Size of discrete dosage forms
The tests specified in TGO 101, and in the various pharmacopoeia referenced by the Order, are designed to ensure that medicines are of appropriate quality and are therefore safe to use and can deliver the intended therapeutic benefit.
The size and shape of tablets, capsules and pills are not regulated by any requirements within TGO 101. However, these attributes can significantly affect the safety profile of the medicine if they present a choking hazard. Swallowing difficulties can also contribute to non compliance with treatment regimens.
The United States Food and Drug Administration (US FDA) document Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules - Guidance for Industry (pdf,89kb) includes recommendations about the size of tablets and capsules. This document recommends that largest dimension of a tablet or capsule should not exceed 22mm and that capsules should not exceed a standard 00 size. Sponsors should consider the size, shape, use of coating materials and the intended patient population to minimise the risk of the dosage units presenting a choking hazard.
Sponsors should be particularly mindful of choosing solid dosage forms, particularly soft gel capsules, for medicines intended for children under five years of age. These dosage forms may present a choking hazard as this population may not have a full set of teeth, be able to adequately chew, or be able to swallow, a whole dosage unit.
Uniformity of dosage units
Listed medicines are not required to comply with requirements for uniformity of dosage units.
Section 12 in Part 2 allows listed medicines to substitute a uniformity of dosage unit requirement in an applicable monograph with a test for uniformity of weight (mass).
Similarly, section 20 in Part 2 states that the requirement of uniformity for listed medicines is item 4 in the table in Schedule 1, i.e. uniformity of weight (mass). This requirement doesn't preclude a sponsor choosing to test for uniformity of dosage units for a listed medicine. Compliance with such a test would be considered as demonstrating compliance with uniformity of weight (mass).
Testing methods for pills
The following testing procedures are provided to assist sponsors in confirming compliance of pills with the Order. Alternative methods can be used but in the case of dispute, the TGA would rely on results generated using the stated methodology.
Methodology to be used for disintegration testing is included as a requirement in the Order.
Determination of water
Should be carried using an appropriate method such as oven drying, toluene distillation, drying under reduced pressure or gas chromatography.
Uniformity of weight
Dripping pills and sugar pills
Procedure - weigh accurately 20 pills and calculate the average weight, then weigh each of them accurately. Compare the weight of each pill with the labelled or average weight. Not more than two (2) pills should deviate from the limit of weight variation, and none should deviate from twice the limit.
Procedure - Take 10 pills as one part or, for pills weighing 1.5g or more, each pill is a part.
Weigh separately 10 parts and compare with the labelled weight of each part (labelled weight of each pill X the number of pills weighed). If there is no labelled weight, compare the weight of each pill with the average weight calculated. Not more than two (2) parts should deviate from twice the limit.
Procedure - Take ten packs (or vials) of pills, weigh separately the content of each pack (or vial) and compare with labelled weight.