Isoniazid, Pyrazinamide and Rifampicin Content Variation in Split Fixed-Dose Combination Tablets

<div><p>Setting</p><p>In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets.</p><p>Objective</p><p>To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis.</p><p>Design</p><p>Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets.</p><p>Results</p><p>All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings.</p><p>Conclusion</p><p>In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.</p></div

Summary of halves and thirds tablets content variation using the weight-adjustment correction.

<p><i>USP proxy defined as 85</i>–<i>115% of the expected content</i>.</p

Acceptance Values (AV) for the content uniformity according to the USP monograph 905 (for the three drugs in whole, half and third portions, the accepted limit was set up <15).

<p>Acceptance Values (AV) for the content uniformity according to the USP monograph 905 (for the three drugs in whole, half and third portions, the accepted limit was set up <15).</p

Labelled content variation in whole, half and third tablets.

<p>Results are presented as individual values and with mean and the 95% confidence interval of the mean for each drug and dataset. The dashed lines represent the 85–115% USP proxy.</p

Demographic characteristics and self-medication with antibiotics (SMA) in STU students (n = 1,300).

*<p>NaN, not a number.</p

Classified groups of students and self-medication with antibiotics (n = 1,300).

a<p>students from schools/colleges of Liberal Arts, Law, Business, Art and Design, and Journalism and Communication;</p>b<p>students from colleges of Science and Engineering;</p>c<p>1^st-year medical students;</p>d<p>all medical students except 1^st year students; PKA, prior knowledge of antibiotics;</p>e<p>students from all groups except PKA group;</p>f<p>p>0.05, science/non-medicine group vs. medicine/non-PKA group;</p>g<p>p<0.0001, PKA group vs. science/non-medicine group; p<0.0001, PKA group vs. medicine/non-PKA group.</p

Ten most commonly used antibiotics for self-medication in STU students (n = 508^*).

*<p>69 out of 621 self-medicated students failed to mention the names of antibiotics they used.</p