A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

A spray freeze dried micropellet based formulation proof-of-concept for a yellow fever vaccine candidate

Clénet D, Hourquet V, Woinet B, Ponceblanc H, Vangelisti M

Abstract

The stability of live-attenuated viruses is very challenging due to thermal sensitivity; therefore, solid form is usually required (often freeze-dried products). Micropellet technology is a lyophilization technology that has the potential to provide greater flexibility in the presentation of a given vaccine particularly in multi-dose format or in combination of different vaccines. As a novel vaccine alternative process, this spray freeze-dried (SFD) micropellet technology was evaluated using as a model a yellow fever virus produced in Vero cells (vYF). Screening of excipients was performed in order to optimize physico-chemical properties of the micropellets. Sugar/polymer-based formulations induced high glass transition temperature (Tg), adequate breaking force and attrition resistance of the SFD micropellets. These mechanical parameters and their stability are of considerable importance for the storage, the transport but also the filling process of the SFD micropellets. By adding excipients required to best preserve virus infectivity, an optimal sugar/polymer-based formulation was selected to build micropellets containing vYF. Monodisperse and dried micropellets with a diameter of about 530 µm were obtained, exhibiting similar potency to conventional freeze-dried product in terms of vYF infectious titer when both solid forms were kept under refrigerated conditions (2-8°C). Comparable kinetics of degradation were observed for vYF formulated in micropellets or as conventional freeze-dried product during an accelerated stability study using incubations at 25°C and 37°C over several weeks. The results from this investigation demonstrate the ability to formulate live-attenuated viruses in micropellets. Pharmaceutical applications of this novel vaccine solid form are discussed.

Keywords

Micropellets; formulation screening; freeze-drying; live-attenuated vaccine stability

Microwave heating synthesis and luminescence of NaY(WO4)2:(Ho3+, Yb3+) phosphors

Microwave heating synthesis and luminescence of NaY(WO4)2:(Ho3+, Yb3+) phosphors

Yang Yang, Hao Feng, Xiuguo Zhang

Abstract

NaY(WO4)(2):(Ho3+, Yb3+) phosphors were synthesized by microwave heating in an EDTA-mediated process. The samples were characterized by XRD, FT-IR, SEM, and fluorescence spectrophotometer. The XRD and FT-IR results show that the samples have the tetragonal phase. The SEM results show that obtained samples have octahedral morphology. ‘Oriented attachment’ and ‘Ostwald ripening’ play key roles in the formation of octahedrons. The UC emission spectra of NaY(WO4)(2):(Ho3+, Yb3+) phosphors under 980 nm excitation show two intense bands corresponding to F-5(4) + S-5(2) -> I-5(8) and F-5(5) -> I-5(8) transitions of Ho3+ ions. Based on the energy level diagrams of Yb3+ and Ho3+, as well as the results of power dependence of UC emission intensities, possible excitation path ways for different bands are deduced. The green and red UC emissions of NaY(WO4)(2):(Ho3+, Yb3+) phosphors originate from the two-photon process. Also, the samples have good thermal stability.

Preparation and characterization of nano amitriptyline hydrochloride particles by spray freeze drying

Preparation and characterization of nano amitriptyline hydrochloride particles by spray freeze drying

Hu Y, Ma C, Sun M, Guo C, Shen J, Wang J, Nie F, Gao B.

Abstract

Aim: To investigate the enhancement of bioavailability by the usage of drug nanoparticles for increasing the efficacy of antidepressant therapeutic value. Materials & methods: Nano-amitriptyline HCI (AMT·HCl) particles were successfully prepared via a simple spray freeze drying (SFD) method.

Results: The as-prepared nanoparticles are amorphous instead of crystalline. The mean size of AMT·HCl nanoparticles is 90 nm. In in vitro evaluation, AMT·HCl nanoparticles have greatly improved the dissolution compared with pure bulk materials, which have potential for enhancing human bioavailability and diminishing toxic effect. A nanoparticle formation mechanism was also proposed.

