The relatively recent discussion about legalizing cannabis has resulted in numerous case studies and field reports, whichdescribe the beneficial effects of cannabis on human health. However, theyusuallydo not fulfil the stringent requirements for an approval by medicinal authorities.The result is a kind of “grey zone”, mainly of OTC products with either an unqualified or not clarified approval status. Machine manufacturers like Syntegon Technology can help make medical grade cannabis available and, above all, safe for patients. One of the most important requirements is a profound expertise of manufacturing processes.
Although it is important to have good secondary packaging machines and processes available, this is not the big issue. Regulatory discussions mainly evolve around the manufacturing process itself. And this, in turn, concerns the dosage form of medical cannabis or marihuana.Currently, the majority of medical marihuana is sold as buds or tinctures. This dosage form has the immanent risk ofthe biological product showing large variations in terms of quality and thus API content between batches.These variations lead to the trend towards more controlled or even synthetic pharmaceutical grade sources and dosage forms. Hence, a significant market share will be going into more precisely dosed tablets and capsules.
Highly accurate liquid filling
Thechemical and physical properties of the main ingredients – THC and CBD – make it rather difficult to formulate oral medicines such as capsules. Both molecules are highly lipophilic, i.e. not soluble in water. Hence, so-called nanoemulsions have already been developed. They are supposed to improve the poor solubility and lead to a much better absorption in the intestine. However, the main way of use is still smoking. The ingredients of the plant extract need to be decarboxylized to have a medicinal effect in the human body. On the other hand, medicines need to maintain a narrow range of critical parameters such as content uniformity.
A possibility to bypass the obstacles of formulating solid dosage forms is to fill oily liquids or emulsions into hard shells. This requires a highly accurate liquid filling station, which can be found in the GKF hard capsule filling machine series from Syntegon. The basis is a high-precision pump, which doses according to volumetric adjustment. Depending on the viscosity of the formulation, an accuracy of 2.5% relative standard deviation (RSD) can be achieved for the filling process; some products even run below 1% RSD. This is essential especially for clinical trial material and proven in extensive test runs with liquids derived from the medical grade cannabis plant. Here the limits were set at +/- 3 % RSD. The most important feature is the pullback of liquid in the filling nozzles, which avoid drops at the end of the filling process. Furthermore, splashes are avoided by bottom-up filling.
Capsule filling parameters
The station has two separated heating or cooling circuits, which enable the accurate tempering of temperature-critical medicinal products. Some formulations have a very high viscosity at ambient temperature and need to be heated up to a certain level to make them fillable as a liquid. The GKF systems can ensure +/- 1 °C in the product hopper, as well as in the filling block with the filling nozzles.The servo-driven filling pistons and adaptable nozzle diameter make it possible to minimize or even eliminateleakagesfor most viscosities with a normal processing range from 100 up to 12,000 cP (centipoise). For instance, in one trial series temperature was set at 50 °C and had to be kept in a range of +/- 5 °C. This temperature profile was logged automatically in the batch report of the machine control in order to demonstrate the smooth process.
To prevent the loss of valuable product and to keep the machine clean, it has a “no capsule no filling” feature, which ensures that the filling process is only started when both capsule cap and body are in place.The batch report and audit trail function of the control software ensure a reliable and auditable documentation of the production process.In addition to its high flexibility, a strong focus of this liquid product filling technology is on the cleanability of the machine parts and stations, amongst other reasons to avoid product carry-over.
Hard capsules and tablets
As an alternative to liquid filling, powdery plant extracts can also be filled into hard capsules on all GKF machines as a standard process. Moreover, tablet compression machines are also available to process medical grade cannabis products in solid formulations.With pharma laboratories and customer service centers around the world, Syntegon Technology already has equipment and experts in place. In fact, companiesaround the globe are already processingor piloting formulations with active ingredients derived from the medical grade cannabis plant on capsule filling and tablet compression machines from Syntegon Technology. Due to confidentiality agreements,no details can be disclosed to date.
Althoughmost medicinal products derived from medical grade cannabis still have a long way to go, experience from current projects and other successful innovations show that it is highly beneficial for formulation developers to team up with machine building companies at a very early stage. On the one hand, a lot of the required technologies already exist. On the other hand, it is never too early to develop new processes and control mechanisms for future requirements. Syntegon Technology is looking forward to shaping this future together with its customers and to getting new products to the market. [Anchor]