Dissolution profiles of high-dose salt-form drugs in bicarbonate buffer and phosphate buffer.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Yuki Tarumi, Kiyohiko Sugano
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引用次数: 0

Abstract

The purpose of the present study was to compare the dissolution profiles of high-dose salt-form drugs in bicarbonate buffer (BCB) and phosphate buffer (PPB) focusing on the pH changes in the bulk phase. The pH titration curves of BCB and PPB (pH 6.5, buffer capacity (β) = 4.4 mmol/L/pH unit) were first theoretically calculated and experimentally validated. For dissolution tests, six drug salts with an acid counterion, one drug salt with a weak base counterion, and one free acid drug were employed (125-800 mg clinical dose). The dose/fluid volume ratio (Dose/FV) was aligned with the clinical condition. In the pH titration study, the pH value decreased below pH 6.0 by adding HCl > 2.8 mmol/L (BCB) or > 1.6 mmol/L (PPB) and increased above pH 7.0 by adding NaOH > 2.0 mmol/L (BCB) or > 2.4 mmol/L (PPB). In the dissolution test, even though the initial pH and β values were the same, the pH value at 4 h was lower in PPB than in BCB in all cases. For the drug salts with an acid counterion, the area under the dissolution curve was 1.2 to 2.6-fold lower in BCB than in PPB. A marked precipitation process was observed in BCB, but less pronounced or absent in PPB. The results of this study suggest the use of BCB and a clinically equivalent Dose/FV may be valuable in predicting the oral absorption of high-dose drug salts.

高剂量盐形式药物在碳酸氢盐缓冲液和磷酸盐缓冲液中的溶解曲线。
本研究的目的是比较大剂量盐形式药物在碳酸氢盐缓冲液(BCB)和磷酸盐缓冲液(PPB)中的溶出曲线,重点关注体相中的 pH 值变化。首先对 BCB 和 PPB(pH 值为 6.5,缓冲能力 (β) = 4.4 mmol/L/pH 单位)的 pH 滴定曲线进行了理论计算和实验验证。溶解试验采用了六种含酸性反离子的药物盐、一种含弱碱反离子的药物盐和一种游离酸性药物(临床剂量为 125 至 800 毫克)。剂量/液体体积比(Dose/FV)与临床情况一致。在 pH 滴定研究中,加入 HCl > 2.8 mmol/L(BCB)或 > 1.6 mmol/L(PPB)时,pH 值下降至 pH 6.0 以下;加入 NaOH > 2.0 mmol/L(BCB)或 > 2.4 mmol/L(PPB)时,pH 值上升至 pH 7.0 以上。在溶解试验中,尽管初始 pH 值和 β 值相同,但在所有情况下,PPB 在 4 小时后的 pH 值均低于 BCB。对于含有酸性反离子的药物盐,BCB 的溶解曲线下面积比 PPB 低 1.2 至 2.6 倍。在 BCB 中观察到明显的沉淀过程,而在 PPB 中则不明显或没有沉淀。本研究结果表明,使用 BCB 和临床等效剂量/FV 可能对预测大剂量药物盐的口服吸收很有价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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