The galenic formulation is a part of pharmaceutics, necessary in order to transform any kind of plant into a customized dose and form of medication, which follows a precise manufacturing practice, in order to guarantee quality and efficacy to the patient.

In Italy, on November 9th, 2015 the government launched a project for cannabis-based galenic formulations of vegetal origin[1], entrusting the entire process to pharmacists, and alongside approving a law, which regulates the national production of cannabis and its derived products.

Access to medical cannabis through the pharmacy

Pharmacists, with the patient’s medical prescription, need to make a formal request for medical cannabis to the military pharmaceutical facility (Stabilimento Farmaceutico Militare) or to other entities recognized by the government[2]. Only after having followed every necessary bureaucratic formalism, they will be allowed to manufacture galenic formulation, according to the Good Manufacturing Practices (GMP)[3], and they can provide cannabis or its derived products, for oral and inhalator use, following the doctor’s prescription.

Nowadays, the supply of cannabis to pharmacies is subjected to the dispatch of specific strains of Cannabis Sativa L:

  • FM2: THC (5 ~ 8%) and CBD (7.5% ~ 12%) (Sativa strain)
  • BEDROCAN: THC (19 ~ 21%) and CBD < 1% (Sativa strain)
  • BEDIOL: THC (6.5%) and CBD (8%) (Sativa strain)
  • BEDROLITE: THC (< 1%) and CBD (9%) (Sativa strain)
  • BEDICA: THC (14%) and CBD (< 1%) (Indica strain)

Pharmaceutical manufacture of cannabis-based drugs

Once the pharmacist receives the flower, he is in charge of the manufacturing of the products. The formulation depends on the strain used and on the form prescribed by the doctor. In this way, the pharmacist can formulate different forms of medicines based on cannabis, depending on the different ways of administration: oral or inhalation[4].

Titration of pharmaceutical cannabis-based products

With the aim to ensure the quality of the product, the government requires the “titration of the active principle/s for each galenic formulation, through sensitive and specific methods, such as liquid or gas chromatography, coupled with the mass spectrometry. In addition, the extraction method used has to be authorized by the current law”.

Extraction methods of cannabinoids

In order to work with inflorescences, pharmacists have to work with extractions in oil and/or in other alcoholic solvents.

The SIFAP – Italian Society of Compounding Pharmacists (Società Italiana Farmacisti Preparatori)[5]  – created a technical group, in 2016, aimed to elaborate shared procedures for the oil-based extraction, with the purpose to standardize the process and to reproduce its results in the entire national territory (Italian and European).

The group started conducting two studies, in collaboration with the University of Milan and with the Università degli Studi di Napoli, Federico II, aimed to select an extractive methodology for obtaining the best extraction of THC and other cannabinoids but, in the same time, saving the entire composition of the phytocomplex.

Independently from the extractive method, the group highlighted that is necessary to undergo the extraction through a heating process, which is called decarboxylation process. The importance of heating the preparation rises because all phytocannabinoids appear in the plant in their acid form. Nonetheless, not all phytocannabinoids interact with CB1 and CB2 receptors, but those that bond them are in their neutral form, non-carboxylated, non-acid form.

Accepted method: maceration of cannabis in oil

The only method, recognized by the SIFAP Group, imposes the maceration of cannabis flowers into vegetal oils, such as olive or sunflower oil for example.

At the end of the process, maintaining the same volume of the solution, the initial concentration of cannabinoids of the flower will then reduce almost to one-tenth within the solution, leaving a minimal concentration in the final product.

In this way, differently to what affirmed by the SIFAP Group, the objective to maintain the major possible content of THC has not been achieved.

Alternative method: extraction in alcohol

With further attention on the extraction methods, we can notice that the concentrations of phytocannabinoids strongly depend on the solvent used, because of its physical characteristics. For this reason, we want to take into consideration another alcoholic solvent, the ethanol, which is considered one of the best and less toxic alcoholic solvents.

Such as during the maceration in olive oil, macerating cannabis flowers in ethanol, all phytocannabinoids will separate from the vegetal mass and will solve into the solvent. Nonetheless, once the solvent comes in contact with air, it starts an evaporation process, that will never occur when using oils as solvents.  At the end of the process, the final remaining substance is the pure extract, which contains the entire phytocomplex. Furthermore, if we indirectly heat the solvent, it also undergoes the decarboxylation process, which will accelerate the evaporation of the excess solvent and will transform the majority of cannabinoids into their respective neutral forms. In this way, the extraction reduces its volume, with the following increase in the concentration of each cannabinoid present in it.

This extract contains the whole phytocomplex and can be properly titrated in all its purity, in order to obtain its exact cannabinoids composition.

Results of extracting cannabis in alcohol

The precise amount of extraction obtainable with this method mainly depends on the strain of the plant and on the solvent used. Though only once the rosin has been extrapolated, it is possible to measure its exact cannabinoids composition.

Let’s try to provide a concrete example and we will round number, to make the calculations easier to carry out.

We suppose to obtain 100gr of extract. Even if we started taking a cannabis strain with a THC content of 10%, after the evaporation of the solvent and the loss of the vegetable mass, the final extract will present a remarkable increase in concentration. In order to know up to which volume the extract concentration has increased, it is necessary to proceed with the analysis of the product, through liquid or gas chromatography.

Assuming that in this phase the extract presents a THC content of 30%, we have so obtained 30gr of THC. Since a THC oil at 10% has 1gr of THC within 10ml of solvent, if we solve 3.3gr of our complete extraction in 10ml of olive oil, we will be able to obtain an oil with the wanted THC content, according to what the doctor had prescribed.

Noticeable, a big amount of extract will remain in the hands of the pharmacist that can be able to produce more medications, specific for each patient, as it has already been uniformly controlled and standardised.

Conclusion

Even if we used pure explanatory calculations, not necessarily precise, the aim of this article is to clarify how this alternative process can provide a more controllable and standardised product, that would permit to the pharmacist to elaborate different products, specific for each patient, but uniformly controlled. Moreover, this will permit the government to obtain all the needed information, regarding these treatments and their efficacy on different condition and person, and regarding the exact composition of every product released by the pharmacy.

It is of vital importance that all pharmacists are aware of all possible cannabis manufactures, of how to control the final results and of how to standardise procedures and controls, chemical and bureaucratic.

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Did you like the post? Give us some feedback! This post has been done based on existent research to the date of publication of the article. Due to the increase in studies based on medical cannabis, the information provided can vary over time and we’ll keep informing in further writings.

[1] Decreto Ministeriale, 9 novembre 2015, Gazzetta Ufficiale della Repubblica Italiana

[2]Riferimenti normativi sulla coltivazione della cannabis in Italia” (30 maggio 2018), Camera dei deputati.

[3]Guide for GMP Documentation and Records

[4]  Corso Superiore SIFO in farmacia clinica – Prof. Puglisi Giovanni (Ottobre 2017) “Cannabis per uso terapeutico: la dispensazione in farmacia”

[5] Società Italiana Farmacisti Preparatori (Settembre 2016) “SIFAP propone un metodo per l’Estrazione oleosa di infiorescenze femminili di Cannabis

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Manufacture of cannabis-based pharmaceutical products: from a plant to a medication
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Manufacture of cannabis-based pharmaceutical products: from a plant to a medication
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Nowadays, countries like Italy are entrusting the formulation of cannabis-based products to pharmacies, following some manufacturing procedures.
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Kalapa Clinic
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