Spray Freeze-Drying as an Alternative to the Ionic Gelation Method to Produce Chitosan and Alginate Nano-Particles Targeted to the Colon

Spray Freeze-Drying as an Alternative to the Ionic Gelation Method to Produce Chitosan and Alginate Nano-Particles Targeted to the Colon

Gamboa A, Araujo V, Caro N, Gotteland M, Abugoch L, Tapia C

Abstract

Chitosan and alginate nano-composite (NP) carriers intended for colonic delivery containing prednisolone and inulin were obtained by two processes. Spray freeze-drying using chitosan (SFDC) or alginate (SFDA) was proposed as an alternative to the traditional chitosan-tripolyphosphate platform (CTPP). NPs were fully characterised and assessed for their yield of particles; level of prednisolone and inulin release in phosphate and Krebs buffers; and sensitivity to degradation by lysozyme, bacteria and faecal slurry. NPs based on chitosan showed similar properties (size, structure, viscoelastic behaviour), but those based on SFDC showed a higher mean release of both active ingredients, with similar efficiency of encapsulation and loading capacity for prednisolone but lower for inulin. SFDC was less degraded in the presence of lysozyme and E. coli and was degraded by B. thetaiotaomicron but not by faecal slurry. The results obtained with SFDA were promising because this NP showed good encapsulation parameters for both active ingredients and biological degradability by E. coli and faecal slurry. However, it will be necessary to use alginate derivatives to reduce its solubility and improve its mechanical behaviour.

KEYWORDS:

alginate; biodegradable polymers; chitosan; colonic drug delivery; nanoparticles; spray freeze-drying

Nanoembedded Microparticles for Stabilization and Delivery of Drug-Loaded Nanoparticles

Nanoembedded Microparticles for Stabilization and Delivery of Drug-Loaded Nanoparticles

Bohr A, Water J, Beck-Broichsitter M, Yang M

Abstract

Nanoparticle-based pharmaceutical products are currently finding their way onto the market as a popular strategy to improve the therapeutic efficacy of numerous drugs, hereunder medications for a targeted treatment of severe diseases (e.g., cancer). Drug-loaded polymer and lipid nanoparticles are typically produced via solventbased methods and result in colloidal suspensions, which often suffer from physical and chemical instability (e.g., formation of aggregates) resulting in loss of functionality. There are various ways to stabilize such nanoparticlebased formulations including addition of ionic materials to provide electrostatic repulsion or polymer materials forming a steric barrier between the particles. However, for long-term stability often water needs to be removed to obtain a dry product. For this purpose atomization-based techniques such as spray-drying and spray freeze-drying are frequently used to remove water from the nanoparticle suspensions and to form tailored powder products (e.g., nanoembedded microparticles (NEMs)). NEMs provide an excellent vehicle for both stabilization of nanoparticles and delivery of the nanoparticles to their intended site of action. Excipients such as sugars and biocompatible polymers are used to prepare the surrounding, stabilizing matrix. Further, these “Trojan” vehicles are compatible with a wide range of therapeutic molecules, nanocarriers and applications for different routes of administration. The preparation, properties and stability of these NEMs are described in this review and their application and future development are discussed.

Keywords: Nanoembedded microparticles, drug delivery, spray freeze drying, nanomedicine, nanoparticles, spray drying

Please contact us and we will further discuss the opportunities with Freeze Granulation on your powder system and read more on technology and we propose a Granulation Test of your powder system.

Thermally sensitive nanoparticles

Freeze Granulation of thermally sensitive nanoparticles

By using Freeze Granulation, spray freeze drying (SFD), you can produce dry-powder aggregates of thermally sensitive nanoparticles. Dry powder inhaler (DPI) delivery of therapeutic nanoparticles requires the nanoparticles to be transformed into inhalable micro-scale aggregate structures (i.e. nano-aggregates). With Freeze Granulation you will be able to optimize the aerosolization efficiency of the nano-aggregates, while keeping the morphology, production yield, flowability, and aqueous reconstitution in the desirable range.

Please contact us and we will further discuss the opportunities with Freeze Granulation in your powder system and read more on technology and a Granulation Test of your powder system.

Granule of thermally sensitive nanoparticles
Granule of thermally sensitive nanoparticles

 

Nano ice formation in granules

Nano ice in granules by Freeze Granulation

Nano ice formation in granules by Freeze Granulation process is a key factor for the unique homogeneity of particles and binders achieved in the resulting granules. This is especially important for nanopowders, fine particles and binders where migration of these could occur during conventional drying, like spray drying.

Please contact us and we will further discuss the opportunities with Freeze Granulation on your powder system and read more on technology and we propose a Granulation Test of your powder system.

Granule with nano-ice and nanopowder
Nano-ice formation in granules of nanoparticles

Applications for Freeze Granulation

Typical applications for Freeze Granulation are homogeneous granulation and drying of engineering (advanced, fine, high-performance) ceramic powders; oxides (alumina (Al2O3), zirconia (ZrO2), silica (SiO2)), nitrides (silicon nitride (Si3N4)) and carbides (SiC) and also granulation of powders of metal oxides, plasma spraying, nanomaterials (nanopowders), diamonds (PCD/CBN inserts), LED Lighting, pyrotechnicals (igniters, delay elements) and drying of pharmaceuticals and drugs, and for drying of biomaterials like proteins, enzymes and fine chemicals.

Nanoparticles processing

Processing of nanoparticles
Processing of nanoparticles

Processing of nanoparticles using Freeze Granulation, Spray Freeze Drying, you will get optimal properties of your nanoparticles when mixing them with other powders or materials. The homogeneity of the powder mixture will be kept throughout the process steps, in spraying, freezing and drying, resulting in a dry granulate with homogeneously distributed nanoparticles.

Thermally sensitive nanoparticles

Freeze Granulation

By using Freeze Granulation, spray freeze drying (SFD), you can produce dry-powder aggregates of thermally sensitive nanoparticles. Dry powder inhaler (DPI) delivery of therapeutic nanoparticles requires the nanoparticles to be transformed into inhalable micro-scale aggregate structures (i.e. nano-aggregates). With Freeze Granulation you will be able to optimize the aerosolization efficiency of the nano-aggregates, while keeping the morphology, production yield, flowability, and aqueous reconstitution in the desirable range.

Deagglomeration of nanoparticles and other submicron powders

By applying Freeze Granulation on your agglomerated nanoparticles or submicron powders you will be able to deagglomerate them forming a homogeneous well-dispersed particles or mixture of particles.

Please contact us and we will further discuss the opportunities with Freeze Granulation on your powder system and read more on technology and we propose a Granulation Test of your powder system.

Processing of nanoparticles
Processing of nanoparticles

Handling and Processing of Nanopowders

We have long experience in handling and processing of nanoparticles/nanopowders, for example, mix and granulate different powders and binders for to achieve improved homogeneity and increased performance of the final product.

Granule of nanoparticles
Granule of nanoparticles

Freeze granulation gives the possibility to granulate nanoparticles/nanopowders achieving granules with high degree of homogeneity which are easily re-dispersed (if applicable) in a liquid or dis-integrated at a pressing operation. This is owing to the week inter-particle bonding compare to what is obtained in conven­tional drying. Consequently, the nanosized material properties will be preserved, i.e. nano will still be nano. Freeze-drying also prevents oxidation of metals or non-oxide materials as conventional drying do not, especially critical for nanopowders.

Processing of nanoparticles
Processing of nanoparticles