Critical pharmaceutical process identification considering chemical composition, biological activity, and batch-to-batch consistency: A case study of notoginseng total saponins

Objective: Critical pharmaceutical process identification(CPPI) is an important step in the implementation of quality by design concept to traditional Chinese medicines(TCMs). Risk assessment methods are usually used in CPPI. However, risk evaluation is usually subjective. The purpose of this work is to present a more objective CPPI method.Methods: A CPPI method considering chemical composition, biological activity, and batch-to-batch consistency was presented in this work. The manufacturing process of notoginseng total saponins(NTS) was investigated as an example. The changes of chemical composition, biological activity, and chemical composition consistency after main processes were measured and compared. A significant change of them indicated a critical process.Results: After extraction process and chromatography process, saponin purity and chemical composition similarity remarkably increased, and saponin content variations decreased. Thrombin inhibitory activity was remarkably decreased after chromatography process. Because of the large influences on NTS quality,extraction process and chromatography process were identified to be critical processes of NTS.Conclusion: Based on a comprehensive and objective examination of the role of each process, critical pharmaceutical processes can be identified. A similar method can also be applied to other TCM processes.

An asymmetric non-fused electron-deficient building block for low-cost polymer acceptor in all-polymer solar cells

The development of polymerized fused-ring small molecule acceptors(FRA-PAs) has boosted the performance of all-polymer solar cells(all-PSCs).However,these FRA-PAs suffer from lengthy synthesis steps and high production costs due to the high degree of synthetic complexity for fused-ring small molecule acceptors(FRAs).Furthermore,most FRA-PAs exhibit strong batch-to-batch variation,limiting further industrial applications.Herein,we designed and synthesized asymmetric non-fused electron-deficient building block TIC-Br with a simple structure(only three synthetic steps),showing a planar configuration,excellent electron affinity,and large dipole moment.A simple polymer acceptor PTIB was further developed by polymerization of TIC-Br and sensitized fluorinated-thienyl benzodithiophene(BDT-TF-Sn).PTIB exhibits a broad absorption from 300 to 800 nm,a suitable lowest unoccupied molecular orbital(LUMO) energy level of-3.86 e V,and moderate electron mobility(1.02×10^(-4)cm^(2)V^(-1)s^(-1)).When matched with PM6,the device achieved the best PCE of 10.11%with a high V_(OC) of 0.97 V,which is one of the highest among those reported all-PSCs.More importantly,PTIB exhibits a lower synthetic complexity index(SC=35.0%)and higher figure-of-merit values(FOM=29.0%) than all the reported high-performance PAs.The polymer also exhibits excellent batch-to-batch reproducibility and great potential for scale-up fabrication.This study indicates that TIC-Br is a promising building block for constructing low-cost polymer acceptors for large-scale applications in all-PSCs.

An approach to optimize the batch mixing process for improving the quality consistency of the products made from traditional Chinese medicines

The efficacy of traditional Chinese medicine(TCM)is based on the combined effects of its constituents.Variation in chemical composition between batches of TCM has always been the deterring factor in achieving consistency in efficacy.The batch mixing process can significantly reduce the batch-to-batch quality variation in TCM extracts by mixing them in a well-designed proportion.However,reducing the quality variation without sacrificing too much of the production efficiency is one of the challenges.Accordingly,an innovative and practical batch mixing method aimed at providing acceptable efficiency for industrial production of TCM products is proposed in this work,which uses a minimum number of batches of extracts to meet the content limits.The important factors affecting the utilization ratio of the extracts(URE)were studied by simulations.The results have shown that URE was affected by the correlation between the contents of constituents,and URE decreased with the increase in the number of targets and the relative standard deviations of the contents.URE could be increased by increasing the number of storage tanks.The results have provided a reference for designing the batch mixing process.The proposed method has possible application value in reducing the quality variation in TCM and providing acceptable production efficiency simultaneously.

Particle shape characterisation and classification using automated microscopy and shape descriptors in batch manufacture of particulate solids

It is known that size alone, which is often defined as the volume-equivalent diameter, is not sufficient to characterize many particulate products. The shape of crystalline products can be as important as size in many applications, Traditionally, particulate shape is often defined by several simple descriptors such as the maximum length and the aspect ratio. Although these descriptors are intuitive, they result in a loss of information about the original shape. This paper presents a method to use principal component analysis to derive simple latent shape descriptors from microscope images of particulate products made in batch processes, and the use of these descriptors to identify batch-to-batch variations. Data from batch runs of both a laboratory crystalliser and an industrial crystallisation reactor are analysed using the described approach. Qualitative and quantitative comparisons with the use of traditional shape descriptors that have nhwical meanings and Fourier shape descriptors are also made.

Porous-structure engineered spacer for high-throughput and rapidgrowth of high-quality graphene films

Chemical vapor deposition(CVD)in conjunction with batch-to-batch manufacturing process is considered as the most promising technical route for mass-production of high-quality graphene films.To improve the space utilization of the CVD chamber and increase the throughput per batch,stacking of the Cu foil substrates is efficient,but suffers from the problems of adjacent fusion and the poor mass-transfer.Here,we demonstrate an efficient strategy for high-throughput and rapid growth of high-quality graphene by alternate stacking of Cu foils and porous carbon fiber paper(CFP).Relying on the unhindered mass-transfer through the pores of CFPs,full-covered high-quality graphene films on compact-stacked Cu foils were achieved within 2 min.Computational fluid dynamics(CFD)simulation and isotope labeling technique were performed to explore the gas diffusion and graphene growth process in the confined space of the Cu-CFP stacks.This work provides a feasible method for industrial production of graphene films,which may also be used for batch production of other two-dimensional materials.