Optimization and Evaluation of Cannabis-Based Magistral Formulations: A Path to Personalized Therapy.

Abstract

Introduction: 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 Cannabis extractum normatum (CEX) were used: cocoa butter and Witepsol^® H15.

Materials and methods: 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.

Results and discussion: 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.

Conclusions: 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.