Understanding effect of filtration and washing on dried product: Paracetamol case study

Abstract

One of the key challenges that the pharmaceutical industry is trying to address is to maintain particle properties across the entire purification and isolation process. This research focuses on the effect of slurry properties, wash solvent, filtration and washing mechanisms on API agglomeration/granulation during the processes of downstream isolation and the impact on the physical properties of the product. In this investigation, each isolation step was analysed to identify factors that have the potential to affect the final product qualities using a multivariate statistical design of experiments approach.The factors which were most detrimental in increasing particle agglomeration, were found to be the particle size of the input material, the quantity and identity of wash solvent and the drying mode. Low boiling point aliphatic

Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development

“…However, there are other factors that can influence agglomeration in this case, for example, the effectiveness of the mechanical removal of the solvent within the first few seconds of drying, 6 as well as cake compaction which can assist with binding particles together. 20 , 21 …”

“…It is thought that if a section of the cake becomes compacted, the majority of the flow of the drying gas will bypass this compacted area, reducing drying performance in this region, which can result in large agglomerates being formed. 20 , 21 …”

“…However, there are other factors that can influence agglomeration in this case, for example, the effectiveness of the mechanical removal of the solvent within the first few seconds of drying, 6 as well as cake compaction which can assist with binding particles together. 20,21 The lowest extent of agglomeration displayed in Table 4 is for a 20 mm cake height, with an inlet pressure and temperature of 2 bar(g) and 45 °C, respectively. It is interesting that this is also the experiment with the lowest mass of solvent after the first 30 s. Table 3 shows that increasing the inlet pressure results in a lower mass of saturated solution left within the cake after the first 30 s of drying.…”

“…It is thought that if a section of the cake becomes compacted, the majority of the flow of the drying gas will bypass this compacted area, reducing drying performance in this region, which can result in large agglomerates being formed. 20,21 These observations suggest that for a system where positive pressure is applied above the cake (controlled by a pressure regulator on the inlet of the system) and vacuum is applied beneath the cake, an optimum inlet pressure is required to achieve the best drying performance in terms of preventing agglomeration. The results displayed in Table 4 suggest that using an inlet pressure of 1 bar(g) can considerably reduce agglomeration, even when processing larger cake heights.…”

A Novel Integrated Workflow for Isolation Solvent Selection Using Prediction and Modeling

“… Viscosity: the viscosity of mother liquor and wash solvent should be similar to promote good displacement washing. 31 , 43 Thermodynamic properties (boiling point, T b , enthalpy of vaporization, Δ H vap , and vapor pressure, V p ): the wash solvent selected should have a low boiling point and enthalpy of vaporization and high vapor pressure to favor the drying process reducing the constant and falling rate drying period; 43 , 44 therefore, reducing the ultimate LOD. If the boiling point of the wash solvent is similar to that of the crystallization solvent, there is a risk of particle agglomeration even if the residual mother liquor quantity at the start of drying is low due to enrichment of the less volatile solvent during drying due to API re-dissolution and subsequent recrystallization leading to interparticle bridge formation.…”