Recent advances in the development of asenapine formulations

ABSTRACT

Introduction

Asenapine maleate (AM) is an atypical antipsychotic agent, that has been widely prescribed for the management of schizoaffective disorders. However, the bioavailability of AM is extremely poor due to the extensive first-pass metabolism. With the advancement in pharmaceutical technologies, significant strides have been made to create novel formulations to address the bioavailability problem of AM.

Areas covered

This review article provides an insight into all the formulation approaches undertaken by researchers to increase the bioavailability of AM encompassing the works utilizing ultrasound mediated transdermal delivery, nose to brain delivery, intestinal lymphatic system targeting, in situ implants, etc. All the patents associated with AM formulation have also been discussed and summarized.

Expert opinion

Numerous studies have been carried out on AM formulations over the recent years, many of these studies have shown significant improvement in bioavailability. We have also mentioned the unexplored domains which can be exploited for further enhancing the bioavailability of AM. Nonetheless, most of these studies are still limited to the research laboratory level and face multiple hurdles before making into the market. Attaining controllability and reproducibility for the production of novel formulations is needed to enable its transition from bench to bedside.

KEYWORDS:

• Asenapine maleate
• bioavailability
• drug delivery systems
• liposome
• nanoparticle
• targeting
• lipid-based systems

Article highlights

• Asenapine maleate currently, is an essential antipsychotic agent in the management of schizoaffective disorders. Nonetheless, its full potential is restricted due to poor bioavailability caused by the first-pass metabolism.

• Various drug delivery approaches such as delivery to the brain via the nasal route, bypassing the first-pass metabolism via intestinal lymphatic route, rapidly disintegrating sublingual films, in situ implants, inclusion complexes, self-emulsifying drug delivery systems, liposomes, nanoparticles are being explored by researchers.

• Nano-carrier based drug delivery system approaches such as solid lipid nanoparticles, nanostructured lipid carriers, liposomes, nanoemulsions, nanotransferosomes, etc. are being currently explored.

• The nature of lipid formulations to form chylomicrons can be used to gain access into the intestinal lymphatic system thereby avoiding first-pass metabolism.

• Modifying the surface of drug carrier systems with TPGS or RGD helps the system to cross biological barriers, effectively improving the chances of an extended retention of drug in the body

• Mechanical energy in the form of ultrasound can be used to mediate the enhancement of transdermal drug delivery. Ultrasound can change the arrangement of stratum corneum, loosening it, and facilitating drug penetration.

• Extensive vasculature, large surface area, and proximity to the brain are the key features of the nasal cavity which can be used in AM delivery to the brain for treating CNS disorders.

This box summarizes key points contained in the article.

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

Authors are thankful to the Science and Engineering Research Board, Dept. of Science and Technology, New Delhi, India (Ref. No. EMR/2016/007006) for the research funding and Manipal Academy of Higher Eduction for the Dr TMA Pai PhD Scholarship