Atmospheric Spray Freeze-Drying: Numerical Modeling and Comparison With Experimental Measurements

Atmospheric Spray Freeze-Drying: Numerical Modeling and Comparison With Experimental Measurements

Israel Borges Sebastião, Thomas D. Robinson, Alina Alexeenko

Abstract

Atmospheric spray freeze-drying (ASFD) represents a novel approach to dry thermosensitive solutions via sublimation. Tests conducted with a second-generation ASFD equipment, developed for pharmaceutical applications, have focused initially on producing a light, fine, high-grade powder consistently and reliably. To better understand the heat and mass transfer physics and drying dynamics taking place within the ASFD chamber, 3 analytical models describing the key processes are developed and validated. First, by coupling the dynamics and heat transfer of single droplets sprayed into the chamber, the velocity, temperature, and phase change evolutions of these droplets are estimated for actual operational conditions. This model reveals that, under typical operational conditions, the sprayed droplets require less than 100 ms to freeze. Second, because understanding the heat transfer throughout the entire freeze-drying process is so important, a theoretical model is proposed to predict the time evolution of the chamber gas temperature. Finally, a drying model, calibrated with hygrometer measurements, is used to estimate the total time required to achieve a predefined final moisture content. Results from these models are compared with experimental data.

Keywords

spray freeze-drying; thermodynamics; simulations; proteins; freeze-drying/lyophilization; powder technology; mathematical model

Hydroxypropylcellulose as matrix carrier for novel cage-like microparticles prepared by spray-freeze-drying technology

Hydroxypropylcellulose as matrix carrier for novel cage-like microparticles prepared by spray-freeze-drying technology

Shaofeng Weia, Yueqin Mab, Jing Luoa, Xiaoru Hea, Pengfei Yuea, Zhiyu Guana, Ming Yanga

Abstract

The objective of this study is to design novel dissolution-enhanced microparticles loaded poorly soluble drug nanocrystals used a low viscosity of hydroxypropylcellulose (HPC) as matrix carrier. An interesting approach combined homogenization and the spray-freeze-drying technique was developed. The results demonstrated that the ratio of HPC to drug played an important role in size-reduction efficiency of drug during homogenization. And the formation of cage-like structure of the composite particles depended on ratio of HPC to drug. The spray-freeze-dried composite particles with HPC ratio of 1:2, 1:1 and 2:1 possessed excellent redispersibility, which attributed to its porous matrix and large surface area (3000 m2/g). The dissolution of spray-freeze-dried composite particles with higher ratios of HPC (1:2 and 1:1) was significantly enhanced, which attributed to the particle size reduction of drug. The HPC could immobilize drug nanocrystals in its cage-like structure and prevent it from the subsequent agglomeration during storage. In conclusion, the prepared cage-like microparticles is a promising basis for further formulation development.

Keywords

Hydroxypropylcellulose; Nanocrystals; Cage-like microparticles; Spray-freeze-drying; Redispersibility

Happy New Year!

Season Greetings 2014

 

 

 

 

 

 

 

PowderPro wish all our customers and partners a happy and successful 2016!

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Categorized as News

Ceramics Expo 2016

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Welcome to PowderPro’s booth No 128 at the Ceramics Expo April 26-28, 2016 in Cleveland, Ohio. We look forward meeting you and to discuss how our Freeze Granulation technology can improve the granule quality of your powder and binder system for to make high quality ceramics.

At this Ceramics show we look forward to meet PowderPro’s largest market, where we have a lot of applications trough out the years.

Additive-free hot-pressed silicon carbide ceramics-A material with exceptional mechanical properties

Additive-free hot-pressed silicon carbide ceramics-A material with exceptional mechanical properties

P. Šajgalík, J. Sedláček, Z. Lenčéš, J. Dusza, H.-T. Lin

Abstract

Densification of silicon carbide without any sintering aids by hot-pressing and rapid hot pressing was investigated. Full density (>99% t.d.) has been reached at 1850 °C, a temperature of at least 150–200 °C lower compared to the up to now known solid state sintered silicon carbide powders. Silicon carbide was freeze granulated and heat treated prior the densification. Evolution of microstructure, mechanical properties and creep behavior were evaluated and compared to reference ceramics from as received silicon carbide powder as well as those of commercial one. Novel method results in dense ceramics with Vickers hardness and indentation fracture toughness of 29.0 GPa and 5.25 MPa m1/2, respectively. Moreover, the creep rate of 3.8 × 10−9 s−1 at 1450 °C and the load of 100 MPa is comparable to the commercial α-SiC solid state sintered at 2150 °C.

Keywords

Silicon carbide, Hot pressing, Microstructure, Mechanical properties, Creep resistance, freeze granulation

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