Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI) for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI) with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction

Measurements of the Proton and Deuteron Spin Structure Functions g1g_{1} and g2g_{2}

Measurements are reported of the proton and deuteron spin structure functions g1 at beam energies of 29.1, 16.2, and 9.7 GeV and g2 at a beam energy of 29.1 GeV. The integrals of g1 over x have been evaluated at fixed Q**2 = 3 (GeV/c)**2 using the full data set. The Q**2 dependence of the ratio g1/F1 was studied and found to be small for Q**2 > 1 (GeV/c)**2. Within experimental precision the g2 data are well-described by the Wandzura-Wilczek twist-2 contribution. Twist-3 matrix elements were extracted and compared to theoretical predictions. The asymmetry A2 was measured and found to be significantly smaller than the positivity limit for both proton and deuteron targets. A2 for the proton is found to be positive and inconsistent with zero. Measurements of g1 in the resonance region show strong variations with x and Q**2, consistent with resonant amplitudes extracted from unpolarized data. These data allow us to study the Q**2 dependence of the first moments of g1 below the scaling region

Impact of lack of knowledge on risk perception and protective practices of home nurses handling antineoplastic drugs

Introduction Health care workers handling antineoplastic drugs (ADs) are at risk of carcinogenic, mutagenic and reproductive toxic risks (CMR). The aim of this study was to assess the impact of the lack of knowledge (K) on risk perception (P) and on protective practices (PP) related to the handling of home-based chemotherapy (HC) by home nurses. Methods This study was conducted in Normandy among home nurses. A questionnaire was developed to explore the K, P and PP related to handling ADs by home nurses working with four different providers from two hospitals. Results Among the 28 home nurses included, 25.93% had received initial training on the specific treatment of ADs, 48.15% scored below average on risk management K, 52.00% scored below average on personal PP. Conclusion This study reveals the importance of adapted and regular training on the handling of ADs. It will help develop a climate of safety and reinforce adherence to wearing personal protective equipment to protect health care workers from contamination

Management de la qualité du circuit des produits de santé expérimentaux dans les pharmacies hospitalières : enquête nationale et développement d’outils standardisés

Objectives. - Carry out a national inventory of the current situation regarding the quality management of the investigational health products circuit, to develop adapted standardised tools. Methods. - A survey of 76 questions, developed by a regional working group, was conducted among clinical research pharmacists in French facilities. Tools were developed to meet the identified needs and validated by participating pharmacists, using the Delphi method. The consensus was defined by achieving a score above 80% on relevance, clarity and evaluability.Results. - Among 94 pharmacists participating in the survey, 88 were interested in standardised tools. The score for the implementation of a quality approach depended on the type of health facility (P < 0.0005) and increased with the number of active trials (P < 0.0005). All nine proposed tools were useful for over two thirds of pharmacists, but the self-assessment and audit grids have been prioritised. Indeed, only 26% of pharmacies carried out a prior risk assessment and 14% carried out internal audits. The review of both grids led to a consensus on 89% and 97% of the criteria respectively. The validated grids include 62 and 72 criteria respectively.Discussion. - The quality approach of the investigational health products circuit is heteroge-neous in the participating centres, with a strong need for standardised tools. The two grids are relevant tools developed by and for professionals.Conclusion. - The tools developed will enable to optimise the quality approach by identifying the non-conformities of the investigational health products circuit.(c) 2021 Academie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved

Impact of low- and high-risk operators handling irinotecan on the blood contamination of health care workers in oncology day care units

Introduction Health care workers handling antineoplastic drugs (ADs) are at risk of mutagenicity and adverse reproductive effects. Despite protective equipment and AD handling guidelines, AD levels are still detected in caregivers in oncology units. This study attempted to assess blood contamination by irinotecan and its metabolites in all health care workers in oncology day hospital units according to activities specific to each employment category. Methods The study was performed at two different hospitals: a university hospital and a comprehensive cancer centre. Forty-four participants were categorized according to their daily activity as a high-risk operator (29 nurses/ward aides and 5 cleaning staff) and a low-risk operator (7 doctors and 3 secretaries). The collected blood samples were subjected to UHPLC-MS/MS. The plasma and red blood cell (RBC) levels of irinotecan and its metabolites (SN-38; APC) were determined using a validated analytical method detection test. Results Two hundred sixty-four assay results were collected (132 plasma results and 132 RBC results). The comparison between low- and high-risk operator-contaminated workers was not significant (18.33% positive results in low-risk operators vs. 25.98% positive results in high-risk operators; P = 0.22). This homogeneity showed overall contamination within the unit. Positive results were obtained in 21.43% of physicians, 11.11% of secretaries, 25.86% of nurses/ward aides and 26.67% of cleaning staff. These results could be explained by the lack or failure of personal and collective protective equipment. A lack of protection and inadequate decontamination procedures can result in surface contamination. Conclusions This study evaluated blood contamination with irinotecan and its metabolites in health care workers from day hospital care units. Among the 24.24% of contaminations observed in care units, the difference between low- and high-risk operator contamination was not significant (P = 0.22). The impact on blood contamination found is the same between low- and high-risk caregivers. This implies that the protective precautions associated with the handling of anticancer drugs must therefore be followed by all staff, including those believed to be at low risk of exposure

Does equipment change impact blood contamination with irinotecan and its two major metabolites in a centralized cytotoxic pharmacy unit?

