Gas flow-assisted powder deposition for 3D printing of alfa-TCP: printing and sintering evaluations

In questa tesi, alfa TCP è impiegato per stampare 3D tablet e scaffold per scopi biomedici.ope

Harnessing Artificial Intelligence for the Next Generation of 3D Printed Medicines

Artificial intelligence (AI) is redefining how we exist in the world. In almost every sector of society, AI is performing tasks with super-human speed and intellect; from the prediction of stock market trends to driverless vehicles, diagnosis of disease, and robotic surgery. Despite this growing success, the pharmaceutical field is yet to truly harness AI. Development and manufacture of medicines remains largely in a ‘one size fits all’ paradigm, in which mass-produced, identical formulations are expected to meet individual patient needs. Recently, 3D printing (3DP) has illuminated a path for on-demand production of fully customisable medicines. Due to its flexibility, pharmaceutical 3DP presents innumerable options during formulation development that generally require expert navigation. Leveraging AI within pharmaceutical 3DP removes the need for human expertise, as optimal process parameters can be accurately predicted by machine learning. AI can also be incorporated into a pharmaceutical 3DP ‘Internet of Things’, moving the personalised production of medicines into an intelligent, streamlined, and autonomous pipeline. Supportive infrastructure, such as The Cloud and blockchain, will also play a vital role. Crucially, these technologies will expedite the use of pharmaceutical 3DP in clinical settings and drive the global movement towards personalised medicine and Industry 4.0

Biological and Medical Experiments on the Space Shuttle, 1981 - 1985

This volume is the first in a planned series of reports intended to provide a comprehensive record of all the biological and medical experiments and samples flown on the Space Shuttle. Experiments described have been conducted over a five-year period, beginning with the first plant studies conducted on STS-2 in November 1981, and extending through STS 61-C, the last mission to fly before the tragic Challenger accident of January 1986. Experiments were sponsored within NASA not only by the Life Sciences Division of the Office of Space Science and Applications, but also by the Shuttle Student Involvement Program (SSIP) and the Get Away Special (GAS) Program. Independent medical studies were conducted as well on the Shuttle crew under the auspices of the Space Biomedical Research Institute at Johnson Space Center. In addition, cooperative agreements between NASA and foreign government agencies led to a number of independent experiments and also paved the way for the joint US/ESA Spacelab 1 mission and the German (DFVLR) Spacelab D-1. Experiments included: (1) medically oriented studies of the crew aimed at identifying, preventing, or treating health problems due to space travel; (2) projects to study morphological, physiological, or behavioral effects of microgravity on animals and plants; (3) studies of the effects of microgravity on cells and tissues; and (4) radiation experiments monitoring the spacecraft environment with chemical or biological dosimeters or testing radiation effects on simple organisms and seeds

Advanced physical characterisation of milled pharmaceutical solids

Milling has been the key unit operation in controlling particle size of pharmaceutical powders at scale. The work carried out in this thesis is a comprehensive study of the stability of pharmaceutical solids post-milling and upon storage, from molecular level up to bulk handling scale. It is an attempt to fill key gaps in knowledge with regard to the anomalous behaviour and physical instability of milled powder through the development of advanced novel techniques. The physical instability of milled or amorphous pharmaceutical powders often manifest in changes in derived powder properties. Moisture induced dimensional changes of amorphous lactose compacts were monitored by in-situ environmental controlled optical profilometry. The complex volumetric behaviour involves glassy-rubbery phase transition followed by amorphous-crystalline transformation under the influence of water. These associated changes were not observed in physical aging of amorphous lactose compacts by measuring specific surface area. At the molecular level these physical changes are governed by relaxation processes. By operating within the linear viscoelastic region, low strain uni-axial indentation of small molecule organic glasses at a range of temperature generated master curves using WLF analysis. Viscoelastic behaviour of these materials were determined to be controlled by local β-relaxation around the glass transition rather than globally for polymers. At the bulk level, due to the non-equilibrium nature of milled and amorphous powders, their surface energies tends to be significantly higher than the equivalent crystalline forms. This can be detrimental as highly cohesive and poor flowing powders are difficult to process. The unconfined compression test was adapted to measure cohesion of small weak pharmaceutical powder compacts. More significantly, a positive relationship was confirmed between surface energetics and cohesion of modified D-mannitol. At the particle level, the mechanism(s) by which milling or micronisation creates low levels of amorphicity remains unclear. MOUDI fractionation of bulk micronised α-lactose monohydrate and characterisation of fine fractions has clearly demonstrated that micronisation as well as mechanical particle size reduction also generates low levels of highly amorphous ultrafine particles within bulk crystalline powder which will have a significant effect on powder physical stability post-milling and upon storage. In conclusion, using the novel techniques developed here, significant progress has been towards understanding the physical behaviour of milled and amorphous pharmaceutical solids

