Daarnaast worden voor de afzonderlijke geneesmiddelvormen eisen geformuleerd in:
Weigh individually twenty units taken at random or, for single-dose preparations presented in individual containers, the contents of twenty units, and determine the average mass. Not more than two of the individual masses deviate from the average mass by more than the percentage deviation shown in Table 2.9.5.-1 and none deviates by more than twice that percentage.
pharmaceutical Form
Average Mass
Percentage
Deviation
Tablets (uncoated and film-coated)
80 mg or less
10
Tablets (uncoated and film-coated)
more than 80 mg and
less than 250 mg
7.5
Tablets (uncoated and film-coated)
250 mg or more
5
Capsules, Granules (uncoated, single-dose) and
Powders (single-dose)
Less than 300 mg
10
Capsules, Granules (uncoated, single-dose) and
Powders (single-dose)
300 mg or more
7.5
Powders for parenteral use
more than 40 mg
10
Suppositories and Pessaries
all masses
5
(*) When the average mass is equal to or below 40 mg, the preparation is not submitted to the test for uniformity of mass but to the test for uniformity of content of single-dose preparations (2.9.6).
For capsules and powders for parental use, proceed as described below.
CAPSULES: Weigh an intact capsule. Open the capsule without losing any part of the shell and remove the contents as completely as possible.
For soft shell capsules, wash the shell with ether or other suitable solvent and allow to stand until the odour of the solvent is no longer perceptible.
Weigh the shell. The mass of the contents is the difference between the weighings. Repeat the procedure with another nineteen capsules.POWDERS FOR PARENTERAL USE: Remove any paper labels from a container and wash and dry the outside.
Open the container and without delay weigh the container and its contents.
Empty the container as completely as possible by gentle tapping, rinse it if necessary with water R and alcohol R and dry at 100 �C to 105 �C for 1 h, or, if the nature of the container precludes heating at this temperature, dry at a lower temperature to constant mass.
Allow to cool in a desiccator and weigh. The mass of the contents is the difference between the weighings. Repeat the procedure with another nineteen containers.
2.9.6. UNIFORMITY OF CONTENT OF SINGLE-DOSE PREPARATIONS
The test for uniformity of content of single-dose preparations is based on the assay of the individual contents of active ingredient of a number of single-dose units to determine whether the individual contents are within limits set with reference to the average content of the sample.
The test is not required for multivitamin and trace-element preparations and in other justified and authorised circumstances.
Method. Using a suitable analytical method, determine the individual contents of active ingredient of ten dosage units taken at random.
Apply the criteria of test A, test B or test C as specified in the monograph for the dosage form in question.TEST A
Tablets, powders for parenteral use, suspensions for injection. The preparation complies with the test if each individual content is between 85 per cent and 115 per cent of the average content. The preparation fails to comply with the test if more than one individual content is outside these limits or if one individual content is outside the limits of 75 per cent to 125 per cent of the average content.
If one individual content is outside the limits of 85 per cent to 115 per cent but within the limits of 75 per cent to 125 per cent, determine the individual contents of another twenty dosage units taken at random. The preparation complies with the test if not more than one of the individual contents of the thirty units is outside 85 per cent to 115 per cent of the average content and none is outside the limits of 75 per cent to 125 per cent of the average content.TEST B
Capsules, powders other than for parenteral use, granules, suppositories, pessaries. The preparation complies with the test if not more than one individual content is outside the limits of 85 per cent to 115 per cent of the average content and none is outside the limits of 75 per cent to 125 per cent of the average content. The preparation fails to comply with the test if more than three individual contents are outside the limits 85 per cent to 115 per cent of the average content or if one or more individual contents are outside the limits of 75 per cent to 125 per cent of the average content.
