(568a) Cephalexin and Amoxicillin Crystal Shape Modification By Manipulating the Supersaturation and Wet Milling
In the present work, we examine the impact of wet milling on the crystal shape, aspect ratio, and size distribution in cephalexin and amoxicillin crystallization processes. Wet milling is commonly used to reduce the crystal size in different processes and to tighten the size distribution. Our results suggest that wet milling not only reduces the mean size of cephalexin monohydrate crystals, but it also leads to further improvements in crystal aspect ratio during the enzymatic synthesis and crystallization process. Based on a systematic study of different milling parameters, we will discuss the impact of milling on crystals of both cephalexin and amoxicillin. Furthermore, we investigate potential improvements in the aspect ratio of the final crystals by combining the milling with a series of pH manipulation steps where small, needle-like crystals are dissolved by periodically increasing the system pH (leading to higher solubility), giving a way to produce larger crystals with improved aspect ratios (Figs. 1A and 1B). The impact of the improved aspect ratio on the filtration rate of both crystals will also be discussed (Fig. 1C).
Fig. 1. Example of improvement in the aspect ratio of cephalexin monohydrate crystals by applying a series of pH swings (A), or periodic milling (B). Both cases lead to the formation of more platelike crystals compared to initially needle-like crystals. Example of the impact of aspect ratio (or size) on filtration rate (C).
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