Detection and Identification of an Unknown Impurity in Ephedrine HCl 5 mg/mL Cyclic Olefin Syringes: Formulation Development.

An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already.

Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment.

The application of cannabis products in oncology receives interest, especially from patients. Despite the plethora of research data available, the added value in curative or palliative cancer care and the possible risks involved are insufficiently proven and therefore a matter of debate. We aim to give a recommendation on the position of cannabis products in clinical oncology by assessing recent literature. Various types of cannabis products, characteristics, quality and pharmacology are discussed. Standardisation is essential for reliable and reproducible quality. The oromucosal/sublingual route of administration is preferred over inhalation and drinking tea. Cannabinoids may inhibit efflux transporters and drug-metabolising enzymes, possibly inducing pharmacokinetic interactions with anticancer drugs being substrates for these proteins. This may enhance the cytostatic effect and/or drug-related adverse effects. Reversely, it may enable dose reduction. Similar interactions are likely with drugs used for symptom management treating pain, nausea, vomiting and anorexia. Cannabis products are usually well tolerated and may improve the quality of life of patients with cancer (although not unambiguously proven). The combination with immunotherapy seems undesirable because of the immunosuppressive action of cannabinoids. Further clinical research is warranted to scientifically support (refraining from) using cannabis products in patients with cancer.