XU Haoyuan¹，REN Manhua¹，HE Xianhong¹，CHEN Lei²，ZHANG Xin¹，GUAN jian¹，MAO Shirui¹

1. School of Pharmacy， Shenyang Pharmaceutical University， Shenyang 110016， China；2. Chinese Pharmacopoeia Commission，Beijing 100061，China

Abstract

Significance Continuous manufacturing is the future trend in tablet manufacturing. In order to accelerate the development of continuous tablet manufacturing， this article analyzes the influence of powder properties of pharmaceutical ingredients on continuous manufacturing. An in-depth understanding of powder properties enhances tablet quality， as well as the efficiency and homogeneity of continuous tablet manufacturing.

Progress So far， three main methods of continuous tablet manufacturing have improved production capability： continuous direct compression， continuous wet granulation， and continuous dry granulation. Among these， due to the limited number of unit operations involved， continuous direct compression has become the most popular method of continuous tablet manufacturing. Compared to batch manufacturing， continuous tablet manufacturing integrates unit operations， including loss-in-weight feeders，continuous mixers， continuous tablet press， roller compactor， twin-screw granulation （TSG）， and fluidized bed drying. The powder properties of pharmaceutical ingredients play a pivotal role in these unit operations， affecting flow behavior and tablet quality. During the continuous direct compression process， the physical properties of the powder， such as density， particle size，and particle shape， affect the flowability of powders， which in turn impacts feedability， mixing uniformity， and hence the drug content of the final tablet. Flowability can be characterized by emerging technologies such as shear testing or traditional static tests， such as the angle of repose and Carr's index. The compression mechanism of the material， such as brittle or plastic deformation， moisture content， and crystal habit， affects the compressibility and compactibility of the material. Powders with good compressibility and compactibility can be used to obtain tablets with a smooth appearance and sufficient hardness through appropriate process parameters. Compressibility and compactability can be evaluated using mathematical equations such as Heckel's equation， Shapiro's equation， Ryshkewitch-Duckworth's equation， and others. Continuous dry granulation is suitable for moisture- and heat-sensitive materials， and the effect of roller compactor process parameters on ribbon density and particle size needs to be emphasized. In addition， the process may lead to loss of tabletability. Continuous TSG has great potential due to its high efficiency， flexibility， and improved tabletability of granules. The properties of the binder and process parameters， such as screw speed and liquid-solid ratio， affect the particle size of the granules， as well as tablet porosity， disintegration time， and hardness. TSG is always integrated with a fluidized bed dryer， resulting in a controlled and homogeneous drying process， which greatly improves product quality and production efficiency. Process analytical technology （PAT） is a key technology for continuous manufacturing， including near-infrared spectroscopy， Raman spectroscopy， microwave resonance， focused beam reflectivity measurement， and other technologies. With PAT tools， the critical quality attributes of powders and tablets in each unit operation， such as drug content， moisture content， particle size， and other properties， can be monitored in real time.

陈蕾（1975—），女，主任药师，硕士，研究方向为药用辅料和药包材标准管理。E-mail：chenlei@chp. org. cn。