NASAL PREPARATIONS

(Ph. Eur. monograph 0676)

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

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Nasal preparations are liquid, semi-solid or solid preparations intended for administration to the nasal cavities to obtain a systemic or local effect. They contain one or more active substances. Nasal preparations are as far as possible non-irritating and do not adversely affect the functions of the nasal mucosa and its cilia. Aqueous nasal preparations are usually isotonic and may contain excipients, for example, to adjust the viscosity of the preparation, to adjust or stabilise the pH, to increase the solubility of the active substance, or to stabilise the preparation.

Nasal preparations are supplied in multidose or single-dose containers, provided, if necessary, with a suitable administration device, which may be designed to avoid the introduction of contaminants.

Unless otherwise justified and authorised, aqueous nasal preparations supplied in multidose containers contain a suitable antimicrobial preservative in an appropriate concentration, except where the preparation itself has adequate antimicrobial properties.

Where applicable, the containers 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 nasal preparations may be distinguished:

• — nasal drops and liquid nasal sprays;

• — nasal powders;

• — semi-solid nasal preparations;

• — nasal washes;

• — nasal sticks.

During the development of a nasal preparation whose formulation contains an antimicrobial preservative, 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 the text on Efficacy of antimicrobial preservation (5.1.3).

In the manufacture, packaging, storage and distribution of nasal preparations, suitable measures are taken to ensure their microbial quality; recommendations on this aspect are provided in the text on Microbiological quality of pharmaceutical preparations (5.1.4).

Sterile nasal 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 the text on Methods of preparation of sterile products (5.1.1).

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

Where the label states that the preparation is sterile, it complies with the test for sterility.

If the preparation is sterile, store in a sterile, airtight, tamper-proof container.

The label states:

• — the name of any added antimicrobial preservative;

• — where applicable, that the preparation is sterile.

Nasal drops and liquid nasal sprays are solutions, emulsions or suspensions intended for instillation or spraying into the nasal cavities.

Emulsions may show evidence of phase separation but are easily redispersed on shaking. Suspensions may show a sediment, which is readily dispersed on shaking to give a suspension that remains sufficiently stable to enable the correct dose to be delivered.

Nasal drops are usually supplied in multidose containers provided with a suitable applicator.

Liquid nasal sprays are supplied in containers with atomising devices or in pressurised containers fitted with a suitable adapter and with or without a metering dose valve, which comply with the requirements of the monograph on Pressurised pharmaceutical preparations (0523).

The size of droplets of the spray is such as to localise their deposition in the nasal cavity.

Unless otherwise prescribed or justified and authorised, nasal drops supplied in single-dose containers and single doses of metered-dose nasal sprays, both intended for systemic action, comply with the following tests.

Nasal drops in single-dose containers comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the test for uniformity of mass or 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.

Nasal drops that are solutions comply with the following test. Weigh individually the contents of 10 containers emptied as completely as possible, and determine the average mass. Not more than 2 of the individual masses deviate by more than 10 per cent from the average mass, and none deviate by more than 20 per cent.

Nasal drops that are suspensions or emulsions comply with the following test. Empty each container as completely as possible and carry out the test on the individual contents. They comply with test B for uniformity of content.

Metered-dose nasal sprays comply with the test for uniformity of dosage units (2.9.40) or, where justified and authorised, with the test for uniformity of mass or the test for uniformity of delivered dose shown below. Herbal drugs and herbal drug preparations present in the dosage form are not subject to the provisions of this paragraph.

In the case of metered-dose nasal sprays that are solutions, proceed as follows. Discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. Weigh the container, discharge once to waste and weigh the container again. Calculate the difference between the 2 masses. Repeat the procedure for a further 9 containers. Determine the mass variation (2.9.40).

In the case of metered-dose nasal sprays that are suspensions or emulsions, proceed as follows. Use an apparatus capable of quantitatively retaining the dose leaving the actuator of the atomising device. Shake the container for 5 s and discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. After 2 s, fire 1 dose of the metered-dose nasal spray into the collecting vessel by actuating the atomising device. Collect the contents of the collecting vessel by successive rinses. Determine the content of active substance in the combined rinses. Repeat the procedure for a further 9 containers. Determine the content uniformity (2.9.40).

Metered-dose nasal sprays that are solutions comply with the following test. Discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. Weigh the container, discharge once to waste and weigh the container again. Calculate the difference between the 2 masses. Repeat the procedure for a further 9 containers.

The preparation complies with the test if not more than 2 of the individual values deviate by more than 25 per cent from the average value and none deviate by more than 35 per cent.

Metered-dose nasal sprays that are suspensions or emulsions comply with the following test. Use an apparatus capable of quantitatively retaining the dose leaving the actuator of the atomising device. Shake the container for 5 s and discharge once to waste. Wait for a minimum of 5 s, shake for 5 s and discharge again to waste. Repeat this procedure for a further 3 actuations. After 2 s, fire 1 dose of the metered-dose nasal spray into the collecting vessel by actuating the atomising device. Collect the contents of the collecting vessel by successive rinses. Determine the content of active substance in the combined rinses. Repeat the procedure for a further 9 containers.

Unless otherwise justified and authorised, the preparation complies with the test if not more than 1 of the individual contents is outside the limits of 75 per cent to 125 per cent and none are outside the limits of 65 per cent to 135 per cent of the average content.

If 2 or at most 3 individual contents are outside the limits of 75 per cent to 125 per cent but within the limits of 65 per cent to 135 per cent, repeat the test for 20 more containers. The preparation complies with the test if not more than 3 individual contents of the 30 individual contents are outside the limits of 75 per cent to 125 per cent and none are outside the limits of 65 per cent to 135 per cent of the average content.

Nasal powders are powders intended for insufflation into the nasal cavity by means of a suitable device.

They comply with the requirements of the monograph on Powders for cutaneous application (1166).

The size of the particles is such as to localise their deposition in the nasal cavity and is verified by adequate methods of particle-size determination.

Semi-solid nasal preparations comply with the requirements of the monograph on Semi-solid preparations for cutaneous application (0132).

The containers are adapted to deliver the product to the site of application.

Nasal washes are generally aqueous isotonic solutions intended to cleanse the nasal cavities.

Nasal washes intended for application to injured parts or prior to a surgical operation are sterile.

During development, it must be demonstrated that the nominal content can be withdrawn from the container, for nasal washes presented in single-dose containers.

Nasal sticks comply with the monograph on Sticks (1154).

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