Aprepitant: Review on Solubility Enhancement.

Abstract

Introduction: Substance P and its neurokinin (NK-1) receptors are upregulated in different pathophysiological conditions. Overexpression of the NK-1 receptor in cancer conditions has provided a promising pathway for cancer treatment. Clinically, Aprepitant (APT) is used as the only NK-1 antagonist in chemotherapy-induced nausea and vomiting (CINV). Currently, investigations into using APT as a synergistic combination with radiation or standard chemotherapeutic drugs are underway. However, APT is categorised as a BCS Class IV drug, and therefore, solubility is one of the challenges when it must be delivered parenterally. The present review aims to understand the solubility enhancement techniques for better bioavailability.

Methodology: Research and review articles were sought to understand the chemistry and solubility enhancement techniques reported for APT. Search engines such as Science Direct, PubMed, Bentham, and Google Scholar were used with the keywords "Aprepitant, solubility, NK1 receptor, parenteral dosage form."

Result: The review comprehensively discusses the methods to improve the solubility of APT using innovative technologies, including nanotechnology.

Discussion: The review highlights the challenges in the utilisation of APT as a treatment for CINV and a promising anticancer drug. Various solubility enhancement techniques can be used for oral administration of APT; however, for parenteral dosage forms, appropriate use of excipients and stability are essential for its safe clinical use.

Conclusion: The available solubility enhancement techniques discussed come with benefits and limitations. Fosaprepitant, a prodrug, is preferably used as an IV dosage form. Similarly, modification to a prodrug and solubility-enhancing excipients for nanoformulation can help make APT a promising therapy.