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Effects of Non-covalent Functionalization and Initial Mixing Methods on SWNT/PP and SWNT/EVOH Composites

Mahesh Parit, Virginia A. Davis

Abstract

We report that a simple, low-cost type of spray-freeze drying (SFD) significantly improves the dispersion of single-walled carbon nanotubes (SWNTs) in thermoplastic polymers. Conventional SFD requires costly specialized equipment and large amounts of material, both of which are impediments to laboratory research on nanomaterial composites. Our method uses more readily available equipment and can be adapted to use milligrams to grams of material. A household spray bottle containing an aqueous nanomaterial dispersion is used to spray the dispersion into a dish of liquid nitrogen. The resulting material is then lyophilized in a standard laboratory freeze dryer. The usefulness of this simplified method was explored by comparing the properties of polypropylene (PP) composites produced by this method to those produced by a previously reported rotary evaporation method in which the dispersion is vacuum-dried onto the polymer. The role of the initial dispersion state was explored by using pristine SWNTs as well as SWNTs stabilized by two common SWNT stabilizers: polyvinylpyrrolidone (PVP) and sodium dodecyl sulfate. Based on rheological, thermal, and morphological characterization, the porous friable structures produced by SFD resulted in better SWNT dispersion compared to composites produced by a previously reported rotary evaporation method. However, the PP/PVP-SWNT nanocomposites produced by both methods contained large aggregates. To verify that this aggregation behavior was the result of thermodynamic incompatibility between PP and PVP, ethylene vinyl alcohol (EVOH) nanocomposites containing PVP-SWNT were also produced using the SFD method. The results of this research show how a low-cost alternative to SFD along with careful consideration of compatibility is a promising approach to produce nanocomposites.

Keywords

Functionalization, Colloids, Nanocomposites, Carbon nanotubes, Polymers

Inhalable Protein Powder Prepared by Spray-Freeze-Drying Using Hydroxypropyl-β-Cyclodextrin as Excipient

Jason C. K. Lo, Harry W. Pan, Jenny K. W. Lam

Abstract

The prospect of inhaled biologics has garnered particular interest given the benefits of the pulmonary route of administration. Pertinent considerations in producing inhalable dry powders containing biological medicines relate to aerosol performance and protein stability. Spray-freeze-drying (SFD) has emerged as an established method to generate microparticles that can potentially be deposited in the lungs. Here, the SFD conditions and formulation composition were evaluated using bovine serum albumin (BSA) as a model protein and 2-hydroxypropyl-beta-cyclodextrin (HPβCD) as the protein stabilizer. A factorial design analysis was performed to investigate the effects of BSA content, solute concentration of feed solution, and atomization gas flow rate on dispersibility (as an emitted fraction), respirability (as fine particle fraction), particle size, and level of protein aggregation. The atomization gas flow rate was identified as a significant factor in influencing the aerosol performance of the powder formulations and protein aggregation. Nonetheless, high atomization gas flow rate induced aggregation, highlighting the need to further optimize the formulation. Of note, all the formulations exhibited excellent dispersibility, while no fragmentation of BSA occurred, indicating the feasibility of SFD and the promise of HPβCD as an excipient.

Keywords

Aerosolization, cyclodextrin, factorial design, inhalation, protein delivery, pulmonary delivery, spray-freeze-drying

Spray Freeze Drying: A novel process for the drying of foods and bioproducts

Padma Ishwarya S, Anandharamakrishnan Chinnaswamy, Andrew George Frederick Stapley

Abstract

Spray-freeze-drying (SFD) is an unconventional freeze drying technique that produces uniquely powdered products whilst still including the benefits of conventionally freeze dried products. SFD has potential applications in high value products due to its edge over other drying techniques in terms of product structure, quality, and the retention of volatiles and bioactive compounds. In cases where other drying techniques cannot provide these product attributes, SFD stands out despite the costs and complexities involved. This paper outlines the principles, methods, significant process parameters, particle morphology and quality aspects of SFD. Recent developments in this technique are reviewed including ultrasonic spray-freeze-drying, the application of computational fluid dynamics and mathematical modelling, and the incorporation of new technologies to improve product quality. In addition, the advantages, limitations and future scope for research in the field of SFD are discussed.

A meticulous overview on drying-based (spray-, freeze-, and spray-freeze) particle engineering approaches for pharmaceutical technologies

Abstract

Drying is an indispensable operation in the preparation of pharmaceutical powders and always remained one of the energetic tasks in the pharmaceutical industry. Improving the stability, solubility, and dissolution of pharmaceutical products are being prime objectives of the drying process, intending to produce the products loving the dry state. Although there are voluminous literatures available concerning drying operations, there is scant information available regarding the applicability of drying in drug delivery and process scale-up. The current communication embodies the different particle engineering technologies of drying viz. spray-, freeze-, and spray-freeze drying. In addition, potential uses of drying in the taste masking, and the development of inhalable powders presented briefly. Recent advancements in the drying of novel drug delivery systems is the major focus of the present review. In our opinion, the commercial aspects, regulatory guidelines, and scale-up strategies presented herein provide an opportunity to readers, researchers, and industrialists to ruin the critical issues during drying operations and aid in developing quality pharmaceutical technologies.

