements of the European Pharmacopoeia. These requirements are reproduced below.

Ph Eur

Eye preparations are sterile liquid, semi-solid or solid preparations intended for administration upon the eyeball and/or to the conjunctiva, or for insertion in the conjunctival sac.

Where applicable, containers for eye preparations comply with the requirements of materials used for the manufacture of containers (3.1 and subsections) and containers (3.2 and subsections).

Several categories of eye preparations may be distinguished:

• — eye drops;

• — eye lotions;

• — powders for eye drops and powders for eye lotions;

• — semi-solid eye preparations;

• — ophthalmic inserts.

During the development of an eye preparation whose formulation contains an antimicrobial preservative, the necessity for and the efficacy of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable test method together with criteria for judging the preservative properties of the formulation are provided in chapter 5.1.3. Efficacy of antimicrobial preservation.

Eye preparations are prepared using materials and methods designed to ensure sterility and to avoid the introduction of contaminants and the growth of micro-organisms; recommendations on this aspect are provided in chapter 5.1.1. Methods of preparation of sterile products.

In the manufacture of eye preparations containing dispersed particles, measures are taken to ensure a suitable and controlled particle size with regard to the intended use.

During development, it must be demonstrated that the nominal contents can be withdrawn from the container of liquid and semi-solid eye preparations supplied in single-dose containers.

Eye preparations comply with the test. Applicators supplied separately also comply with the test. Remove the applicator with aseptic precautions from its package and transfer it to a tube of culture medium so that it is completely immersed. Incubate and interpret the results as described in the test.

Unless otherwise justified and authorised, store in a sterile, tamper-proof container.

The label states the name of any added antimicrobial preservative.

Eye drops are sterile aqueous or oily solutions, emulsions or suspensions of one or more active substances intended for instillation into the eye.

Eye drops may contain excipients, for example, to adjust the tonicity or the viscosity of the preparation, to adjust or stabilise the pH, to increase the solubility of the active substance, or to stabilise the preparation. These substances do not adversely affect the intended medicinal action or, at the concentrations used, cause undue local irritation.

Aqueous preparations supplied in multidose containers contain a suitable antimicrobial preservative in appropriate concentration except when the preparation itself has adequate antimicrobial properties. The antimicrobial preservative chosen must be compatible with the other ingredients of the preparation and must remain effective throughout the period of time during which eye drops are in use.

If eye drops do not contain antimicrobial preservatives they are supplied in single-dose containers or in multidose containers preventing microbial contamination of the contents after opening.

Eye drops intended for use in surgical procedures do not contain antimicrobial preservatives.

Eye drops that are solutions, examined under suitable conditions of visibility, are practically clear and practically free from particles.

Eye drops that are suspensions may show a sediment that is readily redispersed on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be delivered.

Multidose preparations are supplied in containers that allow successive drops of the preparation to be administered. The containers contain at most 10 mL of the preparation, unless otherwise justified and authorised.

Unless otherwise justified and authorised, eye drops in the form of a suspension comply with the following test: introduce a suitable quantity of the suspension into a counting cell or with a micropipette onto a slide, as appropriate, and scan under a microscope an area corresponding to 10 µg of the solid phase. For practical reasons, it is recommended that the whole sample is first scanned at low magnification (e.g. × 50) and particles greater than 25 µm are identified. These larger particles can then be measured at a larger magnification (e.g. × 200 to × 500). For each 10 µg of solid active substance, not more than 20 particles have a maximum dimension greater than 25 µm, and not more than 2 of these particles have a maximum dimension greater than 50 µm. None of the particles has a maximum dimension greater than 90 µm.

The label states, for multidose containers, the period after opening the container after which the contents must not be used. This period does not exceed 4 weeks, unless otherwise justified and authorised.

Eye lotions are sterile aqueous solutions intended for use in rinsing or bathing the eye or for impregnating eye dressings.

Eye lotions may contain excipients, for example to adjust the tonicity or the viscosity of the preparation or to adjust or stabilise the pH. These substances do not adversely affect the intended action or, at the concentrations used, cause undue local irritation.

