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

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
• mucociliary escalator
• sustained release formulations
• drug complexes
• site-specific delivery
• polymer-drug conjugates
• drug-polymer matrix
• nano-system
• chemical modification of drugs

Article highlights

• Inhaled modified release technology offers excellent benefits over the conventional pulmonary delivery system that, include

  1. Efficient drug deposition in the desired site of the respiratory tract

  2. Site -specific delivery

  3. Extended pulmonary residence time with minimum systemic exposure

  4. Reduced dosing frequency and improved patient compliance.

• Microparticles and nanoparticle-based systems are widely studied for developing modified release inhaled formulations, of which liposomes and PLGA-based microparticles are available for clinical use.

• Clinical translation of this modified release formulation is challenging, perhaps due to multifactorial reasons:

1. Scalability and manufacturability of modified release inhaled formulations

2. Batch-to-batch variability in the characteristics of the formulations

3. Lack of long-term safety data

4. Regulatory hurdles stemming from lack of uniformity in formulation characteristics and drug-device combination products

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study is supported in parts by a fund from NIH 1R01HL144590-01 (to F Ahsan), NIH R42HL151045 (to F Ahsan) and Cardiovascular Medical Research and Education Funds (to F Ahsan). D Saha is supported in part by a fund from the DOD (W81XWH-20-1-0702).