Lean Filtration: Approaches for the Estimation of Cake Properties

Abstract

The majority of active pharmaceutical ingredients (APIs) and intermediates are isolated as solid products through crystallization, filtration, and drying. In some cases, filtration of APIs and intermediates exhibit long cycle times and may potentially become the bottleneck of the entire process train. Thus, early assessment of the cake properties is typically required to evaluate filtration performance prior to scale-up. This work presents two approaches to rapidly estimate the specific cake resistance through lab studies. Using the first approach, a first-order approximation of the specific cake resistance is estimated from data collected during a simple Buchner funnel filtration. The second approach provides a more accurate estimate from a more extensive filtration study incorporating dynamic pressure modulation (DPM, a single filtration with ascending pressures), improving the fidelity of filtration predictions. Results from several case studies demonstrate how a workflow combining these two approaches can be appropriately employed to assess the cake properties from laboratory filtrations for predictions of the pilot/manufacturing plant filtration performance.

Crystallization Process Development for the Final Step of the Biocatalytic Synthesis of Islatravir: Comprehensive Crystal Engineering for a Low-Dose Drug

“…The wet-milled crystals had a d 50 of 22 μm . The specific cake resistance estimated from vacuum filtration of the slurry was ∼1 × 10 12 m/kg, which is an unacceptably poor specific cake resistance for factory production . Furthermore, there was substantial breakthrough of fine particles through the filter, requiring undesirable recycle of the fine particles in the mother liquor through the cake.…”

Manufacturing Poly(3,4‐Ethylenedioxythiophene) Electrocatalytic Sheets for Large‐Scale H2O2 Production

“…The cake resistance (α m ) is extracted from the slope of reciprocal of filtration rate (t/V) versus water volume using Darcy's equation. [35,36] Table 1 compares the dewatering time and specific cake resistance (α m ) calculated using constant pressure modeling of PEDOT 1M (PH1000 treated with 1 m H 2 SO 4 ) films in steps: 0 mg CF, 11 mg CF, 20.5 mg CF, 50 mg CF, 50 mg pulp, 50 mg G-CF1 (no sizing treatment), and 50 mg G-CF2 (epoxy sizing treatment to improve wettability) using constant pressure modeling. Figure 3a clearly demonstrates that with the right amount of CF/G-CF1, the overall filtration performance could be enhanced.…”

A Virtual Plant for Integrated Continuous Manufacturing of a Carfilzomib Drug Substance Intermediate, Part 3: Manganese-Catalyzed Asymmetric Epoxidation, Crystallization, and Filtration

“…Two parallel batch filtration units are used to allow for continuous production of the product solution. The filter model is based on modified Darcy’s law (eqs and ): , where m s is the mass of solids, μ is the filtrate viscosity, α is the specific cake resistance (length/mass), A is the filtration area, R m is the medium resistance, t is the filtration time, Δ P is the pressure drop across the cake, m is the mass of the filtrate, C is the mass of solids per unit volume of liquid in the slurry, ρ is the filtrate density, and n is the cake compressibility. This model was modified to account for continuous operation at constant Δ P , as shown in eq : A set of two experiments were designed and executed in which Δ P was varied from 12.6 to 25 psi and the mass of the filtrate over time was recorded, as shown in Figure .…”

“…Two parallel batch filtration units are used to allow for continuous production of the product solution. The filter model is based on modified Darcy's law (eqs 13 and 14): 31,32…”