Eye lotions supplied in multidose containers contain a suitable antimicrobial preservative in appropriate concentration except when the preparation itself has adequate antimicrobial properties. The antimicrobial preservative chosen is compatible with the other ingredients of the preparation and remains effective throughout the period of time during which the eye lotions are in use.

If eye lotions do not contain antimicrobial preservatives, they are supplied in single-dose containers. Eye lotions intended for use in surgical procedures or in first-aid treatment do not contain an antimicrobial preservative and are supplied in single-dose containers.

Eye lotions, examined under suitable conditions of visibility, are practically clear and practically free from particles.

The containers for multidose preparations do not contain more than 200 mL of eye lotion, unless otherwise justified and authorised.

The label states:

• — where applicable, that the contents are to be used on one occasion only;

• — for multidose containers, the period after opening the container after which the contents must not be used; this period does not exceed 4 weeks, unless otherwise justified and authorised.

Powders for the preparation of eye drops and eye lotions are supplied in a dry, sterile form to be dissolved or suspended in an appropriate liquid vehicle at the time of administration. They may contain excipients to facilitate dissolution or dispersion, to prevent caking, to adjust the tonicity, to adjust or stabilise the pH or to stabilise the preparation.

After dissolution or suspension in the prescribed liquid, they comply with the requirements for eye drops or eye lotions, as appropriate.

Single-dose powders for eye drops and eye lotions comply with the test or, where justified and authorised, with the tests for uniformity of content and/or uniformity of mass shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.

Unless otherwise prescribed or justified and authorised, single-dose powders for eye drops and eye lotions with a content of active substance less then 2 mg or less than 2 per cent of the total mass comply with test B. If the preparation has more than one active substance, the requirement applies only to those substances that correspond to the above condition.

Single-dose powders for eye drops and eye lotions comply with the test. If the test for uniformity of content is prescribed for all the active substances, the test for uniformity of mass is not required.

Semi-solid eye preparations are sterile ointments, creams or gels intended for application to the conjunctiva or to the eyelids. They contain one or more active substances dissolved or dispersed in a suitable basis. They have a homogeneous appearance.

Semi-solid eye preparations comply with the requirements of the monograph Semi-solid preparations for cutaneous application (0132). The basis is non-irritant to the conjunctiva.

Semi-solid eye preparations are packed in small, sterilised collapsible tubes fitted or provided with a sterilised cannula. The containers contain at most 10 g of the preparation, unless otherwise justified and authorised. The tubes must be well-closed to prevent microbial contamination. Semi-solid eye preparations may also be packed in suitably designed single-dose containers. The containers, or the nozzles of tubes, are of such a shape as to facilitate administration without contamination.

Semi-solid eye preparations containing dispersed solid particles comply with the following test: spread gently a quantity of the preparation corresponding to at least 10 µg of solid active substance as a thin layer. Scan under a microscope the whole area of the sample. For practical reasons, it is recommended that the whole sample is first scanned at a small magnification (e.g. × 50) and particles greater than 25 µm are identified. These larger particles can then be measured at a larger magnification (e.g. × 200 to × 500). For each 10 µg of solid active substance, not more than 20 particles have a maximum dimension greater than 25 µm, and not more than 2 of these particles have a maximum dimension greater than 50 µm. None of the particles has a maximum dimension greater than 90 µm.

The label states, for multidose containers, the period after opening the container after which the contents must not be used. This period does not exceed 4 weeks, unless otherwise justified and authorised.

Ophthalmic inserts are sterile, solid or semi-solid preparations of suitable size and shape, designed to be inserted in the conjunctival sac, to produce an ocular effect. They generally consist of a reservoir of active substance embedded in a matrix or bounded by a rate-controlling membrane. The active substance, which is more or less soluble in lacrymal liquid, is released over a determined period of time.

Ophthalmic inserts are individually distributed into sterile containers.

In the manufacture of ophthalmic inserts, measures are taken to ensure a suitable dissolution behaviour.

Ophthalmic inserts comply with the test or, where justified and authorised, with the test for uniformity of content shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.

Ophthalmic inserts comply, where applicable, with test A.

The label states:

• — where applicable, the total quantity of active substance per insert;

• — where applicable, the dose released per unit time.

Ph Eur