83 research outputs found
Evaluation of a nanodispersion formulation prepared through microfluidic reactors for pulmonary delivery of budesonide using nebulizers
This study aimed to determine the aerosolization behavior of a nanodispersion of budesonide, prepared using microfluidic reactors. The size and morphology of budesonide nanoparticles were characterized by photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM). Processing/formulation parameters for formation of the nanoparticles were studied to determine their effects on the particle size. Results showed a narrow distribution for budesonide nanodispersion with spherical and smooth surfaced particles. To investigate the in-vitro aerosolization performance of the nanodispersion, the preparation was compared with a commercially available budesonide microsuspension using the ComitĂ© EuropĂ©en Normalization (CEN) methodology. Aerosolization results showed that the fine particle fraction (FPF) generated from the budesonide nanodispersion was significantly higher than that of the marketed budesonide (ie. mean (SD) 56.88 (3.37) vs. 38.04 (7.82), respectively). Additionally, mass median aerodynamic diameter (MMAD) of nano-budesonide dispersion was significantly smaller than the microsuspension (ie. mean (SD) 3.91 (0.49) vs. 6.22 (1.09) ĂÂŒm, respectively), with nebulization time of nano-budesonide dispersion significantly shorter than the marketed budesonide microsuspension (ie. 12.3 (0.37) vs. 14.85 (0.36) min, respectively). The produced nanodispersion was found to be stable over a period of 10 days if stored at 4 Ă°C. Ă© 2014 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services
Performance evaluation of two Raman instruments for unknown forensic samples
The Misuse of Drugs Act 1971 classifies Class A, B and C drugs as illegal and over 30000 Class A seizures were reported in England and Wales in 2013/14.1 The drug substance is typically formulated with an array of cutting agents, e.g. Benzocaine, Lidocaine and Phenacetin, leading to a complex mixture of organic species. Early attempts to automate identification of such materials were hampered by spectral overlap and interference. However, developments in computational deconvolution of a spectral data has led to the development of systems that potentially identify targeted components in complex mixtures.2 In this work, a Handheld Raman instrument (Thermo-TruNarc), incorporating an implementation of such an algorithms, was tested with an array of seized samples from UK forensic investigation. These âstreetâ samples were unmodified from seizure and presented as powders (43 samples) and oil (1 sample). The spectral output of the Handheld system was compared with spectra from a laboratory micro-Raman instrument obtained from at least three sites in each sample. Spectra from the laboratory system were assigned and the results compared to the identification reported from the portable system. In 39/44 of cases a valid identification was obtained although, of these, 12 required a sample treatment with an ethanol extraction followed by evaporation onto a proprietary SERS substrate (âTest-Stickâ analysis). A detailed evaluation of spectral features was undertaken for all cases and where assignments were inconclusive after direct sampling these were mainly attributed to sample fluorescence. Hence, the TruNarc system was shown to be reliable and capable of identifying complex street sample and such identification are available to users with the minimum of spectroscopic expertise
Impact of Mixed Solvent on Co-Crystal Solubility, Ternary Phase Diagram, and Crystallization Scale Up
This contribution covers the identification, understanding, and rationale of the interplay between the choice of mixed solvent on the crystallization of the co-crystal system benzoic acid and isonicotinamide (BZ:INA). A critical first step was gauging the impact of solvent choice and composition on the overall crystallization process, across a number of temperature points. This required defining the solubility and phase diagrams of the co-crystal system at specified temperatures, which reflects the cooling by crystallization profile encountered in a batch crystallization step. To this end,
identifying and understanding the impact of solvent composition over a selected temperature range on the solubility of co-crystal underpins this contribution
Characterization and Biocompatibility Study of Nematic and Cholesteryl Liquid Crystals.
noIntensive research in bio-engineering has been conducted in the search for flexible biomaterials that could support cell growth and cells attachment. Flexible synthetic materials that support cell growth without the aid of synthetic extracellular matrix proteins are still rare. Cholesteryl liquid crystal containing cholesteryl moieties may have suitable biological affinity. Human keratinocytes (HaCat) were cultured with a nematic liquid crystal and three cholesteryl liquid crystals of different formulation. Subsequently, the trypan blue dye exclusion assay was used to determine cell viability in the liquid crystals. The two classes of liquid crystal were characterized by Differential Scanning Calorimeter (DSC) and polarizing microscope (POM) to understand the nature of the interface material. The cell viability study in medium containing liquid crystals verified that liquid crystals had no effects on cell viability. However, only the surface of cholesteryl liquid crystal has shown affinity to HaCat cells. In addition, cells continued to proliferate in the presence of liquid crystals without a change of medium for eight days. No sign of exothermic and endothermic activities at 370C were observed from the DSC test results for the three samples. Biological and mechanical test result of the cholesteryl liquid crystals has shown that cholesteryl liquid crystals are non toxic and support cell attachment without extracellular matrix protein at very low elasticity
Rational Development of a Carrier-Free Dry Powder Inhalation Formulation for Respiratory Viral Infections via Quality by Design: A Drug-Drug Cocrystal of Favipiravir and Theophylline
Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique
niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral
drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility.
