(W1230-03-17) Optimizing the Process Parameters for Utilizing Hot-Melt Extrusion Technology in the Development of Cannabidiol Nano-Structured Lipid Carriers

Purpose: Hot melt extrusion (HME) is used in the pharmaceutical field as a short and scale-up process for drug delivery and formulation development. This ongoing research aims to optimize this method for the scale-up production of cannabidiol nanostructured lipid carriers (CBD NLCs) to enhance its solubility. CBD NLCs were previously prepared in our lab by the hot homogenization method as an approach for CBD solubility and bioavailability enhancement. The lead CBD NLC formulation, which showed an increase in CBD solubility and oral bioavailability was selected to be prepared by HME.

Methods: HME was employed in the development of CBD NLC, Compritol^® 888ATO, sesame oil, and tween^® 80 were used as the solid lipid, liquid lipid, and surfactant, respectively. Initially, calibration curves were established for the peristaltic pumps which were responsible for injecting both the oil phase and the aqueous phase (comprising water and surfactant). Process 11 hot melt extruder (Thermo-Fisher Scientific, Karlsruhe, Germany) was used to prepare the CBD-NLC formulation. The oil phase, the solids (Compritol^® 888ATO CBD), and the aqueous phase were introduced in zones 1, 2, and 4 respectively. Three different screws speed were applied, 100 rpm, 200 rpm, and 300 rpm to test the impact of varying screw speed and shear force on the developed NLCs homogeneity and particle size. The prepared formulations underwent sonication for 10 minutes using a probe sonicator. The influence of different screws speed and sonication processes on particle size (PS), entrapment efficiency (EE), drug release, and stability were thoroughly investigated in the developed formulations which were coded as NLC 100-BS (before sonication), 100-AS (after sonication), 200-BS, 200-AS, 300-BS, and 300-AS.

Results: CBD NLCs were prepared using HME before and after probe sonication, CBD content was in the range from 94% to 100% under different conditions. Table 1 displays the particle size (PS), polydispersity index (PDI), and zeta potential (ZP) for the developed NLCs, the results showed an increase in the particle size following the prob sonication process, possibly due to, the enhancement in the system homogeneity, and CBD entrapment inside the lipids. These results supported by the EE %, as shown in figure 1, the results confirmed the higher EE for NLC100-AS, NLC 200-AS, and NLC 300-AS than NLC 100-BS, NLC200-BS, and NLC 300-AS. Additionally, EE in NLC 100-BS is higher than NLC 200-BS and NLC 300-BS, suggesting that higher speeds and the low residence time in the barrel impact the efficient mixing of the drug with other excipients. Figure 2 presents the drug release profiles of NLCs, CBD release was enhanced by the sonication step, likely due to the improved drug encapsulation within the lipid and stabilization by the surfactant. The release study was conducted in comparison to pure CBD. The result showed that the HPLC analysis of the samples withdrawn from pure CBD was below the limit of the HPLC detection which indicated that the CBD dissolution rate was notably enhanced for the prepared CBD NLCs as shown in Figure 2.

Conclusion: The presented study revealed the efficacy of employing HME as a short, and easy scale-up process for the development of CBD NLCs. The evaluation studies showed that there was an impact of the screw speed and sonication process on the developed NLCs. Additionally, the results revealed and supported the enhancement of CBD water solubility when formulated as NLCs.

References: Chokshi R, Zia H. Hot-melt extrusion technique: a review. Iranian journal of pharmaceutical research. 2004 Jan 31;3(1):3-16.
Tambe S, Jain D, Agarwal Y, Amin P. Hot-melt extrusion: Highlighting recent advances in pharmaceutical applications. Journal of Drug Delivery Science and Technology. 2021 Jun 1;63:102452.
Bhagurkar AM, Repka MA, Murthy SN. A novel approach for the development of a nanostructured lipid carrier formulation by hot-melt extrusion technology. Journal of pharmaceutical sciences. 2017 Apr 1;106(4):1085-91.


Figure 1. CBD EE % for the developed NLCs shows the effect of different parameters on the EE.


Figure 2. CBD release profile for the developed NLCs represents the effect of different screws speed and the sonication process on the drug release.


Table 1. PS, PDI, and ZP for the developed CBD NLCs using HME under different conditions.