Abstract
It is well established that currently available inhaled drug formulations are associated with extremely low lung deposition. Currently available technologies alleviate this low deposition problem via mixing the drug with inert larger particles, such as lactose monohydrate. Those inert particles are retained in the inhalation device or impacted in the throat and swallowed, allowing the smaller drug particles to continue their journey towards the lungs. While this seems like a practical approach, in some formulations, the ratio between the carrier to drug particles can be as much as 30 to 1. This limitation becomes more critical when treating lung conditions that inherently require large doses of the drug, such as antibiotics and antivirals that treat lung infections and anticancer drugs. The focus of this review article is to review the recent advancements in carrier free technologies that are based on coamorphous solid dispersions and cocrystals that can improve flow properties, and help with delivering larger doses of the drug to the lungs.
Highlights
Anticancer Drugs Using SolidThe respiratory tract is susceptible to a range of conditions, such as viral, bacterial and fungal infections [1], which in turn can result in an exacerbation of other existing conditions through inflammation [2]
One study found that for Pseudomonas aeruginosa biofilms in cystic fibrosis patients, the majority of the bacteria were present in the conducting zone, which acted as a reservoir for the bacteria to multiply and form biofilms [45]
One study compared two suspensions of beclomethasone dipropionate labelled with technetium-99 in a metered-dose inhaler, by which the first formulation was dissolved in hydrofluoroalkane, and the other was dissolved in chlorofluorocarbon [63], it demonstrated that the different preparation methods led to a difference in both mass median aerodynamic diameter (MMAD) and lung deposition
Summary
The respiratory tract is susceptible to a range of conditions, such as viral, bacterial and fungal infections [1], which in turn can result in an exacerbation of other existing conditions through inflammation [2]. Current technologies are based on formulating the required doses of the active pharmaceutical ingredient (API) with the addition of excipients (known as carrier particles) [10] These carrier particles serve to minimise undesired deposition into the oropharyngeal region, as well as reducing loss in the inhalation device itself. Among approaches to deliver larger doses of the drug to the lungs is solid dispersions. The process is influenced by Brownian motion—in other words, motion increases with decreasing particle size and particles move from a higher concentration to a lower concentration leading to the deposition upon contact with the airway walls This mechanism heavily influences deposition in the lower regions of the lungs and the alveoli.
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