Pulmonary Formulations: What Remains to be Done?

Abstract

Significant advances have been made in the last 50 years in developing safe and efficacious aerosol formulations for pulmonary delivery. The key to future innovation may lie at the interface between biology and particle engineering. Improved understanding of biological processes including particle clearance, cellular targeting, intracellular trafficking, and drug absorption are needed to better design formulations that deliver to the "target" with the optimal balance of pharmacodynamic, pharmacokinetic, and safety profiles. More specifically, continued advances are needed in the development of: (1) controlled release formulations; (2) formulations with improved regional targeting within the lungs (e.g., airway versus alveoli and vice versa); (3) formulations containing active targeting moieties; (4) formulation strategies for improving the systemic bioavailability of inhaled macromolecules; (5) formulation strategies for delivering macromolecules, including siRNA and DNA into cells; and (f) formulations with improved dose consistency. It is likely that such innovation will require the development of novel excipients and particle engineering strategies. Future innovation must also take into the account the changing marketplace and the diverse set of customers (patient, healthcare professional, heath authorities, payers, and politicians) who must be satisfied. The pharmacoeconomics of new delivery systems will be closely scrutinized, so it is imperative that cost factors be taken into account. Otherwise, the new technology option may overshoot the evolving inhalation marketplace.

Advancements in Dry Powder Inhaler

“…The drug is dissolved in a solvent and then precipitated to produce fine particles [25,26]. This technique allows for greater control of particle properties like morphology, porosity, density, particle size and distribution, which further govern powder properties such as powder flow and dispersibility [27]. Dispersible powders with improved aerodynamic properties have been achieved without the addition of carrier particles; the powder properties are improved.…”

“…High drug loadings about 90-95% w/w are possible [25]. Improvements in lung delivery can be achieved by spray dried, low density and highly porous particles which decrease interparticle cohesive forces [27]. The PulmoSpheres delivery is independent of the patient's inspiratory flow rate, reducing dosing variability.…”

Drug-Resistant Tuberculosis: Recent Approach in Polymer Based Nanomedicine

“…The nanosystem containing ATDs have shown desirable results in the animal models for the treatment of TB [68]. However, precise targeting in the lungs still being unmet due to the regional uptake of drugs in the airways with the alveolar region [69]. Still the possibility of dosing the nanosystem containing ATDs weekly or fortnightly have been a key of interest in the nanotechnological research for the TB.…”

Engineered PLGA nano- and micro-carriers for pulmonary delivery: challenges and promises

“…If in the past inhaling 'vapours' (Egyptians in 1500) or smoking cigarettes (Potter's cigarettes in 1802) was sufficient, with the rapidly growing popularity and sophistication of therapies, there is an increasing demand for tailor-made inhalable drug formulations able to yield the best therapeutic outcomes via the most efficient delivery to the lungs. [1] It is well established that key features of the formulation (e.g., aerodynamic size, flow and aerosolization properties) will affect the likelihood of it being deposited in the desired region of the lung. [2] In the case of inhaled drugs required for the treatment of lung diseases, such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), an effective 'local' delivery (i.e.…”

“…[1,8] As a matter of fact, DDS may offer substantial advantages over conventional dosage forms for inhalation, including long-term maintenance of drug concentrations within a desired therapeutic range, reduced doses, reduced dosing frequency, the potential for limited side effects and, last but not least, improved patient adherence to the therapy. This would represent a real benefit for those patients suffering from chronic lung diseases.…”