A Review on Biopharmaceutical, Analytical, and Formulation Aspects of Elagolix

Review Article

Abstract

Elagolix, a first-in-class, orally active, non-peptide gonadotropin-releasing hormone (GnRH) antagonist transformed the treatment for endometriosis and uterine fibroids. Unlike traditional peptide-based GnRH agonists that require parenteral administration and induce initial hormonal flares, elagolix offers dose-dependent estrogen suppression with rapid reversibility. This review analyzes the pharmaceutical and biopharmaceutical attributes that facilitate the oral delivery of this peptide-mimetic small molecule. This work provides the physicochemical profile of elagolix sodium, highlighting its classification as a Biopharmaceutics Classification System (BCS) Class II compound and the implications of its pH-dependent solubility on formulation strategies. Furthermore, the absorption, distribution, metabolism, and excretion (ADME) characteristics are detailed, elucidating the role of hepatic transporters and metabolic enzymes in its pharmacokinetic behavior. The review emphasizes recent advancements in analytical methodologies, including high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), developed for the rigorous quantification of elagolix and its degradation products in complex matrices. Additionally, the implementation of Quality by Design (QbD) principles in optimizing formulation parameters and ensuring critical quality attributes is synthesized. This review explains the pivotal role of elagolix as a model for overcoming the barriers associated with the oral delivery of therapeutics targeting the GnRH receptor by integrating data on stability, solubility enhancement techniques, and regulatory considerations