Co-crystallization of hemp oil constituents and assessment for bioaccessibility using the TIM-1 in vitro gastrointestinal digestion model

在加拿大，大麻可能会被开成医生推荐的草药疗法。虽然大麻通常是吸烟的，但吸入燃烧的干燥植物物质有明显的固有健康风险。口服给药有几个关键的好处，包括消除肺部健康风险和更准确地给药有效成分，如THC和CBD。然而，口服给药也面临着一定的缺陷和挑战。生物利用度被定义为一种药物或其他物质在进入体内时进入循环并因此能够产生积极作用的比例。因此，在开发用于口服的大麻制剂时，这是一个需要评估的重要特性。到目前为止，研究表明，广泛的肝脏代谢将THC的口服生物利用度降低到大约2-14%，而吸入大麻烟雾提供的全身生物利用度通常在10%-35%之间。其他人报告口服后的生物利用度约为6%，而吸烟后的生物利用度为25%。我们目前研究项目的目标是开发新的大麻素制剂，以努力提高口服生物利用度。评估生物利用度带来了一些严重的挑战，因为需要人类或动物受试者，而且必须提取血浆样本。荷兰TNO公司开发的TIM-1体外胃肠消化模型是一种与体内试验高度相关的先进溶出模型，并已被用于药物释放试验。在处理人类或动物试验对象时，可以快速和经济有效的方式评估新配方的生物利用度，而不需要伦理批准。这将允许对配方进行快速评估，并大大提高创新和发现提高大麻素口服生物利用度的速度。

In Canada, cannabis may be prescribed as a physician-recommended herbal therapy. While cannabis is typicallysmoked, inhalation of burned dry plant matter has obvious inherent health risks. Oral administration offersseveral key advantages, including elimination of pulmonary health risks and more accurate dosing of activeingredients such as THC and CBD. Oral administration does, however, suffer certain shortcomings andchallenges as well. Bioavailability is defined as the proportion of a drug or other substance that enterscirculation when introduced into the body and so is able to have an active effect. This is therefore an importantproperty to assess when developing cannabis formulations for oral administration. Research has thus far shownthat extensive liver metabolism reduces the oral bioavailability of THC to roughly 2-14%, while inhalation ofmarijuana smoke offers a systemic bioavailability generally ranging between 10-35%. Others have reportedTHC bioavailability after oral ingestion to be approximately 6% compared to 25% after smoking. The goal ofour current research project is to develop novel formulations of cannabinoids in an effort to improve oralbioavailability. Assessing for bioavailability poses some serious challenges, as human or animal subjects arerequired and plasma samples must be drawn. The TIM-1 simulated in vitro gastrointestinal digestion modeldeveloped by TNO in the Netherlands is an advanced dissolution model with high correlation to in vivo testingand has been validated for use in drug delivery testing. Novel formulations can be assessed for bioavailabilityin a quick and cost-effective manner without the need for ethical approval when dealing with human or animaltest subjects. This will allow rapid assessments of formulations and significantly increase the rate of innovationand discovery into enhancing oral bioavailability of cannabinoids.