Quality Control of 3D Printed Pharmaceuticals using Process Analytical Technologies

Three-dimensional (3D) printing is forecast to cause a paradigm shift in pharmaceuticals, transitioning away from a ‘one-size-fits-all’ treatment approach towards personalised medicine. However, a major barrier to clinical integration lies in the inability to ensure the quality of the 3D printed tablets. Current quality control (QC) methods are inherently destructive, which would be unsuitable for the real-time release of printed medicines at the point-of-care. As such, this PhD thesis aims to evaluate the ability of process analytical technologies (PAT), including near infrared (NIR), Raman and terahertz spectroscopy, to act as alternative non-destructive QC methods for 3D printed medicines produced using selective laser sintering (SLS). The major findings were as follows: 1) NIR spectroscopy enabled the dose quantification of a single drug (paracetamol) and two distinct drugs (amlodipine and lisinopril) in a rapid, point-and-shoot process. Raman microscopy was found suitable to evaluate the drug distribution and solid-state characteristics across the dosage form surface and cross-section; 2) Amorphous solid dispersions of a BCS II drug (itraconazole) were produced using SLS 3D printing. Amorphous quantification was successful using NIR spectroscopy and Raman spectroscopy, which were comparable to reference x-ray powder diffraction (XRPD) analysis; 3) Laser scanning speed has a significant impact of 3D printed drug product density and drug release. Due to the different surface presentations of the dosage forms, preliminary data showed that FT-NIR spectroscopy may be a promising tool for the prediction of density and drug release. Overall, for the first time, this research demonstrates the potential for PAT technologies to undertake QC of 3D printed pharmaceuticals, overcoming a major barrier and hence supporting the integration of this technology into the clinic

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 290)

This bibliography lists 125 reports, articles and other documents introduced into the NASA scientific and technical information system in October 1986

UWOMJ Volume 40, Number 4, April 1970

Schulich School of Medicine & Dentistryhttps://ir.lib.uwo.ca/uwomj/1209/thumbnail.jp

Particle Size Determination during Fluid Bed Granulation : Tools for Enhanced Process Understanding

