Recent advances in improving oral drug bioavailability by cocrystals.
Recent advances in improving oral drug bioavailability by cocrystals.
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DOI：
10.15171/bi.2018.33
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Barzegar-Jalali M
中科院分区：
文献类型：
--
作者：
Emami S;Siahi-Shadbad M;Adibkia K;Barzegar-Jalali M
引言：口服给药是最受欢迎的给药途径。然而，口服生物利用度差是临床疗效不足的主要原因之一。改善具有低水溶性和/或低肠膜渗透性的药物的口服吸收是一个活跃的研究领域。药物与适当的共形成物共包合是提高口服生物利用度的一种有前途的方法。 方法：在本综述中，我们重点介绍了通过共结晶改善口服吸收的最新进展。所涵盖的领域包括过饱和度及其对共晶体口服吸收的重要性，共晶体通过膜的渗透性，药物-共形成剂药代动力学（PK）相互作用，共晶体的体内-体外相关性。此外，还讨论了超分子设计与分子组装技术的结合。还报告了市售共晶产品和人类受试者的PK研究。 结果如下：在评价共晶的溶出度和生物利用度时，必须考虑过饱和度和随后的沉淀特性。应包括适当的赋形剂以控制沉淀动力学和捕获共晶的溶解度优势。除了溶解度外，共晶还可以改变药物的膜渗透性。因此，共晶可用于改善渗透性差的药物的口服生物利用度。已经表明，共晶可能会破坏细胞单层的细胞完整性，这可能会引起毒性问题。某些共构体可能通过改变肠道血流量、代谢和抑制外排泵等途径影响药物在肠道的吸收。因此，在进行生物利用度研究时应谨慎。纳米尺寸的共晶体已经显示出改善难溶性药物吸收的高潜力。 结论：共晶体已经从原理验证阶段走向临床。到目前为止，至少有两种共晶产品获得了监管机构的批准。然而，在安全性、预测体内行为和揭示共晶体在人体中的真实的潜力方面仍存在挑战。
Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human.
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影响因子：
4.9
作者：
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通讯作者：
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