Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition.
Optimisation of Pharmaceutical Cocrystal Dissolution Performance through a Synergistic Precipitation Inhibition.
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DOI：
10.1007/s11095-023-03532-x
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发表时间：
2023-08
影响因子：
3.7
通讯作者：
Li, Mingzhong
中科院分区：
文献类型：
--
作者：
Shi, Kejing;Li, Mingzhong
聚合物赋形剂在共晶制剂中发挥重要作用，作为沉淀抑制剂，以最大限度地发挥潜力。否则，在共晶溶解过程中，母体药物的稳定形式将在溶解的共晶表面上和/或本体溶液中重结晶，从而抵消溶解度优势。这项工作的目的是调查使用组合聚合物的潜力，以最大限度地提高表面沉淀药物共晶的溶出性能。已经系统地研究了高度可溶的氟芬那酸和烟酰胺（FFA-NIC）共晶体的溶解性能，其中预溶解或粉末与单一聚合物混合，包括表面沉淀抑制剂[即，乙烯基吡咯烷酮（60%）/乙酸乙烯酯（40%）的共聚物（PVP-VA）]和两种本体沉淀抑制剂[即，聚乙二醇（PEG）和Soluplus（SLP）]或二元聚合物组合。PVP-VA的单一聚合物防止FFA表面沉淀，从而增强FFA-NIC共晶的溶解性能。不幸的是，它不能维持本体溶液中的过饱和FFA浓度。PVP-VA和SLP两种聚合物的组合显示出协同抑制作用，以增强FFA-NIC共晶的溶解优势。具有母体药物表面沉淀的共晶的溶解可描述为：i）共晶表面接触溶解介质; ii）共晶表面溶解; iii）母体药物沉淀在溶解表面上;和iv）母体药物颗粒再溶解。两种类型的聚合物的组合可用于使溶液中的共晶性能最大化。在线版本包含补充材料，可通过10.1007/s11095-023-03532-x获得。
Polymeric excipients play an important role in a cocrystal formulation to act as precipitation inhibitors to maximize the potential. Otherwise, a stable form of the parent drug will be recrystallized on the dissolving cocrystal surface and/or in the bulk solution during the cocrystal dissolution process, negating the solubility advantage. The objectives of this work were to investigate the potential of using combined polymers to maximise the dissolution performance of surface precipitation pharmaceutical cocrystals. The dissolution performance of a highly soluble flufenamic acid and nicotinamide (FFA-NIC) cocrystal has been systematically studied with predissolved or powder mixed with a single polymer, including a surface precipitation inhibitor [i.e., copolymer of vinylpyrrolidone (60%) /vinyl acetate (40%) (PVP-VA)] and two bulk precipitation inhibitors [i.e., polyethylene glycol (PEG) and Soluplus (SLP)], or binary polymers combinations. A single polymer of PVP-VA prevented the FFA surface precipitation for an enhanced dissolution performance of FFA-NIC cocrystal. Unfortunately, it cannot sustain the supersaturated FFA concentration in the bulk solution. A combination of two polymers of PVP-VA and SLP has shown a synergistic inhibition effect to enhance the dissolution advantage of FFA-NIC cocrystal. The dissolution of a cocrystal with surface precipitation of the parent drug can be described as: i) the cocrystal surface contacting the dissolution medium; ii) the cocrystal surface dissolving; iii) the parent drug precipitation on the dissolving surface; and iv) the parent drug particles redissolving. A combination of two types of polymers can be used to maximise the cocrystal performance in solution. The online version contains supplementary material available at 10.1007/s11095-023-03532-x.
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