Nanocrystals for controlled delivery: state of the art and approved drug products

ABSTRACT

Introduction

Controlled/extended-release formulations offer numerous benefits over conventional especially reduced side effects, improved therapeutic outcomes, and high patient compliance. Controlled release nanocrystal is extremely versatile technology with several advantages such as very high drug loading, ease of manufacturing, avoidance of dose dumping, reproducible drug release. Usually, nanonization of drug is performed to improve dissolution rate, intrinsic solubility, and thereby bioavailability. Most of the times, this is done for immediate release dosage forms where objective is quick onset of action. However, nanocrystals can also provide a sustained, reproducible plasma concentration profile for weeks to months based on tissue microenvironment, surface coating and administration route.

Areas covered

This review briefly describes the methods for producing nanocrystals, summarizes preclinical research and commercial products demonstrating tremendous potential of controlled release nanocrystals.

Expert opinion

Lipophilic drugs are attractive candidates for the development of nanocrystal based controlled release formulations. However, constraint should be practiced while generalizing the technology for the controlled release purpose. Not all drugs fit in the requirement from the perspectives of physicochemical properties or pharmacokinetics. Additionally, technologies should be explored which can convert the nanocrystal into its final dosage form for administration yet preserves the benefits of small particle size and controlled release.

KEYWORDS:

• Nanocrystals
• nanosuspension
• controlled release
• extended release
• size reduction

Article highlights

• Nanocrystals can provide a sustained, reproducible plasma concentration profile for weeks to months.

• This review summarizes preclinical research and commercial products in the market based on controlled release nanocrystals.

• Nanocrystals on their own cause rapid release of an active suggesting the limitations of technology to develop controlled release formulations.

• However, nanocrystals incorporated into other drug delivery systems such as polymeric microparticles can provide sustained drug release via various routes.

• In clinics, nanocrystal-based technologies for controlled release is most successful for parenteral route.

• Future research should be focused on developing controlled release nanocrystals of both hydrophilic and lipophilic drugs.

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 paper was not funded.