If two or three individual contents are outside the limits of 85 per cent to 115 per cent but within the limits of 75 per cent to 125 per cent, determine the individual contents of another twenty dosage units taken at random. The preparation complies with the test if not more than three individual contents of the thirty units are outside the limits of 85 per cent to 115 per cent of the average content and none is outside the limits of 75 per cent to 125 per cent of the average content.TEST C
Transdermal patches. The preparation complies with the test if the average content of the ten dosage units is between 90 per cent and 110 per cent of the labelled content and if the individual content of each dosage unit is between 75 per cent and 125 per cent of the average content.
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, capsules with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions. The test is not required for multivitamin and trace-element prep arations.
Uniformity of mass (2.9.5). Capsules comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
CHEWING GUMS, MEDICATED (1998:1239)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, medicated chewing gums with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test A for uniformity of content of single-dose preparations. If the preparation contains more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions.
Uniformity of mass (2.9.5). Uncoated medicated chewing gums and, unless otherwise justified and authorised, coated medicated chewing gums comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
EYE PREPARATIONS - Opthalmic inserts (1997:1163)
TESTS
Uniformity of content (2.9.6). Ophthalmic inserts comply, where applicable, with test A for uniformity of content.
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, single-dose granules with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test B for uniformity of content of single-dose preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Single-dose granules except for coated granules comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
INTRARUMINAL DEVICES (1998:1228)
TEST
Uniformity of content (2.9.6). Unless otherwise justified and authorised, constituent tablet units of intraruminal devices in which the active ingredients are present at levels less than 2 mg or less than 2 per cent of the total mass comply with test A for uniformity of content of single-dose preparations. If the preparation contains more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions.
Uniformity of mass (2.9.5). Unless otherwise justified and authorised, the constituent tablet units of intraruminal devices comply with the test for uniformity of mass.
If the test for uniformity of content is prescribed for all active ingredients, the test for uniformity of mass is not required.
LIQUIDS FOR ORAL USE (1997:0672)
TESTS
Uniformity of content. Unless otherwise prescribed or justified and authorised, single-dose liquids that are suspensions comply with the following test. After shaking, 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 of single-dose Preparations (2.9.6).
Uniformity of mass. Single-dose liquids that are solutions or emulsions comply with the following test: weigh individually the contents of twenty containers, emptied as completely as possible, and determine the average mass. Not more than two of the individual masses deviate by more than 10 per cent from the average mass and none deviates by more than 20 per cent.
Dose and uniformity of dose of oral drops. Into a suitable, graduated cylinder, introduce by means of the dropping device the number of drops usually prescribed for one dose or introduce by means of the measuring device, the usually prescribed quantity. The dropping speed does not exceed two drops per second. Weigh the liquid, repeat the addition, weigh again and carry on repeating the addition and weighing until a total of ten masses are obtained. No single mass deviates by more than 10 per cent from the average mass. The total of ten masses does not differ by more than 15 per cent from the nominal mass of ten doses. If necessary, measure the total volume of ten doses. The volume does not differ by more than 15 per cent from the nominal volume of ten doses.
LIQUID FOR ORAL USE - Powders and granules for oral solutions and suspensions (1997:0672)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, single-dose powders and single-dose granules with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with the test B for Uniformity of Content of Single-dose Preparations (2.9.6). If the preparation has more than one active ingredient, the requirement applies only to those ingredients that correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Single-dose powders and single-dose granules comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
NASAL PREPARATIONS - Nasal drops and liquid nasal sprays (1997:0676)
TESTS
Uniformity of mass. Nasal drops that are solutions comply with the following test: Weigh individually the contents of ten containers emptied as completely as possible, and determine the average mass. Not more than two of the individual masses deviate by more than 10 per cent from the average mass and none deviates by more than 20 per cent.
Metered dose nasal sprays that are solutions comply with the following test: Discharge once to waste. Wait for not less than 5 seconds and discharge again to waste. Repeat this procedure for a further three actuations. Weigh the mass of the container, discharge once to waste and weigh the remaining mass of the container. Calculate the difference between the two masses. Repeat the procedure for a further nine containers. They comply with the test if not more than two of the individual values deviate by more than 25 per cent from the average value and none deviates by more than 35 per cent.
