Lactose in tablets: functionality, critical material attributes, applications, modifications and co-processed excipients

Abstract

Lactose is one of the most widespread excipients used in the pharmaceutical industry. Because of its water solubility and acceptable flowability, lactose is generally added into tablet formulation to improve wettability and undesirable flowability. Based on quality by design, a better understanding of the critical material attributes (CMAs) of raw materials is beneficial in guiding the improvement of tablet quality and the development of lactose. Additionally, the modifications and co-processing of lactose can introduce more-desirable characteristics to the resulting particles. This review focuses on the functionality, CMAs, applications, modifications and co-processing of lactose in tablets.

Introduction

Lactose application spans the dairy, food and pharmaceutical industries. Lactose is added as an ingredient to infant formula, pharmaceuticals and animal feed.¹ Additionally, lactose and lactose-based co-processed excipients (CPEs) are extensively used in the pharmaceutical industry, particularly as excipients in tablets. Approximately 60–70% of pharmaceutical preparations contain lactose, and this is one of the highest usage rates in pharmaceutical excipients.² There is no doubt that tablets are one of the most vital components in oral solid dosage forms, mainly including direct compression (DC), wet granulation tableting and dry granulation tableting.

Based on the quality by design (QbD) concept, the critical material attributes (CMAs) of excipients largely determine the critical quality attributes (CQAs). The properties of excipients belong to one of the elements of QbD.³ Therefore, it is essential to understand the link between CMAs and CQAs. With the development of the pharmaceutical industry, the requirements for excipient properties are increasing. Although the brittleness of lactose can cause negative effects on product quality, the developments of lactose and its CPEs are not limited by this disadvantage. To compensate for the lack of lactose, modifications and co-processing methods are used to change the physical properties, thus making production easier and improving tableting performance.⁴

Although a book was published on the evolutionary role, health effects and applications of lactose in 2019, it only briefly described the functionality-related characteristics of lactose in tablet preparation and the testing methods of relevant attributes.² Another paper focusing on the source, production and application of lactose was published in 2022.⁵ In this review, we systematically discuss the correlations between tablet quality and material attributes of lactose based on the QbD concept. Meanwhile, the development and advances in the modification of lactose and co-processing with excipients or active pharmaceutical ingredients (APIs) are summarized. These systematic summaries have not been mentioned in previous literature. Subsequently, the functions and applications of lactose in various types of tablets are present. In this way, this review aims to provide a guide for further research and development on lactose.