Protein spheres prepared by drop jet freeze drying

Eggerstedt, Sören N.; Dietzel, Mathias; Sommerfeld, Martin; Süverkrüp, Richard; Lamprecht, Alf

doi:10.1016/j.ijpharm.2012.08.035

Cited by 35 publications

(11 citation statements)

References 15 publications

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“…Within the SFD process, shear stress at drop break-up is the main remaining stress factor, however, the unchanged activity of insulin confirmed the suitability of the process. Similar findings were reported earlier for other peptides and proteins, e.g., lysozyme and bovine serum albumin [10].…”

Section: Discussionsupporting

confidence: 92%

“…In principle, their internal morphologies show strong similarities to traditional freeze-drying cakes, however, due to the spherical shape and a narrow particle size distribution, lyospheres possess a very good powder flowability. In a previous publication from our research group, Eggerstedt et al [10] found the apparent density of the SFD microspheres to be in a range between 0.06 and 0.36 g/cm 3 , while the formulations with a solid content similar to the formulations in this study had an apparent density between 0.1-0.2 g/cm 3 . In the same study, the porosity was calculated to be ranging between 73.2 and 95.8% for SFD particles with varying solid content.…”

Section: Discussionsupporting

confidence: 46%

“…SFD was conducted with a method slightly modified and adapted from the method described earlier [10,11]. For droplet formation, a monodisperse droplet generator (MTG-01-G1, FMP Technology GmbH, Erlangen, Germany) with a nozzle diameter of 50 or 100 µm was installed on top of the spray tower.…”

Section: Preparation Of the Spray Freeze-dried Particlesmentioning

confidence: 99%

“…Spray freeze-dried particles are proposed here to offer a solution to the above-mentioned problematics. Generally, spray freeze drying (SFD) is a process in which a solution is dispersed into a freezing medium and dried by sublimation, resulting in lyophilized powders of high porosity, preferentially with spherically shaped particles [10][11][12]. Techniques differ in terms of nozzle type, freezing step, and drying procedure.…”

Section: Introductionmentioning

confidence: 99%

“…Omitting the direct contact of the sprayed droplets with the cryogenic liquid facilitated the process handling in many ways and is nowadays used in many cases [13]. The gentle processing of the active in this technique renders the drying of thermo-labile substances possible at low temperatures to produce peptide and protein formulations without activity loss of the biologicals [10]. Besides, specifically, the nasal administration of lyophilisates would have the significant benefit of rapid dissolution of the drug loaded particle on the mucosal surface.…”

Section: Introductionmentioning

confidence: 99%

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Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin

et al. 2021

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Pharmacologically active macromolecules, such as peptides, are still a major challenge in terms of designing a delivery system for their transport across absorption barriers and at the same time provide sufficiently high long-term stability. Spray freeze dried (SFD) lyospheres® are proposed here as an alternative for the preparation of fast dissolving porous particles for nasal administration of insulin. Insulin solutions containing mannitol and polyvinylpyrrolidone complemented with permeation enhancing excipients (sodium taurocholate or cyclodextrins) were sprayed into a cooled spray tower, followed by vacuum freeze drying. Final porous particles were highly spherical and mean diameters ranged from 190 to 250 µm, depending on the excipient composition. Based on the low density, lyospheres resulted in a nasal deposition rates of 90% or higher. When tested in vivo for their glycemic potential in rats, an insulin-taurocholate combination revealed a nasal bioavailability of insulin of 7.0 ± 2.8%. A complementary study with fluorescently labeled-dextrans of various molecular weights confirmed these observations, leading to nasal absorption ranging from 0.7 ± 0.3% (70 kDa) to 10.0 ± 3.1% (4 kDa). The low density facilitated nasal administration in general, while the high porosity ensured immediate dissolution of the particles. Additionally, due to their stability, lyospheres provide an extremely promising platform for nasal peptide delivery.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 46%

Section: Preparation Of the Spray Freeze-dried Particlesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spray Freeze Dried Lyospheres® for Nasal Administration of Insulin

et al. 2021

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Fabrication of biodegradable polyurethane microspheres by a facile and green process

Lin

Hsu

2014

J. Biomed. Mater. Res.

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Two different compositions of water-based biodegradable polyurethane (PU) in the form of homogeneous nanoparticles (NPs) were synthesized using biodegradable polyesters as the soft segment. The first PU (PU01) was based on poly(ε-caprolactone) (PCL) diol and the second PU (PU02) was based on 40% PCL diol and 60% polyethylene butylene adipate diol. The PU NP dispersions with different solid contents were sprayed into liquid nitrogen and resuspended in water to generate elastic microspheres (50-60 µm) with different nanoporosities. In vitro degradation analysis revealed that microspheres of PU02 (i.e., PU02 MS) degraded faster than those of PU01 (PU01 MS). Methylene blue was encapsulated during microsphere formation and the release was investigated. Microspheres made from a lower content (10%) of PU02 dispersion (i.e., PU02 MS_10) showed a greater burst release of methylene blue in 6 h, whereas those made from a higher content (30%) of PU01 dispersion (i.e., PU01 MS_30) revealed a prolonged release with a significantly lower burst release. Biocompatibility evaluation using L929 fibroblasts demonstrated that cells were attached and proliferated on microspheres after 24 h. On the other hand, microspheres may further self-assemble into films and scaffolds. Surface modification of microspheres by chitosan may modify the self-assembly behavior of microspheres. Microspheres could be stacked to form scaffolds with different macroporosities. Fibroblasts were successfully seeded and grown in the microsphere-stacked scaffolds. We concluded that the biodegradable and elastic microspheres may be facilely produced from a green and sustainable process with potential applications in drug release and three-dimensional cell culture.

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