背景:口服给药途径是最广泛和首选的给药途径,但它有几个限制,包括可变药代动力学(PK),减少溶解和吸收,和胃肠道刺激。Further,许多化合物的水溶性低,这也限制了肠道的吸收。
方法:对于这篇叙述性综述,我们对PubMed进行了文献检索,直到2022年8月,重点是乳液,微乳液,纳米乳液,和自乳化药物递送系统。
结果:自微乳化药物递送系统(SMEDDS)克服了疏水性化合物的这些限制,以提高其生物利用度。一个SMEDDS配方是一个明确的,热力学稳定,脂质的水包油乳液,溶解的药物,和两种表面活性剂,自发形成直径<100nm的液滴。这些成分有助于将预先溶解的药物输送到胃肠道,同时保护它们免受胃酸或首过肝代谢的降解。SMEDDS制剂在治疗癌症(紫杉醇)中改善了口服药物递送,病毒感染(利托那韦),和偏头痛(布洛芬和塞来昔布口服液)。美国头痛协会最近更新了他们关于偏头痛急性治疗的共识声明,并包括一种在SMEDDS中配制的选择性环加氧酶-2选择性抑制剂,塞来昔布口服液.与塞来昔布胶囊相比,这种SMEDDS制剂显示出生物利用度的显着改善,允许在口服溶液中使用低剂量的塞来昔布,以提供安全有效的急性偏头痛治疗。这里,我们将专注于SMEDDS配方,它们与其他类似乳液作为难溶性药物的载体有什么区别,及其在偏头痛急性治疗中的临床应用。
结论:在SMEDDS中重新配制的口服药物显示出达到血浆药物浓度峰值的时间加快,最大血浆浓度增加,与胶囊相比,片剂,或暂停。SMEDDS技术提高了亲脂性药物的药物吸收和生物利用度,与其他配方相比。临床上,这允许使用具有改善的PK曲线的较低剂量,而不影响功效,如所示用塞来昔布口服液治疗急性偏头痛。
BACKGROUND: The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption.
METHODS: For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems.
RESULTS: The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100 nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine.
CONCLUSIONS: Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.