Conclusion: These findings promote the development of antidepressant therapeutic evaluation based on the usage of AMT·HCl nanoparticles by SFD method and indicate that SFD is an alternative for a range of nanoparticle preparation in industrial pharmacy.

Keywords

evaluation; amitriptyline hydrochloride; antidepressants; bioavailability; nanocrystals; spray freeze drying

Atmospheric spray freeze drying of sugar solution with phage D29

Atmospheric spray freeze drying of sugar solution with phage D29

Alvin Ly, Nicholas B. Carrigy, Hui Wang, Melissa Harrison, Dominic Sauvageau, Andrew R Martin, Reinhard Vehring, Warren H Finlay

Abstract

Therapeutic bacteriophages offer a potential alternative approach in the treatment of drug resistant bacteria. In the present study, we examine the ability of atmospheric spray freeze-drying (ASFD) to process bacteriophage D29 into a solid dry formulation. Bacteriophage D29 is of particular interest due to its ability to infect Mycobacterium tuberculosis. A sugar solution containing bacteriophage D29 was sprayed and instantly frozen in a cold chamber. Cold drying gas was then passed through the chamber at a high flow rate and atmospheric pressure. Convective transport combined with the low temperature of the drying gas results in sublimation of ice, yielding a free-flowing, porous powder. The bacteriophages were atmospheric spray freeze-dried in solutions with varying concentrations of trehalose and mannitol. A solution of trehalose and mannitol at a mass ratio of 7:3 and a total mass concentration of 100 mg/mL led to powder with 4.9 ± 0.1% moisture content and an acceptable titer reduction of ∼0.6 logs. In comparison, a pure trehalose solution and a 1:1 ratio of trehalose and mannitol both had titer reductions of >1.5 logs. Spectroscopic analysis showed that trehalose in the powder was amorphous while mannitol completely crystallized during the drying process, both of which are desirable for preserving phage viability and storage in powders. The results highlight the potential for using ASFD as an alternative process in preserving biopharmaceutical products.

Inert particles as process aid in spray-freeze drying

Inert particles as process aid in spray-freeze drying

Fan Zhang, Xiaoyu Ma, Xiusheng Wu, Qing Xu, Wei Tian, Zhanyong Li

Abstract

Spray-freeze drying (SFD) is a novel and advanced drying technology in the production of high-value foods and pharmaceuticals. However, long drying time is still a disadvantage for the SFD applications. This constraint could be alleviated using inert particles. This article provides the experimental results on SFD of whole milk in an integrated spray-freeze and vacuum freeze drying equipment. The effects were quantified in terms of the SFD drying time and the properties of the obtained milk powder in relation to the size of stainless steel balls used as inert particles. It is shown that the drying time could be reduced to some extent due to inert particles embedded and the milk powder of reduced size has high porous microstructure.

Development of Inhalable Dry Gene Powders for Pulmonary Drug Delivery by Spray-Freeze-Drying

Development of Inhalable Dry Gene Powders for Pulmonary Drug Delivery by Spray-Freeze-Drying

Edina Vranic, Merima Sirbubalo, Amina Tucak, Jasmina Hadžiabdić, Ognjenka Rahić, Alisa Elezovic

Abstract

There is considerable potential for pulmonary gene therapy as a treatment for a number of conditions for which current treatment is inadequate. Delivering genes directly to the lungs by dry powder inhalers (DPIs) have attracted much attention due to better stability of genes. Formulating genes as powders for aerosol delivery is a challenge as it requires not only flowability and dispersibility of the powders but also maintaining gene stability and biological activity during manufacturing and delivery. In this review, we aim to provide an overview about the potentials of spray-freeze-drying (SFD) for the development of inhalable dry gene powders for pulmonary drug delivery. We will discuss the main steps involved within the production process (i.e., spraying, freezing and drying) and introduce different SFD methods which can successfully be used for the production of porous particles whose physical and aerosol characteristics are considered to be ideal for use in pulmonary drug delivery.