International audienceBackground Antineoplastic drugs exposure is a major problem for caregivers’ health. The aim of this study is to assess blood contamination with irinotecan and its two metabolites in a centralized pharmacy unit for cytotoxic drug preparations workers before and after protective equipment changes. Methods The study took place in a university hospital centralized pharmacy unit for cytotoxic drug and was performed in two parts, before (Round 1: R1) and after equipment changes (Round 2: R2). Collection of pharmacy staff blood samples was performed in UHPLC-MS/MS. Plasma and red blood cell irinotecan and its metabolites (SN38; APC) were determined with a validated analytical method detection test. Results A total of 15/36 (41.6%) assays were positive in R1 and 16/72 (22.2%) in R2 with a significant decrease between periods ( P = 0.035). For plasma dosages, no difference between the two periods was found ( P = 0.71); respectively 4/18 (22.2%) assays were positive in R1 and 6/36 (16.6%) in R2. For red blood cells dosages, a significant decrease between periods was found ( P = 0.01); respectively 11/18 (61%) were positive in R1 and 10/36 (27.8%) in R2. Conclusions These dosages make it possible to have the very first evaluation for plasma and red blood cell contamination with irinotecan and its metabolites in the context of equipment changes, both at individual and collective levels. This work would help to protect health workers from the potential risks represented by these molecules, especially by revealing a contamination of workers in order to objectify the results of exposure

Effect of a prospective audit with intervention and feedback on Clostridioides difficile infection management

International audienceBackground Clostridioides difcile infections are associated with morbidity and mortality in several countries. Their increasing incidence and frequent recurrence make them an urgent public health threat. The lack of adherence to international treatment guidelines for Clostridioides difcile infections is a proven mortality risk factor. Objective To evaluate long-term prescribers’ adherence to recommendations on the management of Clostridioides difcile infections and its impact on clinical outcomes after an educational and Clostridioides difcile-prospective audit with intervention and feedback period. Setting All patients admitted to a 1500-bed university hospital with positive Clostridioides difcile tests identifed were included. Methods Data were collected retrospectively over a baseline period (May–November 2014) and prospectively over a Clostridioides difcile-prospective audit with intervention and feedback period (November 2015–May 2016) and an observation period (November 2017–September 2018). All Clostridioides difcile cases were reviewed by a Clostridioides difcile-prospective audit with intervention and feedback team composed of pharmacists, an infectious diseases specialist and a microbiologist to obtain a complete overview of patient records in each area of expertise. Main outcome measures Percentage of conformity to the protocol, percentage of recovery at 10 days and percentage of relapse, as well as Clostridioides difcile incidence and percentage of Fidaxomicin use. Results A total of 183 patients were included over the three periods. A signifcant improvement in conformity to the local protocol was observed between the intervention period (23.9%) and the observation period (67.3%) (P<10–3). Fidaxomicin prescriptions increased signifcantly (P=0.006). Clinical outcomes improved signifcantly with an increase in the percentage of recovery at 10 days (P=0.001) and a decrease in the percentage of relapse (P=0.016). The Clostridioides difcile incidence rate improved signifcantly to 1.3 per 10,000 patient-days during the observation period. Conclusion This study shows the lasting efect of an educational and Clostridioides difcile-prospective audit with intervention and feedback period on prescribers’ adherence to recommendations and a signifcant impact on clinical outcomes

Perception, knowledge, and handling practice regarding the risk of exposure to antineoplastic drugs in oncology day hospitalization units and compounding unit staff.

International audienceBackgroundAntineoplastic drug exposure is a major problem in regard to caregivers’ health. The aim of the present study was to assess the perception, knowledge, and handling practices of all occupation level categories of two oncology day hospitalization units and two compounding units regarding the risk of exposure to antineoplastic drugs.MethodsThis descriptive study, performed through face-to-face interviews, concurrently assessed the perception, knowledge, and handling practices of antineoplastic drugs in five different job categories in four different settings. This work was part of a larger comprehensive project examining surface and blood contamination. Different scores were assigned to evaluate responses to a questionnaire about the perception, knowledge, and handling practices of healthcare workers, a risk global score including a risk perception score, and education/knowledge and handling practices scores.ResultsIn the survey, continuous training was associated with the global risk score (p = 0.03), particularly with the handling practices risk score (p = 0.01). Job category was also significantly associated with the global risk score (p < 0.001), particularly with the handling practices risk score (p < 0.001) and the education/knowledge score (p < 0.001). Pharmacy technicians had the highest score regarding risk perception (71.4%), indicating a higher perception of risk, and had a lower score regarding handling practices (25.0%) as well as a lower score (15.7%) regarding risk knowledge. Nurses and physicians had a high score (50%) regarding the risk of handling practices and a score of 57.1% regarding risk perception, indicating an increased perception of safety. Auxiliary caregivers had the highest global score (43.5%) and a score of 30.0% regarding handling practices.ConclusionsThis study identified significant differences among healthcare workers depending on job categories in the antineoplastic drug handling practices and in the knowledge of the risks associated with occupational exposure to antineoplastic drugs. These differences were particularly important between trained and untrained participants, revealing the importance of implementing a continuous training program

Towards a more desirable dry powder inhaler formulation: large spray-dried mannitol microspheres outperform small microspheres

Purpose: To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. Methods: Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid-state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance. Results: All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM. Conclusion: Particle shape and solid-state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study. © 2013 Springer Science+Business Media New York