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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

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

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

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

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.