(M1030-06-32) Aerodynamic Performance of Spray Dried Cannabidiol Powder for Efficient Pulmonary Delivery

Purpose: Expanding clinical research into the therapeutic value of cannabinoids requires pharmaceutically acceptable, standardized dosage forms that can supplant the joints, “bongs”, and heat-based vaporizers historically used to study these compounds. Emergent pharmacokinetics data on a dry powder inhaler (DPI) demonstrated substantial benefits in bioavailability and T_max compared to CBD administered per os (PO) [1]. One of the challenges facing developers of inhalable forms is that the highly bitter flavor [2] of CBD irritates the upper airways which can elicit a cough response when sufficient drug quantities interact with sensory receptors present in the oropharyngeal region. This study characterizes the aerosol performance of FP001, a CBD powder engineered to bypass the upper airways and to maximize lung delivery.

Methods: An aqueous based emulsion consisting of CBD isolate (~ 99 %) derived from hemp, leucine, trehalose, DSPC, and citric acid, was spray dried using a Mobile Minor (GEA Niro, Düsseldorf, Germany) operated in an open loop configuration to produce powder containing 10 % CBD by weight. Powder was filled into size 3, HPMC capsules (VCaps Plus; Capsugel, Morristown, New Jersey) to a target fill weight of 10 mg using a dosator type filling apparatus (LM-14; M&O Perry, Corona, CA), producing a packaged strength of 1 mg CBD per capsule. A gravimetric method for Anderson Cascade Impactor (ACI; Copley Scientific, Nottingham, UK) was used to assess aerodynamic performance of the powder. Capsules were placed into a breath powered Monodose inhaler (RS01 m.7, Berry Healthcare, Osnago, IT) and actuated using a programmable flow controller (TPK2000; Copley Scientific). For comparison to RLS103 powder performance with the Dreamboat™ inhaler (MannKind Corporation, Westlake Village, CA), ACI tests were carried out with the USP Induction Port and operated at a flow rate of 28.3 L/min, which corresponds to a 0.8 kPa pressure drop across the Monodose inhaler. The total air flow volume was 4 L per test. Results reported include the emitted dose (ED), fine particle dose (FPD; stages 2-6), mass median aerodynamic diameter (MMAD), the geometric standard deviation (GSD), and drug retention in the device and package and the induction port. The FP001 results reported are the average of three capsule tests.

Results: Aerodynamic performance testing of capsules filled with FP001 CBD powder resulted in a 0.91 mg (91 % of the capsule fill) Emitted Dose and a 0.69 mg Fine Particle Dose was. Device and capsule retention totaled 0.9 mg (9 %). The MMAD was 2.8 µm and the GSD was 1.7. ACI powder mass balance was acceptable, with 7.3 mg of powder, equaling 86 % of the Emitted Mass, recovered on the impactor stages. Powder retained in the inlet port was 0.7 mg (0.07 mg CBD), representing 7 % of the capsule contents. (Figure 1). Despite a 1.1 mg higher RLS103 packaged strength (2.1 vs 1.0 mg CBD), the FPD of FP001 was 17 % greater than that of RLS103. Differences in Induction Port powder retention contributed to this result, with 35 % (4.3 mg) of the RLS103 delivered dose compared to 8 % (0.7 mg) for FP001. Normalized to nominal CBD dose, this equates to a 34-fold performance difference in terms of Induction Port retention.

Conclusion: This study provides aerosol performance of a CBD powder engineered for inhalation as a dry powder. FP001 dispersed by the Monodose inhaler exhibited excellent aerodynamic performance, with high ED and FPD. Presuming that Induction Port retention is indicative of powder deposition in the upper airways, then FP001 may offer researchers a DPI platform that reduces the risk of cough response and throat irritation while maximizing delivery efficiency.

References: 1. Devinsky O, Kraft K, Rusch L, Fein M, Leone-Bay A. Improved Bioavailability with Dry Powder Cannabidiol Inhalation: A Phase 1 Clinical Study. J Pharm Sci. 2021 Dec;110(12):3946-3952. doi: 10.1016/j.xphs.2021.08.012. Epub 2021 Aug 13. PMID: 34400185.
2. Stella B, Baratta F, Della Pepa C, Arpicco S, Gastaldi D, Dosio F. Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain. Drugs. 2021 Sep;81(13):1513-1557. doi: 10.1007/s40265-021-01579-x. Epub 2021 Sep 4. PMID: 34480749; PMCID: PMC8417625.

Figure 1. Aerodynamic performance of FP001 and RLS103 (data adapted from O. Devinsky et al. [1])