Complex formulation strategies to overcome the delivery hurdles of lapatinib in metastatic breast cancer

Breast cancer (BC) is the most prevalent cause of death in women due to cancer worldwide. In 2020, globally, almost 3 million new cases of BC were recognized out of which approximately 684,900 BC-associated deaths were reported due to consequences of metastatic BC (MBC). For its efficient treatment lapatinib (LTN), a dual receptor tyrosine kinase inhibitor (TKI) combination with capecitabine was approved by USFDA. It is a Bio-pharmaceutical Classification System (BCS) class II drug with water solubility of (0.0223 mg/mL) and exhibits a positive food effect (2.67-4.25-fold). The lower aqueous solubility of LTN restricts its dissolution in a gastro-intestinal fluid resulting in variable absorption and poor bioavailability. Furthermore, 99% of LTN binds to plasma proteins resulting in minimal accessibility of free LTN at the cancer site. Hence, a large daily dose of LTN is required to be prescribed. The patent expiry on the innovated product in 2021 has fuelled up the need to develop complex delivery system to overcome the biopharmaceutical hurdles of the drug. The present review critically analyses the various intrinsic fundamental properties of drug molecule that should be taken into consideration while designing a complex delivery system for LTN and the such several formulation approaches reported in literature so far to enhance the pharmacokinetic and pharmacodynamic properties of LTN. This review also discusses the various combinational approaches reported with LTN to overcome the hurdles related to the drug. It also covers various recent ongoing clinical trials on LTN and to provide new perspectives for the development of complex formulations.