Medical and Pharmaceutical Aerosols - Aerosols: Measurement, Dosimetry, and Health Effects - page 18

Delaying dissolution has been used as a strategy for controlling drug delivery by increasing lung
retention time. 184,185 However, there may be some concerns about the safety of such an approach. 181
Another approach is to make inhalable hydrogel particles that swell to sizes larger than the macro-
phage uptake limit. These particles can then release the drug, allowing longer delivery times than
traditional drug particles. 186
1.5.3 d osiMetry
Dosimetry is generally linked to the physicochemical properties of a drug; however, other fac-
tors that may inluence the decision to formulate or administer a drug by a determined device
or devices are technological implications, the health condition of the patient, target site in the
airways, and the therapeutic dose. Doses are drug speciic and they are inluenced by the potency
of the drug itself. In addition, the throughput of a device and the RF need to be considered.
Throughput is used to describe the amount of drug deliverable from an aerosol device, while RF
describes the fraction of aerosolized dose surviving iltration and impaction mechanisms of the
nasopharynx. 187
Although it was generally believed that dosimetry from MDIs was more eficient, convenient,
and reproducible than DPIs and nebulizers, emerging technologies have changed this perspective.
Gamma scintigraphy and pharmacokinetic (charcoal-block) methods have been used to quantify the
amount and pattern of deposition in human lungs. 188-190 The inluence of pulmonary physiology and
pressure gradients on the dosimetry of inhaler devices has been studied. 191,192 Martonen et al. have
developed models to study human lung dosimetry and deposition. 193 These models can simulate
effects of aerosol polydispersity and hygroscopicity, lung morphology, and patient ventilation, age,
and airway disease. Another model of mechanistic dosimetry developed by Lazardis et al. describes
the dynamics of respirable particles. Model predictions of deposition and transport of aerosols are
based on equations that describe changes in particle size and mass distribution as a consequence of
nucleation, condensation, coagulation, and deposition processes.
1.5.3.1 Bolus Delivery
Table 1.5 shows some common drugs administered by inhalation device, the doses dispensed with
each inhalation, and the therapeutic doses required per day. 194 In general, DPIs and MDIs are used
for single delivery of medications on a single breath; doses range from 4 to 500 μg and require
administration two to six times a day. MDIs are capable of delivering very accurate and reproduc-
ible doses. The valves in the device can deliver volumes of the formulation between 25 and 100 μL.
Characteristics that can inluence the amount of drug to be formulated and, therefore, the amount of
drug that can be dosed are drug characteristics such as solubility and concentration, and the addi-
tion of excipients such as surfactants (to minimize particle aggregation which improves physical
stability and dose uniformity), solvents (to aid in drug solubility, carrier properties), and propellants.
The use of accessories such as spacers with MDIs improves inhalant technique and drug delivery. 16
Some factors that inluence the size of doses delivered by DPIs are drug characteristics, the method
used to produce ine particles, blend uniformity, and factors related to the device itself such as ine
particle fraction and emitted dose of the formulation.
1.5.3.2 Continuous Delivery
As mentioned in previous sections, the use of nebulizers is preferred in hospital settings, acute con-
ditions, and treatments in elderly patients and children. This is mainly because required doses of the
prescribed drug are very large and have to be administered over long periods of time or because the
health condition of the patient has limited his/her ability to breath adequately to use other inhala-
tion device. In most cases, once the clinical condition of an adult patient improves, the prescribed