A comprehensive review of the Maillard reaction in solid pharmaceutical dosage forms: a focus on lactose

INTRODUCTION: Solid dosage forms face the risk of the Maillard reaction during development and storage. This reaction occurs between reducing excipients and amino-group-containing drugs, potentially leading to discoloration, impurity formation, and degradation of active ingredients, significantly impacting product quality and excipient selection. AREAS COVERED: Using lactose, a representative reducing excipient, as an example, this article systematically explores the mechanisms, influencing factors, control strategies, and potential applications of the Maillard reaction in solid dosage forms. It aims to provide theoretical support and practical guidance for formulation optimization, quality control, and innovative development of pharmaceutical preparations. Searches of Google Scholar and PubMed were undertaken to gather the literature included in this review. EXPERT OPINION: The Maillard reaction between lactose and amino-group-containing drugs poses a significant quality risk, directly affecting the stability and safety of pharmaceutical preparations. In generic drug development, controlling this reaction is a critical step in achieving consistency with the reference listed drug (RLD). Instead of simply avoiding lactose, a proactive strategy should be adopted early in development. Through compatibility assessment, mechanistic studies, and comprehensive control measures, this challenge can be transformed into an opportunity for formulation optimization and innovation, thereby advancing the development of high-quality solid dosage forms.