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Continuous Wet Granulation

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Continuous Pharmaceutical Processing

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 42))

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Abstract

Wet granulation is a critical unit operation in solid dosage form manufacturing in the pharmaceutical industry. Traditionally, wet granulation has been a batch process. Recently, there has been a move toward more advanced manufacturing approaches such as continuous processing to allow more rigorous process control, consistent quality assurance, and reduced capital costs. This chapter discusses continuous wet granulation process with emphasis on twin screw granulation as the most commonly used continuous granulation approach in the pharmaceutical industry. The key design features of a twin screw granulator (TSG) are described, and comparisons with batch high shear granulation equipment are made. The effects of formulation and process variables on granule attributes are discussed. Mechanistic studies of screw elements with the proposed granulation rate processes are presented. Real-time process monitoring tools, including spectroscopic and imaging techniques, are described. Implementation of dimensional analysis as a tool for scaling up/scaling out of continuous twin screw granulation is presented. Two numerical methods, that is, population balance model (PBM) and discrete element method (DEM), are chosen for the multiscale modeling of twin screw granulation, and their coupling mechanisms of data exchange between DEM and PBM are discussed.

The opinions and conclusions expressed in this chapter are solely the views of the authors and do not necessarily reflect those of the Food and Drug Administration.

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Abbreviations

a :

Particle radius, mm

b M :

Breakage function

B(v, t):

Birth rate, m−3 s−1

B agg :

Birth rate of agglomeration, m−3 s−1

B break :

Birth rate of breakage, m−3 s−1

B nuc :

Birth rate of nucleation, m−3 s−1

C impact :

Impact frequency, s−1

d p :

Particle diameter, mm

D :

Barrel diameter, mm

D(v, t):

Death rate, m−3 s−1

D break :

Death rate of breakage, m−3 s−1

\( {D}_{m_p,\kern0.28em \mathrm{nuc}} \) :

Death rate of powder particles, kg m−3 s−1

d 50 :

Median size of feed particle, mm

F n :

Series of geometric ratios

\( {F}_{\mathrm{powder}}^{\mathrm{in}} \) :

Flow rate of additional powder stream, kgs−1

G :

Growth rate, s−1

G m :

Maximum growth rate, s−1

G shear :

Shear rate, s−1

h :

Interparticle gap, mm

k :

Compaction rate constant, s−1

l :

Liquid volume, m3

L :

Barrel length, mm

\( {\dot{L}}_{\mathrm{in},\mathrm{powder}}\left(x,t\right) \) :

Rate of liquid addition to the fine powder, kgh−1

m :

Mass of particle, kg

M powder :

Mass of fine powder, kg

M granule :

Mass of granule, kg

\( {\dot{m}}_p \) :

Mass flow rate of powder, kg/h

\( {\dot{m}}_l \) :

Mass flow rate of liquid, kg/h

n :

Population density of length function, m−3

P 1 :

Rate coefficient

P 2 :

Size-dependent exponent

St v :

Stokes deformation number

V droplet :

Volume of a single liquid droplet, m3

V nuc :

Volume of particle in saturated granule, m3

V L, nuc :

Volume of liquid in saturated granule, m3

V p :

Per-particle pore volume, m3

S 1 :

Volume of solid component 1, m3

S 2 :

Volume of solid component 2, m3

SM(w, v):

Specific breakage rate, s−1

x w :

Moisture content of powder

x wc :

Critical moisture content of powder

∆x :

Reduction of particle size

σ:

Standard deviation

ω :

Angular velocity of the shaft, rads−1

ε :

Granule porosity

ε bed :

Powder bed porosity

εmin:

Minimum granule porosity

ρ b :

Particle density, kg m−3

u 0 :

Collision velocity, ms−1

μ :

Binder viscosity

LSR:

Liquid/solid ratio

PFN:

Powder feed number

Fr:

Froude number

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Authors and Affiliations

  1. Office of Pharmaceutical Manufacturing Assessment, Office of Pharmaceutical Quality, CDER, FDA, Silver Spring, MD, USA

    Arwa El Hagrasy

  2. Chemical and Biological Engineering, University of Sheffield, Sheffield, UK

    Li Ge Wang & Jim Litster

Authors
  1. Arwa El Hagrasy
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  2. Li Ge Wang
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  3. Jim Litster
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Corresponding author

Correspondence to Jim Litster .

Editor information

Editors and Affiliations

  1. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA

    Zoltan K Nagy

  2. Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Arwa El Hagrasy

  3. Department of Chemical and Biochemical Engineering, The University of Sheffield, Sheffield, UK

    Jim Litster

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El Hagrasy, A., Wang, L.G., Litster, J. (2020). Continuous Wet Granulation. In: Nagy, Z., El Hagrasy, A., Litster, J. (eds) Continuous Pharmaceutical Processing. AAPS Advances in the Pharmaceutical Sciences Series, vol 42. Springer, Cham. https://doi.org/10.1007/978-3-030-41524-2_8

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