Establishment of evaluation method for gene-silencing by serial pulmonary administration of siRNA and pDNA powders: Naked siRNA inhalation powder suppresses luciferase gene expression in lung

Establishment of evaluation method for gene-silencing by serial pulmonary administration of siRNA and pDNA powders: Naked siRNA inhalation powder suppresses luciferase gene expression in lung

Takaaki Ito, Tomoyuki Okuda, Ryo Takayama, Hirokazu Okamoto

Abstract

In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.

Numerical analysis of in-flight freezing droplets: Application to novel particle engineering technology

Numerical analysis of in-flight freezing droplets: Application to novel particle engineering technology

Andrew Tait, Jonathan G.M. Lee, Bruce R.Williams, Gary A. Montague

Abstract

The freezing of a stream of free-falling monodispersed droplets was simulated through the development of numerical models in this work. Prediction of the freezing time and temperature transition of a single droplet is beneficial for optimisation of novel continuous spray freeze drying (cSFD) processes. Estimations of the vertical free-falling distance of the droplets in a slip stream and predictions of the chances of droplet coalescence greatly enhance process understanding and can be leveraged to direct equipment design and process development. A design space of droplet diameters in the range from 100 μm to 400 μm and ambient temperatures from −120 °C to −40 °C was explored. The rate of supercooling within the design space was predicted to range from 48 to 830 °C s−1 depending on the ambient temperature and droplet size. A comparison of the vertical free-falling distances of solitary droplets and streams of droplets at different temperatures showed that the terminal velocity of a vertically falling stream of droplets is always in excess of the terminal velocity of a solitary droplet of the same size. A difference of 1.35 m was predicted for the free-falling distance of a 400 μm droplet compared to a stream of droplets at −42 °C. A comparison between flow rates for consecutively generated 100 μm droplets showed that droplet coalescence was predicted at 0.05 Lh−1, whilst at 0.02 Lh−1 a separation distance of 23 μm was maintained thus preventing coalescence.

Keywords

Continuous spray freeze drying, Freeze drying, Lyophilisation, Freezing transitions, Freezing, Numerical modelling, Spray freezing

Fabrication of three-dimensional TKX-50 network-like nanostructures by liquid nitrogen-assisted spray freeze-drying method

Fabrication of three-dimensional TKX-50 network-like nanostructures by liquid nitrogen-assisted spray freeze-drying method

Xiong Cao, Yiping Shang, Kejuan Meng, Guodong Yue, Liyuan Yang, Yang Liu, Peng Deng, Lishuang Hu

Abstract

Design and fabrication of micro- and nanostructures for energetic materials have attracted more attention recently to improve safety properties and enhance detonation performance. Exploring and developing dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) with unique microstructures, an emerging high-energy-density material with superior comprehensive properties, is of great significance for the potential applications. In this work, we reported that three-dimensional (3D) TKX-50 network-like nanostructures were designed and fabricated successfully via the liquid nitrogen-assisted spray freeze-drying method. Characterization results suggested 3D TKX-50 network-like nanostructures were constructed by self-assembly of small nanoparticles. Furthermore, a nucleation-and-growth self-assembly formation mechanism of the network-like nanostructures depended on the different concentrations of the aqueous solution of TKX-50 was proposed in detail based on the experimental results. More interestingly, thermal analysis results demonstrated these novel 3D TKX-50 network-like nanostructures are much easier to be activated and have a lower decomposition temperature than the raw material, due to decrease in particle sizes, and the impact sensitivity of 3D TKX-50 network-like nanostructures become more sensitive than that of raw TKX-50. Their friction sensitivity of as-prepared samples is similar to the raw materials. Therefore, this work could provide a new prospect for fabrication and application of TKX-50 nanostructures.