Grimling Bożena, Fast Magdalena, Okoniewska Magdalena, Owczarek Artur, Karolewicz Bożena
Department of Drug Form Technology, Wroclaw Medical University, Borowska 211 A, 50-556 Wroclaw, Poland.
Pharmaceutical Company Okoniewscy "Vetos-Farma" Sp. z o.o., ul. Dzierżoniowska 21, 58-260 Bielawa, Poland.
Pharmaceuticals (Basel). 2025 Jan 9;18(1):73. doi: 10.3390/ph18010073.
The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain. In this study, two substrates from suppositories with standardized (CEX) were used: cocoa butter and Witepsol H15.
The long-term stability of CEX was investigated over a period of up to 24 months. The concentrations of ∆-9-THC, cannabidiol (CBD), and cannabinol (CBN) were determined using an HPLC method. Furthermore, the water content of the extract, the ethanol residue, and the microbiological purity were determined. The pharmaceutical properties of CEX-incorporated suppositories, namely content uniformity, hardness, softening time, total deformation time, disintegration time, and the release profile of ∆-9-THC, CBD, and CBN, were evaluated in order to develop optimal preparation procedures for pharmacists.
Following a 24-month stability study on CEX, no significant alterations in component content were observed beyond the specified requirements. The disintegration time, total deformation time, and hardness of the suppositories based on Witepsol H15 with CEX were found to be longer and higher, respectively, than those of suppositories formulated with cocoa butter. In vitro studies demonstrated that suppositories prepared with Witepsol H15 exhibited superior release of ∆-9-THC compared to those prepared with cocoa butter.
We suggest that pharmacists making prescription drugs in a pharmacy setting in the form of medical marijuana suppositories will receive a better release profile of the drug by choosing Witepsol® H15 as a substrate.
药用大麻原料的正式实施允许医生开处方，药剂师制备基于大麻的制剂。药物研发和制造工艺优化工作的目标是提出一种含有25毫克和50毫克四氢大麻酚（∆-9-THC）剂量的栓剂配方，作为现有吸入或口服制剂的替代方案。该配方可用于直肠或阴道给药，从而在治疗子宫内膜异位症和其他疼痛相关病症时实现剂量控制。在本研究中，使用了两种来自标准化（CEX）栓剂的基质：可可脂和Witepsol H15。
对CEX进行了长达24个月的长期稳定性研究。使用高效液相色谱法测定∆-9-THC、大麻二酚（CBD）和大麻酚（CBN）的浓度。此外，还测定了提取物的水分含量、乙醇残留量和微生物纯度。评估了含CEX栓剂的药物性质，即含量均匀度、硬度、软化时间、总变形时间、崩解时间以及∆-9-THC、CBD和CBN的释放曲线，以便为药剂师制定最佳制备程序。
对CEX进行24个月的稳定性研究后，未观察到成分含量有超出规定要求的显著变化。发现含CEX的基于Witepsol H15的栓剂的崩解时间、总变形时间和硬度分别比用可可脂制成的栓剂更长和更高。体外研究表明，与用可可脂制备的栓剂相比，用Witepsol H15制备的栓剂表现出更好的∆-9-THC释放。
我们建议，在药房环境中以医用大麻栓剂形式配制处方药的药剂师，选择Witepsol® H15作为基质将获得更好的药物释放曲线。
