質量均一性：以打錠操作壓縮條件對於有刻痕錠劑分割之影響作為製造時耐變性評估之一部份   全文下載

Mass Uniformity: Influence of Operational Compression Conditions on Breakability of Scored Tablets as Part of Manufacturing Robustness Evaluation

劑量均一性是藥品品質的關鍵要素之一。本研究之目的是證明以一個實用的評估錠劑分割之耐變性的方法，可作為有刻痕錠劑打錠確效之一部分。本研究係採用相同處方不同大小兩種形態之十字刻痕圓形錠，以探討打錠操作時之壓縮因子（速度及壓力）對於二分之ㄧ錠與四分之ㄧ錠之重量差異的影響。由實驗結果顯示，本試驗採用之動物用藥錠劑在打錠製造時，改變上述兩種壓縮因子（速度及壓力），對於錠劑由分線分割後稱重之重量差異性，並不具有有意義之影響。經驗法則以及本調查均可確認，由不同劑量比率錠劑分線分割後稱重，所得之標準差與原來錠劑之重量成線性關係。二分之ㄧ錠與四分之ㄧ錠之重量差異間，存在有密切的相關性：作者以前所提之純理論模式於本文再被證實，證明經由分割導致外加之變異與錠劑上刻痕長度呈線性函數。本研究結果顯示，十字刻痕圓形錠分線分割後稱重之二分之ㄧ錠及四分之ㄧ錠，其標準差以質量單位表示，將維持大致相同。然而，當二分之ㄧ錠劑由分線分割成四分之ㄧ錠劑時，四分之ㄧ錠劑重量之相對標準差，為由錠劑分線分割成二分之ㄧ錠劑之相對標準差之2倍。

Dose uniformity is a key quality element of drugs. The purpose of this study was to demonstrate a practical approach to evaluate the breakability robustness as part of the tabletting validation of a scored tablet. The influence of operational compression parameters (speed and force) on the weight variabilities of half- and quarter-tablets was investigated using two types of cross-scored round tablets of identical composition but different in size. It was shown for the used veterinary model tablet that manufacturing variation of two compression parameters around the defined target values do not significantly influence the weight variability of the broken tablets. The empirical guidance was also confirmed that for the investigated dose-proportional tablets the standard deviation of the broken tabletpart weight is linearly related to the original tablet weight. There exists a strong correlation between the variability of half-tablets and of quarter-tablets: the theoretical model previously presented was refined, demonstrating that the additional variance induced by breaking is a linear function of the break-line length. As a consequence, the standard deviation of half- and quarter-parts of crossscored round tablets, expressed in mass units, will thus remain approximately identical. Hence, the relative standard deviation (RSD) of quarter-tablet weights will nearly double when breaking half-tablets into quarter-tablets.