The therapeutic effect of the Cannabis plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. Although prescription of medicinal Cannabis for various conditions constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability, and efficacy. Herein, a long-acting formulation in the form of melt-printed polymeric microdepots for full-spectrum cannabidiol (CBD)-rich extract administration is described. When injected subcutaneously in mice, the microdepots facilitate sustained release of the encapsulated extract over a two-week period. The prolonged delivery results in elevated serum levels of multiple, major and minor, phytocannabinoids for over 14 days, compared to Cannabis extract injection. A direct analysis of the microdepots retrieved from the injection site gives rise to an empirical model for the release kinetics of the phytocannabinoids as a function of their physical traits. As a proof of concept, we compare the long-term efficacy of a single administration of the microdepots to a single administration of Cannabis extract in a pentylenetetrazol-induced convulsion model. One week following administration, the microdepots reduce the incidence of tonic-clonic seizures by 40%, increase the survival rate by 50%, and the latency to first tonic-clonic seizures by 170%. These results suggest that a long-term full-spectrum Cannabis delivery system may provide new form of Cannabis administration and treatments.
Introduction: As the medical use of Cannabis is evolving there is a greater demand for high-quality products for patients. One of the main steps in the manufacturing process of medical Cannabis is drying. Most current drying methods in the Cannabis industry are relatively slow and inefficient processes. Materials and Methods: This article presents a drying method based on solid-state microwave (MW) that provides fast and uniform drying, and examines its efficiency for drying Cannabis inflorescences compared with the traditional drying method. We assessed 67 cannabinoids and 36 terpenoids in the plant in a range of drying temperatures (40°C, 50°C, 60°C, and 80°C). The identification and quantification of these secondary metabolites were done by chromatography methods. Results: This method resulted in a considerable reduction of drying time, from several days to a few hours. The multiple frequency-phase combination states of the system allowed control and prediction of moisture levels during drying, thus preventing overdrying. A drying temperature of 50°C provided the most effective results in terms of both short drying time and preservation of the composition of the secondary metabolites compared with traditional drying. At 50°C, the chemical profile of phytocannabinoids and terpenoids was best kept to that of the original plant before drying, suggesting less degradation by chemical reactions such as decarboxylation. The fast-drying time also reduced the susceptibility of the plant to microbial contamination. Conclusion: Our results support solid-state MW drying as an effective postharvest step to quickly dry the plant material for improved downstream processing with a minimal negative impact on product quality.
Over the last several decades, 3D printing technology, which encompasses many different fabrication techniques, had emerged as a promising tool in many fields of production, including the pharmaceutical industry. Specifically, 3D printing may be advantageous for drug delivery systems, systems aiming to improve the pharmacokinetics of drugs. These advantages include the ease of designing complex shapes, printing of drugs on demand, tailoring dosage to the specific needs of the patient and enhancing the bioavailability of drugs. This paper reviews the most recent advancements in this field, presenting both the abilities and limitations of several promising 3D printing methods.
Achieving homogeneity and reproducibility in the size, shape, and morphology of active pharmaceutical ingredient (API) particles is crucial for their successful manufacturing and performance. Herein, we describe a new method for API particle engineering using melt-jet printing technology as an alternative to the current solvent-based particle engineering methods. Paracetamol, a widely used API, was melted and jetted as droplets onto various surfaces to solidify and form microparticles. The influence of different surfaces (glass, aluminum, polytetrafluoroethylene, and polyethylene) on particle shape was investigated, revealing a correlation between substrate properties (heat conduction, surface energy, and roughness) and particle sphericity. Higher thermal conductivity, surface roughness, and decreased surface energy contributed to larger contact angles and increased sphericity, reaching a near-perfect micro-spherical shape on an aluminum substrate. The integrity and polymorphic form of the printed particles were confirmed through differential scanning calorimetry and X-ray diffraction. Additionally, high-performance liquid chromatography analysis revealed minimal degradation products. The applicability of the printing process to other APIs was demonstrated by printing carbamazepine and indomethacin on aluminum surfaces, resulting in spherical microparticles. This study emphasizes the potential of melt-jet printing as a promising approach for the precise engineering of pharmaceutical particles, enabling effective control over their physiochemical properties.
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