PHARMA FOCUS: CANNABIS
Cannabinoid molecules and their love of lipid excipients The generic term “cannabinoids” refers to different active pharmaceutical ingredients, the most popular being cannabidiol (CBD) which is non-psychoactive, and delta-9 tetrahydroxy cannabinol (THC) with psychoactive properties. With rapidly evolving regulations in many countries, a boom in cannabinoid products is observed. However, due to their physico-chemical properties, these molecules are very difficult to formulate. This article showcases how lipid excipients can solve cannabinoid formulation challenges with a particular focus on oral and topical dosage forms.
C
annabinoids cumulate many drawbacks such as low aqueous solubility, oxidation and temperature sensitivity, and high first-pass metabolism.1 Although cannabinoids have extremely low aqueous solubility and high lipophilicity (LogP around 6 to 8), they also have exceptional solubility in lipid excipients as shown in Table 1. Therefore, with lipid excipients, solubility is not a limitation.
"Although formulating with cannabinoids can be highly challenging, it is possible to overcome the various hurdles using lipid excipients" These molecules are prone to oxidation; consequently, minimising the incorporation of air while mixing and adding antioxidants are compulsory to prevent molecule degradation. Because they are also extremely sensitive to temperature, cannabinoids must be handled and stored at the lowest temperature possible to stop them from being broken down.
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Table 1: Solubility of CBD and THC in lipid excipients (expressed in mg/mL for liquid excipients and mg/g for semi-solid or solid excipients)
Excipient tradename
Chemical name
Capryol® 90
Propylene glycol monocaprylate (Type II, monoesters >90%) NF
Gelucire® 44/14
CBD (mg/mL or mg/g)
THC (mg/mL or mg/g)
548
496
Lauroyl macrogol-32 glycerides EP Lauroyl polyoxyl-32 glycerides NF
>255
125
Gelucire® 48/16
PEG-32 stearate (type I) NF / EP pending
>300
>500
Labrafac™ Lipophile WL 1349
Triglycerides medium-chain EP Medium-chain triglycerides NF
410
421
Labrafac® MC60
Glycerol monocaprylocaprate (type I) EP Glyceryl monocaprylocaprate (Type I) NF
418
496
Labrafac™ PG
Propylene glycol dicaprylocaprate EP Propylene glycol dicaprylate/dicaprate NF
506
> 500
Labrafil® M 1944 CS
Oleoyl macrogol-6 glycerides EP Oleoyl polyoxyl-6 glycerides NF
421
454
Labrasol® Labrasol® ALF
Caprylocaproyl macrogol-8 glycerides EP Caprylocaproyl polyoxyl-8 glycerides NF
588
422
Lauroglycol™ FCC
Propylene glycol monolaurate (Type I, monoesters >45%) EP / NF
471
477
Maisine® CC
Glycerol monolinoleate EP Glyceryl monolinoleate NF
338
>500
Plurol® Oleique CC 497
Polyglyceryl-3 dioleate NF
Transcutol® P Transcutol® HP
Highly purified diethylene glycol monoethyl ether EP/NF
USP descriptor for solubility:
274
>500
>530
434
Very soluble >500 mg/mL
Freely soluble 100-500 mg/mL