Uniformity of content. 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 content. They comply with test B of uniformity of content (2.9.6).
Uniformity of delivered dose. 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 a container for 5 seconds and discharge once to waste. Wait for not less than 5 seconds, shake for 5 seconds and discharge again to waste. Repeat this procedure for a further three actuations. After 2 seconds, fire one 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 ingredient in the combined rinses.
Repeat the procedure for a further nine containers.
Unless otherwise justified and authorised, the preparation complies with the test if not more than one of the individual contents is outside the limits of 75 per cent to 125 per cent and none is outside the limits of 65 per cent and 135 per cent of the average content.
If two or three 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 twenty more containers. The preparation complies with the test if not more than three individual contents of the thirty individual contents are outside the limits of 75 per cent to 125 per cent and none is outside the limits of 65 per cent to 135 per cent of the average content.
PARENTERAL PREPARATIONS - Injections (1997:0520)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, single-dose suspensions for injection with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test A for uniformity of content of single-dose preparations. If the prep aration has more than one active ingredient, the requirement applies only to those ingredients that correspond to the above conditions.
The test is not required for multivitamin and trace-element preparations.
PARENTERAL PREPARATIONS - Powders for injections (1997:0520)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, powders for injections or intravenous infusions with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass or with a unit mass equal to or less than 40 mg comply with test A for uniformity of content of single-dose preparations. If the prep aration has more than one active ingredient, the requirement applies only to those ingredients that correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Powders for injections or intravenous infusions comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, single-dose oral powders with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test B for Uniformity of Content of Single-dose Preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Single-dose oral powders comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, single-dose topical powders with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test B for Uniformity of Content of single-dose Preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Single-dose topical powders comply with the test for uniformity of mass of single-dose prep arations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
RECTAL PREPARATIONS (1999:1145)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, solid single-dose preparations with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test A (tablets) or test B (suppositories, rectal capsules) for uniformity of content of single-dose preparations. If the preparation contains more than one active ingredient, this requirement applies only to those ingredients that correspond to the above conditions.
Uniformity of mass (2.9.5). Solid, single-dose preparations comply with the test for uniformity of mass. If the test for uniformity of content is prescribed for all active ingredients, the test for uniformity of mass is not required.
RECTAL PREPARATIONS - Rectal solutions and suspensions (1999:1145)
TEST
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, rectal suspensions 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.
Uniformity of mass. Rectal solutions comply with the following test: weigh individually the contents of twenty containers emptied as completely as possible, and determine the average mass. For containers the contents of which weigh not more than 100 g, not more than two of the individual masses deviate by more than 10 per cent from the average mass and none deviates by more than 20 per cent. For containers the contents of which weigh more than 100 g, not more than two of the individual masses deviate by more than 5 per cent from the average mass and none deviates by more than 10 per cent.
PRODUCTION
In the manufacture of sticks means are taken to ensure that the preparation complies with a test for mass uniformity or, where appropriate, a test for uniformity of content.
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, tablets with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test A for uniformity of content of single-dose preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions. The test is not required for multivitamin and trace-element preparations.
Uniformity of mass (2.9.5). Uncoated tablets and, unless otherwise justified and authorised, film-coated tablets comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
TRANSDERMAL PATCHES (1997:1011)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, transdermal patches comply with test C for uniformity of content of single-dose preparations.
VAGINAL PREPARATIONS (1997:1164)
TESTS
Uniformity of content (2.9.6). Unless otherwise prescribed or justified and authorised, solid single-dose preparations with a content of active ingredient less than 2 mg or less than 2 per cent of the total mass comply with test A (vaginal tablets) or test B (moulded pessaries, vaginal capsules) for uniformity of content of single-dose preparations. If the preparation has more than one active ingredient, the requirement applies only to those ingredients which correspond to the above conditions.
