Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance

The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, α-lactose monohydrate and D-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case

Message framing to inform cancer prevention pricing interventions in the UK and USA: a factorial experiment, 2019

Objectives: To advance understanding of how message framing can be used to maximise public support across different pricing policies for alcohol, tobacco and sugary drinks/foods that prevent consumption of cancer-causing products. Design: We designed a 3×4×3 randomised factorial experiment to test responses to messages with three pricing policies, four message frames and three products. Setting: Online survey panel (Qualtrics) in 2019. Participants: Adults (N=1850) from the UK and USA. Interventions: Participants randomly viewed one of 36 separate messages that varied by pricing policy (increasing taxes, getting rid of price discounts, getting rid of low-cost products), four frames and product (alcohol, tobacco, sugary drinks/foods). Primary and secondary outcome measures: We assessed the relationship between the message characteristics and four dependent variables. Three were related to policy support: (1) increasing taxes on the product mentioned in the message, (2) getting rid of price discounts and special offers on the product mentioned in the message and (3) getting rid of low-cost versions of the product mentioned in the message. One was related to reactance, a psychological response to having one’s freedom limited. Results: We found no effect for pricing policy in the message. Frames regarding children and reducing cancer risk moderated some outcomes, showing promise for real-world use. We found differences in support by product and reactance with greatest support and least reactance for tobacco policies, less support and more reactance for alcohol policies, and the least support and most reactance for sugary drinks/foods policies. Conclusions: Cancer prevention efforts using policy interventions can be informed by the message framing literature. Our results offer insights for cancer prevention advocacy efforts across the UK and USA and highlight that tax versus non-tax approaches to increasing the cost of cancer-causing products result in similar responses from consumers

Autism associated with tetrasomy 15: A further report

Association of autism with tetrasomy of chromosome 15 has recently been described in six males. In this report, we describe the occurrence of autism in a girl with tetrasomy of chromosome 15. The patient showed hyperactivity, hand-flapping, short-stature, eye abnormalities, and hypotonia, which have been reported in males with tetrasomy of chromosome 15. This suggests that autism may be associated in both sexes with a distinct syndrome characterized by tetrasomy of chromosome 15, mental retardation and characteristic physical features. L'association d'autisme avec une tétrasomie du chromosome 15 a été décrite récemment chez six garçons. Dans cet article, nous décrivons la survenue d'un autisme chez une fille avec une tétrasomie du chromosome 15. La patiente présentait une hyperactivité, un battement des mains, une petite taille, des anormalités des yeux et une hypotonie qui ont été rapportées chez des garçons avec tétrasomie du chromosome 15. Ceci suggère que l'autisme peut être associé dans les deux sexes avec un syndrome distinct caractérisé par une tétrasomie du chromosome 15, un retard mental et des traits physiques caractéristiques. Kürzlich wurde eine Assoziation einer Tetrasomie des Chromosoms 15 mit Autismus bei 6 männlichen Individuen beschrieben. In dem vorliegenden Fallbericht wird das Vorkommen eines Autismus bei einem Mädchen mit einer Tetrasomie des Chromosoms 15 dargestellt. Die Patientin zeigte Hyperaktivität, Handstereotypien, ophthalmologische Auffälligkeiten und Hypotonie. Diese Auffälligkeiten sind auch bei den männlichen Individuen mit einer Tetrasomie 15 beschrieben worden. Diese Befunde legen nahe, daß bei beiden Geschlechtern Autismus mit einem eigenständigen Syndrom im Falle des Vorliegens einer Tetrasomie 15 einhergeht, dessen wesentliche Merkmale geistige Behinderung und charakteristische Auffälligkeiten sind.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41756/1/787_2005_Article_BF02098582.pd

Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC

The determination of chemical purity, melting range, and variation of enthalpy in the process of characterizing medicines is one of the principal requirements evaluated in quality control of the pharmaceutical industry. In this study, the method of purity determination using DSC was outlined, as well as the application of this technique for the evaluation of commercial samples of zidovudine (AZT) (raw material) supplied by different laboratories. To this end, samples from six different laboratories (A, B, C, D, E, and F) and the standard reference (R) from the United States Pharmacopeia (USP) were analyzed. The DSC curves were obtained in the temperature range of 25 to 200 ºC under the dynamic atmosphere of N2 (50 mL min-1), heating rate of β=2 ºC min-1, using an Al capsule containing approximately 2 mg of sample material. The results demonstrated that the standard reference presented a proportion of 99.83% whereas the AZT samples presented a variation ranging from 97.59 to 99.54%. In addition, the standard reference was found to present a temperature of onset of melting point of 122.80 °C. Regarding the samples of active agents provided by the different laboratories, a variation ranging from 118.70 to 122.87 °C was measured. In terms of ΔHm, the samples presented an average value of 31.12 kJ mol-1._________________________________________________________________________________________ RESUMO: A determinação da pureza química, a faixa de fusão e a variação de entalpia envolvida no processo de caracterização de fármacos é um dos principais requisitos avaliados no controle de qualidade em indústrias farmacêuticas. Neste trabalho é feita uma breve abordagem sobre o método de determinação de pureza utilizando DSC, assim como a aplicação desta técnica para avaliação de amostras comerciais de zidovudina (AZT) (matéria-prima) fornecida por diferentes laboratórios. Para tal, foram analisadas amostras de seis diferentes laboratórios (A,B,C,D,E e F) e a substância química de referência (R) da United States Pharmacopeia (USP). As curvas DSC foram obtidas na faixa de temperatura entre 25 a 200 ºC, sob atmosfera dinâmica de N2 (50 mL min-1), β=2 ºC min-1, utilizando cápsula de Al contendo aproximadamente 2 mg de amostra. De acordo com os resultados, pode-se observar que a substância química de referência apresentou teor igual a 99,83% e que as amostras de AZT apresentaram uma faixa de variação entre 97,59 e 99,54%. Pode-se verificar, ainda, que a substância química de referência apresentou uma temperatura onset de fusão igual a 122,80 °C. Para as amostras dos princípios ativos fornecidos pelos diferentes laboratórios, pode-se verificar uma faixa de variação entre 118,70 e 122,87 °C. No que se refere ao ΔHm, as amostras apresentaram valor médio de 31,12 kJ.mol-1