Keywords

Particle engineering, shell formation, spray drying, freeze drying, solubility, crystallinity

Development and validation of an asymptotic solution for a two-phase Stefan problem in a droplet subjected to convective boundary condition

Saad Akhtar, Minghan Xu, Agus P. Sasmito

Abstract

Droplet solidification is governed by classical Stefan problems which have been commonly treated as a single-phase problem by the majority of the studies in the literature. This approach, however, is unable to capture the initial temperature and the start of freezing time correctly. The treatment of two-phase Stefan problem in spherical coordinates is limited. No known exact solution exists, albeit numerical solutions and asymptotics have proven to be useful. We present a singular perturbation solution in the limit of low Stefan number and arbitrary Biot number for the two-phase Stefan problem in a finite spherical domain. An asymptotic solution is developed for a droplet at a non-freezing initial temperature subjected to a convective boundary condition at the surface. The solution is developed for both long-time and short-time scales. The results from asymptotic expansion method are validated with the experimental results in the literature and are further verified by a numerical model of a freezing droplet using enthalpy–porosity method. The sensitivity of the asymptotic solution to the droplet initial temperature, Biot number, and Stefan number has also been studied. The results indicate that the solution from perturbation series and enthalpy–porosity method agrees to within 1%–10% for temperature profile and overall freezing times over a wide range of practical values for initial temperature, Stefan and Biot numbers for the application of spray freezing. Our perturbation series solution is also able to capture the effect of initial temperature on the overall freezing time of the droplet.

Keywords

Perturbation series solution, Asymptotic expansion, Droplet freezing, Two-phase Stefan problem, Enthalpy–porosity method

Formulation and optimization of sildenafil citrate-loaded PLGA large porous microparticles using spray freeze-drying technique: A factorial design and in-vivo pharmacokinetic study

Hend Shahin, Bhavani Prasad Vinjamuri, Azza A.Mahmoud, Suzan M.Mansour, Mahavir Bhupal Chougule, Lipika Chablani

Abstract

The oral administration of sildenafil citrate (SC) for the treatment of pulmonary arterial hypertension is associated with several drawbacks. The study aimed to design and formulate SC-loaded inhalable poly (lactic-co-glycolic acid) [PLGA] large porous microparticles (LPMs) for pulmonary delivery. A factorial design was used to study the effect of the composition of LPMs on physicochemical properties. The study also evaluated the effect of glucose and L-leucine concentration on the formulation. The developed LPMs demonstrated an acceptable yield% (≤48%), large geometric particle size (>5µm) with a spherical and porous surface, and sustained drug release (up to 48 h). Increasing the concentration of poly(ethyleneimine) from 0.5% to 1% in SC-loaded LPMs led to an increase in entrapment efficiency from ~3.02% to ~94.48%. The optimum LPMs showed adequate aerodynamic properties with a 97.68 ± 1.07% recovery, 25.33 ± 3.32% fine particle fraction, and low cytotoxicity. Intratracheal administration of LPMs demonstrated significantly higher lung deposition, systemic bioavailability, and longer retention time (p < 0.05) compared to orally administered Viagra® tablets. The study concluded that SC-loaded LPMs could provide better therapeutic efficacy, reduced dosing frequency, and enhanced patient compliance.

Keywords

Sildenafil citrate, Large porous microparticles, Spray-freeze drying, Pulmonary arterial hypertension, Pulmonary drug delivery, Inhalable dry powder, Design of experiment

The application of freeze-drying as a production method of drug nanocrystals and solid dispersions – A review

Emilia Jakubowska, Janina Lulek

Abstract

This work reviews the examples of the application of lyophilization and its cryogenic modifications as the production method of solid dispersions and drug nanocrystals, two formulation approaches aimed at increasing the solubility, dissolution rate and oral bioavailability of poorly water soluble drugs. A brief recapitulation of freeze-drying basics is presented and the review is organized according to application and product type, with the consideration of different cryogenic techniques, e.g. spray freezing into liquid, as well as the combinations of lyophilization with other nanonization methods in pharmaceutical technology. The review focuses on freeze-drying as a particle engineering tool for the size reduction and surface area enhancement in the generation of nanosized drug particles, both as simple nanocrystals and as their dispersions within water soluble micro- or nanoparticulate matrices, instead of the use of lyophilization as a mere drying or solidification method. Therefore, attention is given to the relationships between formulation and process parameters (e.g. freezing rate), and the properties of the obtained material: particle size, porosity, surface area, morphology, polymorphism and dissolution behavior.

