QbD approach for the development of CBD-loaded polymeric micelles for oral delivery

As part of our studies dedicated to the development of new drug delivery systems of cannabidiol, (CBD) a main constituent of Cannabis sativa, we report on QbD approach for preparation and optimisation of polymeric micelles for oral delivery. To date, only one prescription medicine has been approved. Oral administration of cannabidiol has been reported to have two major drawbacks: very low water solubility (12 mg/L) and extensive first-pass metabolism. To overcome these limitations, the present study developed micelles made of Poloxamer 407 (P407) and D-α-tocoferolo polietilenglicole 1000 succinato (TPGS). P407 is a GRAS excipient, while TPGS has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. It has multiple advantages including high biocompatibility, enhancement of drug solubility, and improvement of drug permeation and inhibition of the activity of ATP dependent P-glycoprotein. The experimental design was carried out using D-optimal design; mixture process-variable (MPV) approach and mixture design were used for screening and optimization, respectively. Micelles loaded with CBD showed a size of 21.14±0.30nm, polydispersity index (PdI) of 0.040±0.004, recovery % of 98.24±2.52% and encapsulation efficiency % of 83.00±2.52%. Micelles loaded with CBD were evaluated for the stability in simulated gastrointestinal fluids in the presence of enzymes; a slight increase in PdI (0.280) was registered after intestinal dilution, while the size remained unchanged. A loss of up to 10% of CBD was observed in the simulated intestinal environment.