ABSTRACT
A representative market surveillance study on break-mark tablets for human use, having a marketing authorization (MA) in The Netherlands (NL), was carried out. The uniformity of mass of subdivided break-mark tablets into halves was assessed according to Ph.Eur.5.5, now current; and for comparison also according to Ph.Eur. 4.1 (no longer in force) and Pharmeuropa 16.2. The compliance was 24%, 14% and 45%, respectively. The compliance with a criterion for loss of mass by subdivision of break-mark tablets (< or = 1.0% of the total mass) was 86%. The compliance with a criterion for ease of subdivision of break-mark tablets (> or = 80% of a panel of elderly able to break, > or = 90% probability) was 34%. Of the 29 studied tablets, 5 complied with all criteria, amongst which were all three oblong tablets that were included in the study. The Summary of Product Characteristics (SmPC) of the tablets was independently evaluated by experts to assess whether their break-mark was needed for the posology. The experts came to a uniform conclusion for only 66% of the tablets. It is concluded that the proposed test procedures for ease of subdivision and loss of mass by subdivision are workable, that the proposed criteria are reasonable and that their inclusion in Ph.Eur. can be considered. From a pharmaceutical-technological point of view, the requirements of Ph.Eur. 5.5 Subdivision of tablets for uniformity of mass of subdivided tablets, and the proposed criteria for ease of subdivision and loss of mass, are all simultaneously attainable. It is also concluded that the majority of the break-mark tablets with a MA in NL do not meet the requirements of Ph.Eur.5.5 Subdivision of tablets, and that they do not fulfill the proposed criterion for ease of subdivision. This is expected to also be the case in other countries. It is proposed that the test Ph.Eur. 5.5 Subdivision of tablets should give instructions on how to handle tablets that cannot be broken, or that crumble upon subdivision. It is also proposed that the criteria Ph.Eur. 5.5 Subdivision of tablets should not be restricted to break-marks needed for the posology, as dosing instructions in SmPCs are open to different interpretations, and that this restriction should be deleted.
Subject(s)
Pharmacopoeias as Topic , Product Surveillance, Postmarketing , Tablets/standards , Technology, Pharmaceutical/standards , Adult , Chemistry, Pharmaceutical/standards , Guideline Adherence , Guidelines as Topic , Hardness , Humans , Middle Aged , Netherlands , Pressure , Quality Control , Technology, Pharmaceutical/methodsABSTRACT
An in vivo test for ease of breaking of scored tablets was developed. Scored tablets covering a wide range of dimensions, type of break-mark and ease of breaking were used as training set. Test panels of healthy volunteers (25-61 years old), and panels of elderly (mean age > or =75 years old) were used. Five different test procedures were investigated. Subjective assessment of ease of breaking appeared more cumbersome than objective scaling in "breakable" and "not breakable". Elderly were far less able to break the tablets than healthy volunteers. So, healthy volunteer panels are not a good substitute for the "worst case" patients situation. A test procedure is proposed specifying that not less than 80% of a panel of elderly (mean age > or =75 years old and none younger than 65 years old) must be able to break the scored tablet, with a confidence of not less than 90%.
