eBook: Formulation of Dry Powder Inhaler - 32
chemotherapeutic APIs were chosen as model compounds:
PTX and CP. In addition, the EGFR-inhibitor
ERL was selected as a third model system, which
could potentially be relevant to patients whose tumors
have EGFR mutations.
From a therapeutic standpoint, the local treatment
of lung disease, particularly of lung cancer, using dry
powder inhalers specifically has many potential patient
benefits, including:
1. Reduced dose;
2. Reduced systemic side effects;
3. Avoidance of cold chain storage
requirements;
4. Simple, at-home administration;
5. Reduced cost of treatment.
These advantages are discussed in greater detail in
recent publications17,25,26
and review articles.27
The
combination therapies exemplified were chosen
from approved cancer therapies and were intended
to serve as a proof of concept which could help
patients who are dealing with a challenging disease.
For chemotherapy in particular, local treatment by
inhalation has many remaining hurdles to its implementation,
although dry powder inhalers have
the potential to address some of these issues.24
In
the current standard of care, a late-stage lung cancer
patient receives both CP and BEV by IV infusion
at recurring in-clinic appointments. Although this
work is at an early stage, the vision of having a single
treatment administered non-invasively at home by
dry powder inhaler is a compelling one for patients.
Conclusions
This article demonstrated the simul-spray drying
technology in which spray-dried particles of
two different compositions are atomized into the
dryer simultaneously with the use of two separate
nozzles, forming a uniform powder blend. Simulspraying
was used in this work to manufacture
combination therapies for inhalation which contain
BEV and small-molecule cancer therapies: ERL,
PTX, and CP. The resulting powders achieved their
target drug concentration, good aerosol properties
for delivery to the lung, and preserved anti-VEGF
bioactivity. For lung cancer, inhaled combination
therapies could locally treat this complex disease,
easing patient compliance, reducing the dose, and
limiting the exposure of healthy tissue to toxic
compounds. More generally, a simul-spraying technique
can be used to prepare combination inhalation
therapies with otherwise incompatible APIs.
The process could eliminate additional blending
operations on poor-flowing inhalation powders
and potentially shorten development timelines for
combination inhalation products.
Supplementary Materials: The following supporting
information can be downloaded at: https://
www.mdpi.com/article/10.3390/pharmaceutics14061130/s1.
Additional information on formulation
and solvent selection, aerodynamic particle
size distributions, detailed interpretation of PXRD
and DSC results, experimental details for zero intercept
method of drug quantification by absorbance,
additional details on water content measurement,
and GC headspace instrument parameters. Figure
S1: Aerodynamic particle size distribution for ERL
1:2, PTX 1:1 and CP 1:1 formulations. Figure S2: PXRD
of PTX 1:5, 1:2, 1:1, 2:1 formulations and controls.
Figure S3: PXRD of ERL 1:2, 1:1 formulations and
controls. Figure S4: 2:1 formulations and controls.
Figure S5: DSC thermograms for CP formulations
and controls. Figure S6: 2nd derivative spectra for
BEV and CP standard curves with dashed lines showing
where each component was quantified. Figure
S7: 2nd derivative spectrum of a solution containing
32
http://https://
http://www.mdpi.com/article/10.3390/pharmaceu
eBook: Formulation of Dry Powder Inhaler
Table of Contents for the Digital Edition of eBook: Formulation of Dry Powder Inhaler
eBook: Formulation of Dry Powder Inhaler - 1
eBook: Formulation of Dry Powder Inhaler - 2
eBook: Formulation of Dry Powder Inhaler - 3
eBook: Formulation of Dry Powder Inhaler - 4
eBook: Formulation of Dry Powder Inhaler - 5
eBook: Formulation of Dry Powder Inhaler - 6
eBook: Formulation of Dry Powder Inhaler - 7
eBook: Formulation of Dry Powder Inhaler - 8
eBook: Formulation of Dry Powder Inhaler - 9
eBook: Formulation of Dry Powder Inhaler - 10
eBook: Formulation of Dry Powder Inhaler - 11
eBook: Formulation of Dry Powder Inhaler - 12
eBook: Formulation of Dry Powder Inhaler - 13
eBook: Formulation of Dry Powder Inhaler - 14
eBook: Formulation of Dry Powder Inhaler - 15
eBook: Formulation of Dry Powder Inhaler - 16
eBook: Formulation of Dry Powder Inhaler - 17
eBook: Formulation of Dry Powder Inhaler - 18
eBook: Formulation of Dry Powder Inhaler - 19
eBook: Formulation of Dry Powder Inhaler - 20
eBook: Formulation of Dry Powder Inhaler - 21
eBook: Formulation of Dry Powder Inhaler - 22
eBook: Formulation of Dry Powder Inhaler - 23
eBook: Formulation of Dry Powder Inhaler - 24
eBook: Formulation of Dry Powder Inhaler - 25
eBook: Formulation of Dry Powder Inhaler - 26
eBook: Formulation of Dry Powder Inhaler - 27
eBook: Formulation of Dry Powder Inhaler - 28
eBook: Formulation of Dry Powder Inhaler - 29
eBook: Formulation of Dry Powder Inhaler - 30
eBook: Formulation of Dry Powder Inhaler - 31
eBook: Formulation of Dry Powder Inhaler - 32
eBook: Formulation of Dry Powder Inhaler - 33
eBook: Formulation of Dry Powder Inhaler - 34
eBook: Formulation of Dry Powder Inhaler - 35
eBook: Formulation of Dry Powder Inhaler - 36
eBook: Formulation of Dry Powder Inhaler - 37
eBook: Formulation of Dry Powder Inhaler - 38
eBook: Formulation of Dry Powder Inhaler - 39
eBook: Formulation of Dry Powder Inhaler - 40
eBook: Formulation of Dry Powder Inhaler - 41
eBook: Formulation of Dry Powder Inhaler - 42
eBook: Formulation of Dry Powder Inhaler - 43
eBook: Formulation of Dry Powder Inhaler - 44
eBook: Formulation of Dry Powder Inhaler - 45
eBook: Formulation of Dry Powder Inhaler - 46
eBook: Formulation of Dry Powder Inhaler - 47
https://www.nxtbookmedia.com