Uniformity of mass (2.9.5). Solid single-dose preparations comply with the test for uniformity of mass of single-dose preparations. If the test for uniformity of content is prescribed for all the active ingredients, the test for uniformity of mass is not required.
PREPARATIONS FOR INHALATION - Liquid preparations for inhalation (1999:0671)
PRODUCTIONPREPARATIONS FOR INHALATION - Powders for inhalation (1999:0671)
During the development of a preparation for inhalation which contains an antimicrobial preservative, the effectiveness of the chosen preservative shall be demonstrated to the satisfaction of the competent authority. A suitable method of test together with the criteria for judging the preservative properties of the formulation are described in the text on Efficacy of antimicrobial preservation (5.1.3).
The size of aerosol particles to be inhaled is controlled so that a significant fraction is deposited in the lung. The fine-particle characteristics of preparations for inhalation are determined by the method for Aerodynamic assessment of fine particles (2.9.18).
In assessing the uniformity of delivered dose, manufacturers may substitute alternative procedures, embracing more than one inhaler. Such procedures should assure conformity of all inhalers to the requirements of the Pharmacopoeia.
Pressurised metered-dose inhalers are tested for leakage. Inhalers are tested for extraneous particulate contamination.
TESTS
Uniformity of delivered dose. Containers usually operate in an inverted position. For containers that operate in an upright position, an equivalent test is applied using methods that ensure the complete collection of the delivered dose. In all cases, prepare the inhaler as directed in the instructions to the patient.
The dose collection apparatus must be capable of quantitatively capturing the delivered dose. The following apparatus and procedure may be used:
Figure 671.-1. - Dose collection apparatus for pressurised metered-dose preparations
Dimensions in millimeters
The apparatus (see Figure 671.-1) consists of a filter-support base with an open-mesh filter-support, such as a stainless steel screen, a collection tube that is clamped or screwed to the filter-support base, and a mouthpiece adapter to ensure an airtight seal between the collection tube and the mouthpiece. Use a mouthpiece adapter which ensures that the front face of the inhaler mouthpiece is flush with the front face of the sample collection tube. The vacuum connector is connected to a system comprising a vacuum source and a flow regulator. The source should be adjusted to pull air through the complete assembly, including the filter and the inhaler to be tested, at 28.3 � 1.5 litres per minute. Air should be drawn continuously through the apparatus to avoid loss of the active ingredient into the atmosphere. The filter support base is designed to accommodate 25 mm diameter filter disks. The filter disk and other materials used in the construction of the apparatus must be compatible with the active ingredient and solvents that are used to extract the active ingredient from the filter. One end of the collection tube is designed to hold the filter disk tightly against the filter-support base. When assembled, the joints between the components of the apparatus are airtight so that when a vacuum is applied to the base of the filter, all of the air drawn through the collection tube passes through the inhaler.
Unless otherwise prescribed in the instructions to the patient, shake the inhaler for 5 s and discharge one delivery to waste. Fire the inverted inhaler into the apparatus, depressing the valve for a sufficient time to ensure complete discharge. Repeat the procedure until the number of deliveries that constitute the minimum recommended dose have been sampled. Quantitatively collect the contents of the apparatus and determine the amount of active ingredient.
Repeat the procedure for a further two doses.
Discharge the device to waste, waiting not less than 5 s between actuations until n/2+1 deliveries remain, where n is the number of deliveries stated on the label. Collect four doses using the procedure described above.
Discharge the device to waste, waiting not less than 5 s between actuations until three doses remain. Collect these three doses using the procedure described above.
For preparations containing more than one active ingredient, carry out the test for uniformity of delivered dose for each active ingredient.
Unless otherwise justified and authorised, the preparation complies with the test if nine out of ten results lie between 75 per cent and 125 per cent of the average value and all lie between 65 per cent and 135 per cent. If two or three values lie outside the range of 75 per cent to 125 per cent, repeat the test for two more inhalers. Not more than three of the thirty values lie outside the range 75 per cent to 125 per cent and no value lies outside the range 65 per cent to 135 per cent.
