Granulation techniques and technologies: recent progresses

Granulation techniques and technologies: recent progresses

Srinivasan Shanmugam

Pharm. R&D Institute, Hanmi Pharm. Co., Ltd., Hwasung, Gyeonggi, Korea

Abstract

Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dustfree granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc. together with physical and chemical stability of the drug. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Among currently available technologies, spray drying, roller compaction, high shear mixing, and fluid bed granulation are worth of note. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable. This review focuses on the recent progress in the granulation techniques and technologies such as pneumatic dry granulation, reverse wet granulation, steam granulation, moisture-activated dry granulation, thermal adhesion granulation, freeze granulation, and foamed binder or foam granulation. This review gives an overview of these with a short description about each development along with its significance and limitations.

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Thermal properties of alumina–MWCNTs composites

Thermal properties of alumina–MWCNTs composites

Alumina–multi-wall carbon nanotubes composites were prepared using a new approach. This process comprises functionalization MWCNTs by acid treatment, stabilization of alumina–MWCNT dispersion with subsequent freezing was used, which resulted in formation of granulated powder with homogeneous distribution of MWCNTs. The ceramic composites were prepared by hot pressing and rapid hot pressing at 1550 °C using these granulated powders. Relative densities, microstructural analysis, Raman spectroscopy, heat capacity as well as thermal diffusivity measurements of composite prepared by hot press and rapid hot press has been studied. Our results show that sintering alumina–MWCNT granulated powder by rapid hot press is effective way how to reach nearly fully dense composite up to 12.5 vol.% of MWCNTs. Relative density of alumina–MWCNT composite with 10 vol.% of MWCNTs in case of composite prepared by rapid hot press was 97.3% of theoretical density whereas in case of composite with same content of MWCNTs prepared by hot press relative density was 79.5%. Thermal diffusivity of composite sintered by rapid hot press and hot press decrease with increasing content of MWCNTs and increasing measuring temperature up to 400 °C. Thermal diffusivity of composites prepared by rapid hot press, which have higher density than composite prepared by hot press, is slightly higher. Thermal conductivity of composites prepared by rapid hot press decrease with increasing content of MWCNTs from 27.8 to 16.7 W/m K and in case of composite prepared by hot press from 24.6 to 7.8 W/m K. This is probably due to the phonon scattering of incorporated MWCNTs in alumina matrix and their intrinsic defects.

Keywords

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Freeze Granulation of vanillin flavour

Effect of whey protein isolate and β-cyclodextrin wall systems on stability of microencapsulated vanillin by spray–freeze drying method

Vanillin flavour is highly volatile in nature and due to that application in food incorporation is limited; hence microencapsulation of vanillin is an ideal technique to increase its stability and functionality. In this study, vanillin was microencapsulated for the first time by non-thermal spray–freeze-drying (SFD) technique and its stability was compared with other conventional techniques such as spray drying (SD) and freeze-drying (FD). Different wall materials like β-cyclodextrin (β-cyd), whey protein isolate (WPI) and combinations of these wall materials (β-cyd + WPI) were used to encapsulate vanillin. SFD microencapsulated vanillin with WPI showed spherical shape with numerous fine pores on the surface, which in turn exhibited good rehydration ability. On the other hand, SD powder depicted spherical shape without pores and FD encapsulated powder yielded larger particle sizes with flaky structure. FTIR analysis confirmed that there was no interaction between vanillin and wall materials. Moreover, spray–freeze-dried vanillin + WPI sample exhibited better thermal stability than spray dried and freeze-dried microencapsulated samples.

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Spray freeze drying for dry powder inhalation of nanoparticles

Spray freeze drying for dry powder inhalation of nanoparticles

Formulating nanoparticles for delivery to the deep lung is complex and many techniques fail in terms of nanoparticle stability. Spray freeze drying (SFD) is suggested here for the production of inhalable nanocomposite microcarriers (NCM). Different nanostructures were prepared and characterized including polymeric and lipid nanoparticles. Nanoparticle suspensions were co-sprayed with a suitable cryoprotectant into a cooled, stainless steel spray tower, followed by freeze drying to form a dry powder while equivalent compositions were spray dried (SD) as controls. SFD-NCM possess larger specific surface areas (67–77 m2/g) and lower densities (0.02 g/cm3) than their corresponding SD-NCM. With the exception of NCM of lipid based nanocarriers, SFD produced NCM with a mass median aerodynamic diameter (MMAD) of 3.0 ± 0.5 μm and fine particle fraction (FPF ⩽ 5.2 μm) of 45 ± 1.6% with aerodynamic performances similar to SD-NCM. However, SFD was superior to SD in terms of maintaining the particle size of all the investigated polymeric and lipid nanocarriers following reconstitution (Sf/Si ratio for SFD ≈ 1 versus >1.5 for SD). The SFD into cooled air proved to be an efficient technique to prepare NCM for pulmonary delivery while maintaining the stability of the nanoparticles.

