Establishing acceptance limits for uniformity of dosage units

Pramote Cholayudth

Biolab and PM Consult,Samutprakarn 10540,Thailand

Establishing acceptance limits for uniformity of dosage units

Pramote Cholayudth*

Biolab and PM Consult,Samutprakarn 10540,Thailand

A R T I C L E I N F O

Article history:

Available online 23 November 2015

Uniformity of dosage units

Acceptance value

Acceptance limit

Acceptance value(AV)distribution

Uniformity of dosage units[1]is one of the most commonly employed compendial tests to evaluate the dosage units.In the test,the acceptance value(AV)is the key statistics-based acceptance parameter with the limit of not more than 15 to measure the uniformity degree of the dosage units in terms of content uniformity or weight variation as applicable.With quality assurance(QA)principle,there should be some kinds of predetermined acceptance limits,like Bergum method introduced by James S.Bergum in 1990[2]and 2007 [3]and recently recognized by ASTM 2709[4]and ASTM 2810 [5]to ensure that the AV results for any future quality control(QC)samples will not exceed the compendial limit (NMT 15).

Since AV is a kind of sample statistics,sampling distribution of the AV data can be plotted as AV distribution(Fig.1). To develop the AV probability density function(pdf)formula is to derive from McKay’s coeffcient of variation(CV)distribution equation[6].To confrm the validity of the formula is to conduct a computer simulation using MS Excel program. Fig.1 also illustrates the successful simulation test result.One of the key benefts of the constructed AV distribution is to establish the predetermined acceptance limit for AV results,say the percentage point at 99%of the distribution(i.e.AV NMT 12),rather than directly using the compendial limit.For validation data(samples greater than QC samples),validation acceptance criteria can be established as well.

Fig.1–Acceptance Value(AV)Distribution.

R E F E R E N C E S

[1]The United States Pharmacopeial Convention,Inc.<905> Uniformity of dosage units.37th ed.United States Pharmacopeia;2014.

[2]Bergum JS.Constructing acceptance limits for multiple stage tests.Drug Dev Ind Pharm Marcel Dekker,Inc.1990;16:2153–2166.

[3]Bergum JS,Li H.Acceptance limits for the new ICH USP 29 content-uniformity test.Pharm Technol 2007;31(10).

[4]ASTM Standard.#E 2709–09:standard practice for demonstrating capability to comply with a lot acceptanceprocedure,September 2009.

[5]ASTM Standard.#E2810–11:standard practice for demonstrating capability to comply with the test for uniformity of dosage units,October 2011.

[6]McKay A.Distribution of the coeffcient of variation and the extended‘T’distribution.J R Stat Soc 1932;95:695–698.

*E-mail address:cpramote2000@yahoo.com.

Peer review under responsibility of Shenyang Pharmaceutical University.

http://dx.doi.org/10.1016/j.ajps.2015.10.027

1818-0876/©2016 Production and hosting by Elsevier B.V.on behalf of Shenyang Pharmaceutical University.This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).