Fine particle dose. Using an apparatus and procedure described in Aerodynamic assessment of fine particles(2.9.18), calculate the fine particle dose.
Number of deliveries per inhaler. Take one inhaler and discharge the contents to waste, actuating the valve at intervals of not less than 5 s. The total number of deliveries so discharged from the inhaler is not less than the number stated on the label. (This test may be combined with the test for uniformity of delivered dose).
Uniformity of delivered dose. In all cases, prepare the inhaler as directed in the instructions to the patient. The dose collection apparatus must be capable of quantitatively capturing the delivered dose. A dose collection apparatus similar to that described for the evaluation of pressurised metered-dose inhalers may be used provided that the dimensions of the tube and the filter can accommodate the measured flow rate. A suitable tube is defined in Figure 671.-1.CYANOCOBALAMIN (57CO) CAPSULES (1997:0710)
Connect the tube to a flow system according to the scheme specified in Figure 671.-2 and Table 671.-1.
Table 671.-1. - Component Specification for Figure 671.-2.
Code
Item
Description
A
Sample collection tube
Capable of quantitatively capturing the delivered dose, e.g. Dose collection tube similar to that described in Fig. 67-1 with dimensions of 34.85 mm ID x 12 cm length (e.g. product number XX40 (047 00, Millipore Corporation, Bedford, MA 01732 with modified exit tube, ID ³ 8 mm, fitted with Gelman product numer 61631), or equivalent.
B
Filter
47 mm filter, e.g. A/E glass fibre filter (Gelman Sciense, Ann Arbor, MI 48106), or equivalent
C
Connector
ID ³ 8 mm, e.g. short metal coupling, with low diameter branch to P3.
D
Vacuum tubing
8 ± 0.5 mm ID x 50 ± 10 cm length, e.g., silicone tubing with an OD of 14 mm and an ID of 8 mm.
E
Two-way solenoid valve
Minimum airflow resistance orifice having an ID of ³ 8 mm and a maximum responce time of 100 ms ( e.g. type 256-A08, Bürker GmbH, D7118), or equivalent.
F
Vacuum pump
Pump must be capable of drawing the required air flow rate through the assembled apparatus with the dry powder inhaler in the mouth piece adapter (e.g. product type 1023, 1423 or 2565, Gast manufacturing Inc., Benton harbor. M1 49022), or equivalent. Connect the pump to the solenoid valve using short and/or wide (³ 10 mm ID) vacuum tubing and connectors to minimise pump requirements.
G
Timer
Timer capable of driving the solenoid valve for the required time period (e.g. type G814, RS Components International, Corby, NN17 9RS, UK), or equivalent
P1
pressure tap
2.2 mm ID, 3.1 mm OD, flush with internal surface of the sample collection tube, centred and burr- free, 59 mm from its inlet.
P1,P2, P3
pressure measurements
Differential pressure to atmosphere (P1) or absolute pressure (P2 and P3).
H
Flow control valve
Adjustable regulating valve with maximum Cv ³ 1, (e.g. type 8FV12LNSS, Parker Hannifin plc., Barnstaple, EX31 1NP, UK), or equivalent.
