Title
Electrostatic Dry Powder Inhaler for Constant-Dose
Respiratory Drug Delivery
(BME-ECE-ME)
Technical
areas
(1) Pharmaceutical particle surface engineering design for improved drug
formulation, (2) Design of an electrodynamic dispersion system for
respiratory drug delivery process, and (3) Precision mechanical design of an
inhalation chamber with computer control
Customer’s
Project
Description
Project Summary:
Respiratory drug delivery (RDD) devices administer therapeutic aerosols via
pulmonary airways to treat asthma, COPD, cystic fibrosis, emphysema,
pulmonary hypertension, ARDS and other diseases. Such inhalation devices
are also emerging for the treatment of TB, lung cancer, diabetes, allergies,
viral infections, multiple sclerosis, hepatitis B and C, and osteoporosis. The
current respiratory delivery market is approximately $13 billion, and
continued growth is expected. Currently manufactured Dry Powder Inhalers
(DPI’s) do not meet many clinical needs. Only 10 to 15 percent of the active
drugs as emitted aerosol from the DPIs reach the targeted regions of the
lung. Reproducibility of the manufactured dosage may vary by as much as
20% due to manufacturing inconsistencies in microgrinding and random
mixing of drug powder with carriers (US FDA: Guidance to Industry: MDI
and DPI Drug Products)1. There is a need to develop new technology that
will provide far more reliable delivery with each dose for the current
formulations and new therapeutic drugs. Dose-to-dose variations and suboptimal delivery result in poor management of disease and wastage of
potentially expensive therapeutic agents.
Project Goal:
Develop a new Dry Powder Inhaler (DPI) device capable of delivering
metered doses of well-dispersed, carrier free, fine therapeutic aerosol, in a
wide range of patient inhalation flow rate (IFR) providing delivery with
dose-to-dose variability less than 5%.
Specific Aims:
1. Pharmaceutical particle surface engineering to (a) minimize forces
of cohesion of fine drug powders for better dispersion and free
flowing properties and (b) design of an electrostatic mixing process
for uniform blending of fine drug particles with coarse lactose
powder (used as an excipient) with optimum inter-particle forces of
adhesion to provide stability of the drug formulation and improved
dispersion efficiency,
2. Development and design of a piezoelectric- vibration assisted
electrodynamic dispersion device for producing aerosol of the drug
particles in the range from 0.1 to 5.0 µm in diameters for respiratory
drug delivery from the metered doses of drug-excipient blended
powders using a DPI device,
3. Evaluation of the respiratory drug delivery process via design and
construction of a mechanical inhalation chamber for testing the
aerosol formation of the surface-engineered drug particles with
electrodynamic dispersion at a different inhalation flow rates.
Analysis of the dispersion process and drug delivery efficiency will
include measurements of the size and electrostatic charge
ECE Department, Boston University
2/17/2016
distributions of the DPI emitted aerosol particles and dose-to-dose
variability,
4. Application of a laser based instrument for measuring particle size
and electrostatic charge distributions of particles, and
5. Design and development of a prototype of clinically viable Dry
Powder Inhaler (DPI) device to provide good consistency and longterm stability with user-friendly operation.
BME Students: (1) Design of a setup for particle surface engineering for
controlling adhesion between the drug particles (a model drug will be used
for convenience and safety) and the excipient powders (lactose), (2) Studies
on the respiratory drug delivery process, (3) Evaluation of different dry
powder inhaler devices for their dispersion and delivery properties as a
functions of the size distribution emitted aerosol particles at a wide range of
inhalation flow rates, and (4) Analysis of dose-to-dose variability for
different formulation of the drugs.
ECE Students: (1) Design and development of a piezoelectric vibration
assisted electrodynamic dispersion process, (2) Development of a model on
electrodynamic dispersion process, (3) Design of two electrostatic chargers
needed for mixing of drug and excipient powders by charging the powders
with opposite polarities, (4) Measurement of size and charge distributions of
the particles before and after charging, uniformity of mixing with
electrostatic mixing process and (5) Analyzing dispersion efficiency with
electrodynamic and piezoelectric vibration.
ME Students: (1) Design and construction of an electrostatic drug blending
process and comparing it with mechanical mixing with respect to the
uniformity of blending and the dispersion properties of the blended drug
particles (2) Development of a mechanical inhalation chamber to simulate
inhalation at different inhalation flow rates, and (3) Evaluation of test Dry
Powder Inhaler (DPI) devices using the inhalation chamber.
Note: Lactose powder (milk powder) as used in the pharmaceutical
industries and a model drug powder such as albuterol sulfate or caffeine
powder will be used. Appropriate precaution will be included in the design
of apparatus for safety and containment.
Deliverables Development of (1) processes for surface engineered drug particles, (2) an
electrostatic process for ordered mixing of drug and excipient powders, (3)
electrodynamic dispersion process for high efficiency respiratory drug
delivery, (3) a computer-controlled mechanical inhalation chamber for
evaluation of stability and dose-to-dose variability of DPI devices.
Customer’s
Contact
Information
Customer’s
Supplied
Items
Prof. M. K. Mazumder
ECE
Prof. Andrew Jackson
Prof. Vinod Sarin
BME
ME
mazumder@bu.edu
ajax@bu.edu
sarin@bu.edu
All materials and supplies needed for the design and development of the
processes outlined above will be provided from the CIMIT Grant.
ECE Department, Boston University
2/17/2016