An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-
by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing
a 1:1 favipiravirâtheophylline (FAV-THP) cocrystal via spray drying, which may provide
an alternative treatment strategy for individuals with concomitant influenza infections and chronic
obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal Xray
diffraction, powder X-ray diffraction, and the construction of a temperatureâcomposition phase
diagram. A three-factor, two-level, full factorial design was employed to produce the optimized
formulation and study the impact of critical processing parameters on the resulting median mass
aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried
FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a
smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93
ÎŒm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in
A549 cells
âThe People Who Leave Here Are Not the People Who Arrived.â: A Qualitative Analysis of the Therapeutic Process and Identity Transition in the Offender Personality Disorder Pathway
Individuals with personality disorder are often construed as difficult to treat, and sometimes even âuntreatable.â In this study, 24 men who had completed treatment on the offender personality disorder treatment pathway participated in focus groups at a high-security prison in the United Kingdom. The results of the data analysis revealed three superordinate themes that captured the impact and experience of the therapeutic process. The three themes were âA self-reconstructed,â which focused on the reconstruing and reconstructions of participantsâ identity and how intervention assisted with a coherent narrative of self. The second superordinate theme, âRelational resilience and dealing with abandonment,â relates to the attachment to therapists and the negotiation of relational boundaries and resilience. The third theme, âReimagining and re-experiencing trauma,â focuses on participantsâ exploration and reliving of trauma, and how group processes allowed for shared understanding and a reconstruing of their trauma. Implications for policy and practice are discussed
First Comparative Study of the Three Polymorphs of Bis(isonicotinamide) Citric Acid Cocrystals and the Concomitant Salt 4âCarbamoylpyridinium Citrate Isonicotinamide
This contribution presents a previously unreported
example and comparative study of a binary
crystalline adduct that exhibits concomitant salt and cocrystal
forms. Specifically, three new polymorphs (α, ÎČ, Îł) of a novel
2:1 cocrystal of bis(isonicotinamide) citric acid are reported,
and the route to isolating each polymorph from aqueous
solution is presented and the crystal chemistry of the system is
characterized. In addition, the metastable 2:1 salt (ionic
adduct) isolated as a transient (overlapping) phase under
crystallization conditions identical to the polymorphs is also
presented. As far as the authors can ascertain, this may be the
first reported example of a saltâcocrystalâpolymorphic
concomitant system. A comparative study of the solid form
landscape is presented, wherein mapping reveals the unique structural complexity of this multiple form saltâcocrystal
concomitant system. The α and ÎČ forms are structurally very similar, where comparisons of packing behavior are shown to only
be different outside the glide plane. The Îł form is very different in structure, where supramolecular chirality is present. In
addition, further characterization of the isolated solid-state forms includes thermal, spectroscopic, and computational analysis,
all of which are employed to further verify the solid form landscape of the isonicotinamideâcitric acid adduct and were found to
have an order of stability of ÎČ, α, Îł, salt, the salt being the metastable form
First steps for the direct purification of L-Leu-L-Leu dipeptide through co-crystallisation
Trifluoroacetate salt contamination of peptides represents a challenging issue related to solid phase peptide synthesis and purification because it affects the chemical and biological properties of peptides. Purification of such materials is typically performed through a two-step post-synthetic procedure based on chromatography followed by ion exchange. For the first time, co-crystallization is presented in this study as a possible alternative and advantageous single-step method for the obtaining of TFA-free crystals of a dipeptide. A trifluoroacetate-contaminated L-Leu-L-Leu dipeptide has been used for co-crystallization experiments along with different solid coformers. New multicomponent crystals containing only the title compound and the second co-crystal formers are described in this work. Such results represent a novelty in the field of peptide chemistry and a valid proof for the use of crystal engineering-based method for a combined purification and crystallization strategy
Using Drug Development Methodology to Improve Survivorship and Supportive Care Intervention Trials.
This is the peer reviewed version of the following article: Howells, L., Hulbert-Williams, N. J. & Blagden, S. P. (2019). Using drug development methodology to improve survivorship and supportive care intervention trials (Invited Editorial). Psycho-Oncology, 28(7), which has been published in final form at https://doi.org/10.1002/pon.5100. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingN/
"A different world" exploring and understanding the climate of a recently re-rolled sexual offender prison
Understanding how sexual offenders experience prison and its environment is important because such experiences can impact on rehabilitation outcomes. The purpose of this research investigation was to explore the rehabilitative and therapeutic climate of a recently re-rolled sexual offender prison. The research took a mixed methods approach and consisted of quantitative and qualitative phases. There were differences between prisoners and staff on their perception of the prison climate and for prisoner and staff relationships. The qualitative results helped to explain the quantitative findings and added a more nuanced understanding of the experience of the prison, the nature of prisoner and staff relationships and the opportunities for personal growth within the prison. The study has important implications for prisons that co-locate sexual offenders and want to provide an environment conducive to rehabilitation
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