Fluid bed granulation (FBG) is a widely used process in pharmaceutical industry to improve the powder properties for tableting. During the granulation, primary particles are attached to each other and granules are formed. Since the physical characteristics (e.g. size) of the granules have a significant influence on the tableting process and hence on the end product quality, process understanding and control of the FBG process are of great importance. Process understanding can be created by exploiting the design of experiment studies in well instrumented FBG environment. In addition to the traditional process measurements and off-line analytics, modern process analytical technology (PAT) tools enable more relevant real-time process data acquisition during the FBG. The aim of this thesis was to study different particle size measurement techniques and PAT tools during the FBG in order to get a better insight into the granulation process and to evaluate possibilities for real-time particle size monitoring and control. Laser diffraction, spatial filtering technique (SFT), sieve analysis and new image analysis method (SAY-3D) were used as particle size determination techniques. In addition to the off-line measurement, SFT was also applied in-line and at-line, whereas SAY-3D was applied on-line. Modelling of the final particle size and the prediction of the particle size growth during the FBG was also tested using partial least squares (PLS). SFT studies revealed different process phenomena that could also be explained by the process measurement data. E.g., fine particles entrapment into the filter bags, blocking of the distributor plate and segregation in FBG were observed. The developed on-line cuvette enabled SAY-3D image acquisition and visual monitoring throughout the granulations and it performed well even in very wet conditions. Predictive PLS models for the final particle size could be constructed. Based on this information, pulsing of the granulation liquid feed was presented as a controlling tool to compensate for the excessive moisture content during the FBG. A new concept of utilising the process measurement data to predict particle size during FBG was also successfully developed. It was concluded that the new methods and PAT tools introduced and studied will enable enhanced process understanding and control of FBG process.Lääketeollisuuden valmistusprosesseja pyritään tehostamaan ja tuotteiden laatua parantamaan koko ajan. Perinteinen tapa on ollut, että lääkkeet testataan valmistuksen jälkeen ja varmistetaan, että niiden laatu vastaa asetettuja vaatimuksia. Nykyään pyrkimyksenä on kuitenkin se, että lääkevalmisteen laatu pystyttäisiin varmistamaan jo valmistuksen aikana, jolloin myös jälkikäteen tehtävää testausta voitaisiin keventää. Tätä varten tarvitaan kuitenkin uusia, nopeita ja lääketeollisuuden valmistusprosesseihin soveltuvia analyysitekniikoita. Tässä väitöstyössä tutkittiin leijupetirakeistusta, joka on keskeinen prosessi tablettivalmistukseen liittyen. Leijupetirakeistuksessa lääke- ja apuaineet sekoitetaan ja rakeistetaan, jonka jälkeen rakeista voidaan puristaa tabletteja. Rakeiden ominaisuudet vaikuttavat keskeisesti tabletointiprosessiin ja sitä kautta myös tablettien laatuominaisuuksiin. Yksi tärkeimpiä rakeiden ominaisuuksia on hiukkaskoko, jonka pitäisi olla asetetun tavoitteen mukainen ja sen tulisi olla mahdollisimman tasalaatuista eri valmistuserien välillä. Väitöstyössä tutkittiin mahdollisuuksia määrittää rakeiden hiukkaskoko leijupetiprosessin aikana ja siten hallita prosessia paremmin ja varmistaa rakeiden laatua jo valmistuksen aikana. Sekä kaupallisia hiukkaskoon määrityslaitteita että uusia kuva-analyysi- ja mallitusmenetelmiä tutkittiin. Tutkimusten avulla saatiin lisäymmärrystä leijupetirakeistuksen ilmiöistä ja löydettiin uusia tapoja seurata ja hallita rakeiden kasvua valmistuksen aikana. Väitöstyössä tutkittuja ja kehitettyjä hiukkaskoon määritysmenetelmiä on mahdollista hyödyntää uusien lääkkeiden tuotekehityksessä ja ne avaavat mahdollisuuksia myös lääkkeiden valmistusprosessin aikaiseen laadunvarmistukseen

Ceria-zirconia oxide high temperature desulfurization sorbent

High temperature desulfurization of highly reducing coal-derived gases using ceria and ceria-zirconia sorbents is the primary object of this dissertation research. If H2S concentration is reduced to less than 1 ppmv the product gas may be used with fuel cells and downstream catalytic process. CeO2 is reduced to a non-stoichiometric oxide, which is superior to CeO2 in removing H2S. Moreover, ZrO2 addition to CeO2 to form a solid solution, Ce1-xZrxO2, increases the reducibility of CeO2. This should also result in improved desulfurization performance. Pure CeO2 and sorbents, both commercially available and prepared at LSU, were tested. XRD analysis indicated that all sorbents containing ceria and zirconia formed a single phase. TGA analysis showed that overall reducibility of Ce1-xZrxO2 sorbents was better than pure CeO2. BET surface area measurements were also made to further characterize the sorbents. In the early stages of this research, commercially available sorbents were used for sulfidation tests. Experimental results were very promising. However, these commercially available sorbents were obtained from different sources and the differences in chemical and structural properties overwhelmed the possible effect of ZrO2 addition. Experimental results using LSU sorbents prepared using a coprecipitation method also produced favorable desulfurization results. H2S concentration in the product gas was reduced to less than 1 ppmv during the prebreakthrough phase of sulfidation tests with feed rates corresponding to about 3.8 second reactor residence time at temperatures in the range of 600 to 750oC. Addition of ZrO2 did not result in significant reduction of the H2S concentration during prebreakthrough, but did increase the duration of the prebreakthrough period. Addition of CO2, an oxygen source, to the feed gas decreased the prebreakthrough duration, but did not alter the sorbent’s ability to achieve sub-ppmv H2S concentrations level during prebreakthrough