Keywords

Lyophilization, Freeze-drying, Nanocrystals, Solid dispersions, Nanonization

Influence of three types of freezing methods on physicochemical properties and digestibility of starch in frozen unfermented dough

Yong Yang, Shuaishuai Zheng, Zhen Li, Zhili Pan, Zhongmin Huang, Jianzhong Zhao, Zhilu Ai

Abstract

Three types of freezing methods, namely, spiral tunnel freezing method (SF), cryogenic refrigerator freezing method (RF) and liquid nitrogen spray freezing method (LF), were applied to frozen unfermented dough. The particle size distribution and SEM results showed freezing methods reduced the average particle size of starch granules and destroyed the surface microstructure, especially RF, and the damaged starch content and swelling power of starch after treatment increased. Gelatinization and pasting properties of starches changed to varying degrees, indicating freezing methods caused the internal rearrangement of starch molecules. This view could also be inferred from X-ray diffraction (XRD) and Fourier Transform infrared spectroscopy (FT-IR) data. The relative crystallinity (35.51%–38.56%) and the R_1047/1022 (0.562–0.590) were increased, compared with the control (32.44%, 0.559, respectively). Meanwhile, freezing treatment improved the digestibility of starch by promoting the combination of enzymes and starch, especially RF. Larger ice crystals formed by RF with slower freezing rate produced larger damage to starch structure, more likely to promote the binding with enzymes. LF with faster freezing rate had less effect on the starch composition than RF and SF with slower freezing rate. The data obtained clarified the influence of freezing methods on the structure and properties of starch in a yeast-free dough system, and enriched the knowledge regarding the effect of freezing technology on food components.

Keywords

Freezing methods, Frozen unfermented dough, Starch digestibility, Ordered structure, Relative crystallinity

Effect of Ca2+ and Mg2+ ions on the sintering and spectroscopic properties of cr‐doped yttrium aluminum garnet ceramics

Przemysław Gołębiewski, Helena Węglarz, Magdalena Nakielska, Anna Wajler

Abstract

In this work, we investigated the effects of Ca2+ and Mg2+ ions and annealing temperature on the spectroscopic parameters of chromium‐doped yttrium aluminum garnet ceramics (Cr:YAG). Samples were obtained with either a separate or a simultaneous addition of calcium and magnesium oxides. To achieve this, aqueous suspensions were prepared using Y2O3, Al2O3, Cr2O3, MgO, and CaO high‐purity powders as raw materials. The obtained suspensions were freeze‐granulated, pressed into pellets, debinded, and subjected to reactive sintering in vacuum at 1715°C for 6 h. Each material was annealed in air with temperatures between 1300 and 1700°C. Samples were also compared to Cr:YAG ceramics with the addition of silica as a sintering aid. All the materials obtained were then exposed to 445 nm excitation, and emission spectra in the visible and infrared wavelengths were recorded. The results showed that the emission spectra of Cr:YAG ceramics varied according to the annealing conditions: as‐sintered samples exhibited strong emissions of around 680 nm and, after air annealing, of around 1400 nm. This phenomenon is attributed to the Cr3+→Cr4+ transition. Samples doped solely with MgO exhibited the highest emission intensity in the infrared region. Thus, Mg2+ ions provided the best conversion efficiency of chromium ions.

Keywords

Cr:YAG, Q‐switching, transparent ceramics, yttrium aluminum garnet

Formulation and evaluation of inhalable microparticles of Rizatriptan Benzoate processed by spray freeze-drying

Mahsa Keyhan shokouh, Homa Faghihi, Majid Darabi, Maryam Mirmoeini, Alireza Vatanara

Abstract

The aim of the current study was to prepare and evaluate inhalable microparticles of Rizatriptan benzoate in order to further benefit from its pulmonary delivery, the expected enhanced bioavailability and accelerated onset of action. The spray freeze drying (SFD) technique was used to produce microparticles consisting of a fixed amount of a sugar which was either mannitol or trehalose and an amino acid component including leucine, phenylalanine or serine. The powders were then characterized for particle size distribution, morphology, thermal properties and in vitro aerosolization performance. It was demonstrated that various formulations of inhalable Rizatriptan could be efficiently aerosolized and offered acceptable fine particle fraction (FPF) ranging up to 61.1%. In particular, a spray-freeze-dried powder composed of trehalose and phenylalanine showed the most superior inhalation performance (FPF = 61.1%), indicating better dispersion properties of those spherical porous microparticles with less adhesion and agglomeration. These results successfully demonstrated that Rizatriptan could be engineered into respirable microparticles to be proposed as a promising delivery system for fast and effective control of migraine attacks.

Keywords

Rizatriptan benzoate. Spray freeze drying, Inhalation, Carbohydrates, Amino acids