Figure 671.-2. - Apparatus suitable for measuring the uniformity of delivered dose for powder inhalers
Unless otherwise defined, determine the test flow rate and duration using the dose collection tube, the associated flow system, a suitable differential pressure meter and a suitable volumetric flow meter, calibrated for the flow leaving the meter, according to the following procedure:
Prepare the inhaler for use and connect it to the inlet of the apparatus using a mouthpiece adapter to ensure an airtight seal. Use a mouthpiece adapter which ensures that the front face of the inhaler mouthpiece is flush with the front face of the sample collection tube. Connect one port of a differential pressure meter to the pressure reading point, P1, in Figure 671.-2 and let the other be open to the atmosphere. Switch on the pump, open the two way valve and adjust the flow control valve until the pressure drop across the inhaler is 4.0 kPa (40.8 cm H2O) as indicated by the differential pressure meter. Remove the inhaler from the mouthpiece adapter and without touching the flow control valve, connect a flow meter to the inlet of the sampling apparatus. If the flow rate is above 100 litres per minute adjust the flow control valve to obtain a flow rate of 100 � 5 litres per minute. Note the volumetric airflow rate and define this as the test flow rate, Q, in litres per minute. Define the test flow duration, T, in seconds so that a volume of 4 litres of air is drawn through the inhaler.
Ensure that critical flow occurs in the flow control valve by the following procedure. With the inhaler in place and the test flow rate Q, measure the absolute pressure on both sides of the control valve (pressure reading points P2 and P3 in Figure 671.-2). A ratio P3/P2 = 0.5 indicates critical flow. Switch to a more powerful pump and re-measure the test flow rate if critical flow is not indicated.
Pre-metered systems. Prepare the inhaler as directed in the instructions to the patient and connect it to the apparatus using an adapter which ensures a good seal. Draw air through the inhaler using the predetermined conditions. Repeat the procedure until the number of deliveries which constitute the minimum recommended dose have been sampled. Quantitatively collect the contents of the apparatus and determine the amount of active ingredient.
Repeat the procedure for a further nine doses.
Reservoir systems. Prepare the inhaler as directed in the instructions to the patient and connect it to the apparatus using an adapter which ensures a good seal. Draw air through the inhaler under the predetermined conditions. Repeat the procedure until the number of deliveries which constitute the minimum recommended dose have been sampled. Quantitatively collect the contents of the apparatus and determine the amount of active ingredient.
Repeat the procedure for a further two doses.
Discharge the device to waste until n/2+1 deliveries remain, where n is the number of deliveries stated on the label. If necessary, store the inhaler to discharge electrostatic charges. Collect four doses using the procedure described above.
Discharge the device to waste until three doses remain. If necessary, store the inhaler to discharge electrostatic charges. Collect three doses using the procedure described above.
For preparations containing more than one active ingredient, carry out the test for uniformity of delivered dose for each active ingredient.
The preparation complies with the test if nine out of ten results lie between 75 per cent and 125 per cent of the average value and all lie between 65 per cent and 135 per cent. If two or three values lie outside the range of 75 per cent to 125 per cent, repeat the test for two more inhalers. Not more than three of the thirty values lie outside the range 75 per cent to 125 per cent and no value lies outside the range 65 per cent to 135 per cent.
In justified and authorised cases, these ranges may be extended but no value should be greater than 150 per cent or less than 50 per cent of the average value.
Uniformity of content. Determine by measurement in a suitable counting assembly and under identical geometrical conditions the radioactivity of each of not less than ten capsules. Calculate the average radioactivity per capsule. The radioactivity of no capsule differs by more than 10 per cent from the average. The relative standard deviation is less than 3.5 per cent.SODIUM IODIDE (131I) CAPSULES FOR DIAGNOSTIC USE (1997:0938)
Uniformity of content. Determine by measuring in a suitable counting assembly and under identical geometrical conditions, the radioactivity of each of not less than ten capsules. Calculate the average radioactivity per capsule. The radioactivity of no capsule differs by more than 10 per cent from the average. The relative standard deviation is not greater than 3.5 per cent.HOMOEOPATHIC PREPARATION (1999:1038)
Dosage forms
A dosage form of a homoeopathic preparation complies with any relevant dosage form monograph in the European Pharmacopoeia and with the following:
- for the purpose of dosage forms for homoeopathic use "active ingredients" are considered to be "dilutions or triturations of homoeopathic stocks",
- these dosage forms are prepared using appropriate excipients,
- the test for uniformity of content is normally not appropriate. However, in certain circumstances, it is required.