Keywords

  • Spray freeze drying;
  • Spray drying;
  • Pulmonary;
  • Nanoparticles;
  • Dry powder;
  • Inhalation;
  • Nanocomposite microcarriers

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Spray Freeze Granulation of Nano Powders for Die Pressing

Spray Freeze Granulation of Nano Powders for Die Pressing

Jon Binner, Ketharam Annapoorani, Bala Vaidhyanathan

The processing of nanocrystalline yttria doped zirconia powder via dry forming routes has been investigated via the granulation of the powder using spray freeze drying (SFD). Free-flowing and crushable powders suitable for either die or isosatic pressing have been achieved via the combination of SFD with additions of up to 2 vol% of Freon 11; the latter reducing the strength of the granules whilst not affecting the powder flowability into the die. The approach has allowed relic-free green bodies of up to 55% of theoretical density to be produced using pressures as low as 250 MPa.

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Freeze Granulation: towards dry pressed transparent ceramics

Yield stress modelling of doped alumina suspensions for applications in freeze granulation: towards dry pressed transparent ceramics

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Rheology of powder suspensions is a key factor in many processing routes, and better understanding of the parameters that control the rheology improves technical progress by reducing the empirical factors in the formulation of powder slurries. The strict requirements for the production of transparent polycrystalline alumina demand a fundamental understanding of powder handling and processing steps. The use of dopants (Mg, Y, La) has proven useful, but produces noticeable effects on suspension rheology and influences the choice of the processing route. With the prospect of spray granulation of such slurries, the rheological behaviour of doped alumina suspensions was investigated from a fundamental approach taking into account slurry and particle characteristics, and computing the interparticle potentials. This information was then used in a yield stress model which successfully predicted the rheological behaviour of the doped alumina slurries. A strategy for improved slurry formulation is presented.

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Freeze Granulation of Al2O3-ZrO2-MWCNTs nanocomposites

Mechanical and functional properties of Al2O3–ZrO2–MWCNTs nanocomposites

Multi-walled carbon nanotubes (MWCNTs) are often reported as additives improving mechanical and functional properties of ceramic composites. However, despite tremendous efforts in the field in the past 20 years, the results are still inconclusive. This paper studies room temperature properties of the composites with polycrystalline alumina matrix reinforced with 0.5–2 vol.% MWCNTs (composites AC) and zirconia toughened alumina with 5 vol.% of yttria partially stabilised zirconia (3Y-PSZ) containing 0.5–2 vol.% of MWCNTs (composites AZC). Dense composites were prepared through wet mixing of the respective powders with functionalised MWCNTs, followed by freeze granulation, and hot-pressing of granulated powders. Room temperature bending strength, Young’s modulus, indentation fracture toughness, thermal and electrical conductivity of the composites were studied, and related to their composition and microstructure. Slight increase of Young’s modulus, indentation fracture toughness, bending strength, and thermal conductivity was observed at the MWCNTs contents ≤1 vol.%. At higher MWCNTs contents the properties were impaired by agglomeration of the MWCNTs. The DC electrical conductivity increased with increasing volume fraction of the MWCNTs.

Keywords

  • Alumina;
  • Carbon nanotubes;
  • Bending strength;
  • Young’s modulus;
  • Thermal conductivity

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ZST ceramics via freeze granulation

Fostering the properties of Zr0.8Sn0.2TiO4 (ZST) ceramics via freeze granulation without sintering additives

S. M. Olhero,   Ajay Kaushal and   J. M. F. Ferreira

The present paper reports the overall benefits of freeze granulation for enhancing the properties of zirconium tin titanate Zr0.8Sn0.2TiO4 (ZST) ceramics in the total absence of sintering additives. The ZST powder was synthesized by solid state reaction and attrition milled in ethanol for 10 h. This starting non-granulated powder (NG-ZST), without and with 1 wt% ZnO as sintering additive, was used to consolidate green bodies by dry pressing. The pure ZST powder was also dispersed in aqueous media to obtain stable suspensions with high solid loadings. Free flowing spherical homogeneous granules were prepared by freeze granulation and used to consolidate ZST green bodies by dry pressing (FG-ZST). The effects of processing variables and sintering temperature (1300–1450 °C) on densification and on the structural, mechanical and electrical properties of ZST ceramics were systematically investigated. Our study clearly reveals the superior properties of FG-ZST ceramics, which derive from an enhanced sintering behaviour associated with the absence of sintering additives.

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Graphical abstract: Fostering the properties of Zr0.8Sn0.2TiO4 (ZST) ceramics via freeze granulation without sintering additives