BENUVIA MANUFACTURING
pMDI CAPABILITIES
WHAT IS A pMDI?
ADVANTAGES OF A pMDI
More Efficient and Safer Alternative to Vaping, Smoking, or Oral Dosage Forms
Direct to Lung Delivery - Fast Onset
No First Pass Metabolism
No Additives or Combustion Byproducts
Delivers a Consistent, Precise Metered Dose
Tolerant of Environmental Conditions and has a Long Shelf Life (No Exposure to Oxygen, Light, or Moisture)
| Smoking/ Vaping | pMDI | |
|---|---|---|
| Amount of Active Ingredient Delivered | Varies - 20-70% (remainder lost through combustion and/ or side-stream smoke) | Current test results show each inhalation is within 93-107% of label claim (FDA requires 80-120%) |
| Compounds Delivered to the Lung | Estimated 7,000+ various compounds in smoke (including carcinogens) | Active Ingredient(s) Only |
| Consistency of Dose | Varies by plant Strain, Temperature of combustion, inhalation pattern, external condition, etc ... | Minimal Variability - Each inhalation consistent with Label Claim |
| Cannabinoid | Dose | Route of Administration | Cmax | Tmax |
|---|---|---|---|---|
| CBD1 | 1.6 mg | IV Injection | 22 ng/mL | 4 min |
| CBD1 | 0.696 mg (based on 45% respirable fraction from 1.6 mg dose) | Inhalation | 7 ng/mL | 5 min |
| CBD2 | 40 mg | Oral (cookie) | 5.5 ng/mL | 1 hr |
| CBD3 | 10 mg | Sublingual drops (GW Pharma) | 1.05-2.58 ng/mL | n/a |
| CBD3 | 10 mg | Oral Solution (GW Pharma) | 2.47 ng/mL | n/a |
| THC2 | 10 mg | Oral (brownie) | 1.0 ng/mL | 1 hr |
| THC2 | 50 mg | Oral (brownie) | 3.3 ng/mL | 2.4 hrs |
TESTING AND REGULATORY REQUIREMENTS
CURRENT CANNABIS INDUSTRY REQUIREMENTS
- Potency / Cannabinoid Profile
- Terpene Profile
- Pesticides
- Solvents
- Microbiological / Mycotoxins
- Heavy Metals
- Water Activity
FDA REQUIREMENTS FOR pMDI PRODUCTS
- Dose Content Uniformity
- Aerodynamic Particle Size Distribution
- Valve Delivery
- Total Contents
- Related Substances / Degradants / Impurities
- Spray Pattern / Plume Geometry
- Ethanol Content
- Moisture Content
- Leak Rate
- Net Contents
Dose Content Uniformity
The pMDI must delivery a consistent dose with every actuation, throughout the life of the product
Aerodynamic Particle Size Distribution
The active ingredient must be properly sized and distributed within the spray plume to be delivered past the terminal bronchioles to the gas exchange region of the deep lung
Assay
The delivered active ingredient should be highly purified cannabinoid(s) to ensure quality (99%+ is ideal)
TESTING CRITERIA
FIRST TIER – 10 UNITS, 1 DOSE
1. The amount of drug substance is not outside 80-120% of Target Delivered Dose (TDD) for more than one of ten determinations.
2. None of the determinations are outside 75-125% of the TDD.
3. The mean is not outside 85-115 percent of TDD.
SECOND TIER – 20 UNITS, 1 DOSE (may be used if 2 and 3 are met above)
1. The amount of drug substance is not outside 80-120% of Target TDD for more than three of thirty determinations.
2. None of the determinations are outside 75-125% of the TDD.
3. The mean is not outside 85-115 percent of TDD.
TESTING APPARATUS
AERODYNAMIC PARTICLE SIZE DISTRIBUTION (APSD)
There is US FDA Guidance for the pharmaceutical industry which lays out the criteria for an acceptable inhalation product:
It is not considered adequate to characterize the APSD in terms of the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) alone, or to limit the characterization only to fine particle mass or fine particle fraction.
Acceptance criteria should be proposed based on the amount of drug deposited on various stages of the equipment.
Applicants should propose acceptance criteria for groupings of consecutive stages rather than proposing an acceptance criterion for each individual stage. In most cases, three or four groupings should be sufficient to characterize the APSD adequately.
The mass balance must be between 85 and 115% of the TDD