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Review
. 2023 Mar;20(3):335-348.
doi: 10.1080/17425247.2023.2175814. Epub 2023 Feb 16.

An evolving perspective on novel modified release drug delivery systems for inhalational therapy

Tanvirul Hye  1 , Sakib M Moinuddin  2   3 , Tanoy Sarkar  2   3 , Trieu Nguyen  2   3 , Dipongkor Saha  2 , Fakhrul Ahsan  2   3   4
Affiliations
Review

An evolving perspective on novel modified release drug delivery systems for inhalational therapy

Tanvirul Hye et al. Expert Opin Drug Deliv. 2023 Mar.

Abstract

Introduction: Drugs delivered via the lungs are predominantly used to treat various respiratory disorders, including asthma, chronic obstructive pulmonary diseases, respiratory tract infections and lung cancers, and pulmonary vascular diseases such as pulmonary hypertension. To treat respiratory diseases, targeted, modified or controlled release inhalation formulations are desirable for improved patient compliance and superior therapeutic outcome.

Areas covered: This review summarizes the important factors that have an impact on the inhalable modified release formulation approaches with a focus toward various formulation strategies, including dissolution rate-controlled systems, drug complexes, site-specific delivery, drug-polymer conjugates, and drug-polymer matrix systems, lipid matrix particles, nanosystems, and formulations that can bypass clearance via mucociliary system and alveolar macrophages.

Expert opinion: Inhaled modified release formulations can potentially reduce dosing frequency by extending drug's residence time in the lungs. However, inhalable modified or controlled release drug delivery systems remain unexplored and underdeveloped from the commercialization perspective. This review paper addresses the current state-of-the-art of inhaled controlled release formulations, elaborates on the avenues for developing newer technologies for formulating various drugs with tailored release profiles after inhalational delivery and explains the challenges associated with translational feasibility of modified release inhalable formulations.

Keywords: Control release; chemical modification of drugs; drug complexes; drug-polymer matrix; mucociliary escalator; nano-system; polymer-drug conjugates; site-specific delivery; sustained release formulations.

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Conflict of interest statement

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Pulmonary drug delivery barriers. Pulmonary clearance by mucociliary escalator, phagocytosis, target site binding, and systemic absorption depends on an interplay between multiple factors.
Figure 2.
Figure 2.
Structural comparison of SABA (salbutamol) and LABA (salmeterol and formoterol). Both groups have N- substituted lipophilic groups and one or more chiral centers (*). The SABA is less lipophilic owing to the shorter alkyl chain. LABAs are more lipophilic due to a longer lipophilic tail, which helps a longer duration of action.
Figure 3.
Figure 3.
Lung activation of ciclesonide after inhalation. The local esterase enzyme cleaves the ester group and releases the free active drug.
Figure 4.
Figure 4.
Schematic illustration of phagocytosis of liposome by macrophages. During the endocytosis process, macrophages take up the intact vesicle. Drugs are released from the carriers following the degradation of the carrier.
Figure 5.
Figure 5.
Comparative features of lung deposition pattern in mucoadhesive particles vs. mucus penetrating particles.
Figure 6.
Figure 6.
Tobramycin dry powder formulation for inhalation. The power is made of fine porous particles (dae <5 ?m), which provides several benefits such as reduced aggregation, better flowability, and efficient airways and peripheral lungs distribution.
See this image and copyright information in PMC

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