BENUVIA MANUFACTURING

pMDI CAPABILITIES

WHAT IS A pMDI?

ADVANTAGES OF A pMDI

Q

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/ VapingpMDI
Amount of Active Ingredient DeliveredVaries - 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 LungEstimated 7,000+ various compounds in smoke (including carcinogens)Active Ingredient(s) Only
Consistency of DoseVaries by plant Strain, Temperature of combustion, inhalation pattern, external condition, etc ...Minimal Variability - Each inhalation consistent with Label Claim
CannabinoidDoseRoute of AdministrationCmaxTmax
CBD11.6 mgIV Injection22 ng/mL4 min
CBD10.696 mg (based on 45% respirable fraction from 1.6 mg dose)Inhalation7 ng/mL5 min
CBD240 mgOral (cookie)5.5 ng/mL1 hr
CBD310 mgSublingual drops (GW Pharma)1.05-2.58 ng/mLn/a
CBD310 mgOral Solution (GW Pharma)2.47 ng/mLn/a
THC210 mgOral (brownie)1.0 ng/mL1 hr
THC250 mgOral (brownie)3.3 ng/mL2.4 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