Dry powder formulation of plasmid DNA and siRNA for inhalation

Dry powder formulation of plasmid DNA and siRNA for inhalation

Chow MY, Lam JK

Abstract

Nucleic acid therapeutics has huge potential for the treatment of a wide range of diseases including respiratory diseases. Plasmid DNA (pDNA) and small interfering RNA (siRNA) are the two most widely investigated nucleic acids for therapeutic development. However, efficient and safe delivery of nucleic acids is still a major hurdle in translating nucleic acid therapy into clinical practice. For the treatment of respiratory diseases, administration via inhalation is the most direct and effective way to deliver therapeutic nucleic acids to the lungs. Although liquid aerosol formulation is investigated in most of the studies, it is not desirable in terms of maintaining the stability of nucleic acid especially during long-term storage. This problem could be circumvented by formulating the therapeutic nucleic acids into dry powder for inhalation, and should be considered as the future direction of developing inhalable nucleic acids. In this review, the three major particle engineering methods investigated for the preparation of inhalable pDNA and siRNA formulations, including spray drying (SD), spray freeze drying (SFD) and supercritical fluid (SFC) drying, are discussed and compared. Moreover, common assessment methods and the challenges of evaluating the biological activities of inhalable nucleic acid powders are also reviewed.

Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: Spray drying versus spray freeze drying preparation

Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: Spray drying versus spray freeze drying preparation

Yu H, Teo J, Chew JW, Hadinoto K

Abstract

Inhaled nano-antibiotics have recently emerged as the promising bronchiectasis treatment attributed to the higher and more localized antibiotic exposure generated compared to native antibiotics. Antibiotic nanoparticle complex (or nanoplex in short) prepared by self-assembly complexation with polysaccharides addresses the major drawbacks of existing nano-antibiotics by virtue of its high payload and cost-effective preparation. Herein we developed carrier-free dry powder inhaler (DPI) formulations of ciprofloxacin nanoplex by spray drying (SD) and spray freeze drying (SFD). d-Mannitol and l-leucine were used as the drying adjuvant and aerosol dispersion enhancer, respectively. The DPI formulations were evaluated in vitro in terms of the (1) aerosolization efficiency, (2) aqueous reconstitution, (3) antibiotic release, and (4) antimicrobial activity against respiratory pathogen Pseudomonas aeruginosa. The SFD powders exhibited superior aerosolization efficiency to their SD counterparts in terms of emitted dose (92% versus 66%), fine particle fraction (29% versus 23%), and mass median aerodynamic diameter (3μm versus 6μm). The superior aerosolization efficiency of the SFD powders was attributed to their large and porous morphology and higher l-leucine content. While the SFD powders exhibited poorer aqueous reconstitution that might jeopardize their mucus penetrating ability, their antibiotic release profile and antimicrobial activity were not adversely affected.

KEYWORDS:

Antibiotic nanoparticles, Chronic lung infection, Cystic fibrosis, Dry powder inhaler, Pulmonary drug delivery, spray freeze drying

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

Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

Solidification of nanosuspensions for the production of solid oral dosage forms and inhalable dry powders

Maria Malamatari, Satyanarayana Somavarapu, Kevin M.G. Taylor & Graham Buckton

Abstract

Introduction: Nanosuspensions combine the advantages of nanotherapeutics (e.g. increased dissolution rate and saturation solubility) with ease of commercialisation. Transformation of nanosuspensions to solid oral and inhalable dosage forms minimises the physical instability associated with their liquid state, enhances patient compliance and enables targeted oral and pulmonary drug delivery.
Areas covered: This review outlines solidification methods for nanosuspensions. It includes spray and freeze drying as the most widely used techniques. Fluidised-bed coating, granulation and pelletisation are also discussed as they yield nanocrystalline formulations with more straightforward downstream processing to tablets or capsules. Spray-freeze drying, aerosol flow reactor and printing of nanosuspensions are also presented as promising alternative solidification techniques. Results regarding the solid state, in vitro dissolution and/or aerosolisation efficiency of the nanocrystalline formulations are given and combined with available in vivo data. Focus is placed on the redispersibility of the solid nanocrystalline formulations, which is a prerequisite for their clinical application.
Expert opinion: A few solidified nanocrystalline products are already on the market and many more are in development. Oral and inhalable nanoparticle formulations are expected to have great potential especially in the areas of personalised medicine and delivery of high drug doses (e.g. antibiotics) to the lungs, respectively.

Keywords

  • dry powder for inhalation, matrix former, nanosuspension, redispersibility, solidification, solid oral dosage forms, spray-freeze drying

 

Inhalable nanocomposite microparticles: Preparation, characterization and factors affecting formulation

Inhalable nanocomposite microparticles: Preparation, characterization and factors affecting formulation

Elsayed I, AbouGhaly MH

Abstract

INTRODUCTION:

Nanocomposite microparticles are intelligent carriers utilised for pulmonary drug delivery. These carriers are composed of drug-encapsulated nanoparticles dispersed in microstructures of polysaccharides. Upon administration, the inhaled microparticles can penetrate and be deposited deeply in the lung due to their adjusted aerodynamic particle size. Subsequently, the nanoparticles are released into the lung and are retained there for a prolonged time due to their resistance to immunological opsonisation, engulfment and digestion.

AREA COVERED:

Nanocomposite microparticles may be prepared by spray drying, spray freeze drying, spray drying fluidised bed granulation or dry coating techniques. The selection of the included excipients, preparation technique and optimisation of the operational parameter play a significant role in the determination of the aerodynamic particle size, redispersibility of the nanoparticles, morphology, yield, moisture content, flowability and in vitro drug release. Moreover, the in vivo behaviour of this novel carrier may be optimised and traced by studying the lung deposition of the inhaled particles and the biological activity of the encapsulated drug.

EXPERT OPINION:

Nanocomposite microparticles have been found to be superior to both nanoparticles and microparticles and may represent a promising carrier for pulmonary drug delivery.

KEYWORDS:

aerodynamic particle size, lung deposition, nanocomposite microparticles, spray freeze 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.

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.

Pharmaceutical spray freeze drying

Pharmaceutical spray freeze drying

Stefan Wanning, Richard Süverkrüp, Alf Lamprecht

Abstract

Pharmaceutical spray-freeze drying (SFD) includes a heterogeneous set of technologies with primary applications in apparent solubility enhancement, pulmonary drug delivery, intradermal ballistic administration and delivery of vaccines to the nasal mucosa. The methods comprise of three steps: droplet generation, freezing and sublimation drying, which can be matched to the requirements given by the dosage form and route of administration. The objectives, various methods and physicochemical and pharmacological outcomes have been reviewed with a scope including related fields of science and technology.

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

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.

How to avoid doughnut or donut shaped granules?

By using Freeze Granulation – Spray Freeze Drying – you will be able to avoid donut-shaped granules.

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.

Interested in test-granulation of your material?

If you would like to test-granulate your powders or chemicals using Freeze Granulation, please contact us for details. You send your material and binders to us, we make the test-granulation using freeze granulation and then send the granulated material (granulaes) back to you for your evaluation and testing.

Freeze granulation is considered to be a natural tool in most kind of material processing and development where optimal material performance is to be reached. PowderPro provides test granulations to reduced cost to evaluate the performance regarding your specific material system and application.

When purchasing of granulation equipment, PowderPro provides help in concepts for suspension formulation/preparation and how to operate the equipment to achieve high yield and high-quality granules.

 

LS-2 - Lab-scale Freeze Granulator