Potential of a cyclone prototype spacer to improve in vitro dry powder delivery

Copyright The Author(s) 2013. This article is published with open access at Springerlink.com. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedPurpose: Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrierbased DPIs was investigated. Methods: Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30-60 Lmin-1. Deposition of particles in the next generation impactor and within the devices was determined by high performance liquid chromatography. Results: Reduced induction port deposition of the emitted particles from the cyclones was observed due to the high retention of the drug within the spacers (e.g. salbutamol sulphate (SS): 67.89 ± 6.51 % at 30 Lmin-1 in Cheng 1). Fine particle fractions of aerosol as emitted from the cyclones were substantially higher than the DPIs alone. Moreover, the aerodynamic diameters of particles emitted from the cyclones were halved compared to the DPIs alone (e.g. SS from the Cyclohaler® at 4 kPa: 1.08 ± 0.05 μm vs. 3.00 ± 0.12 μm, with and without Cheng 2, respectively) and unaltered with increased flow rates. Conclusion: This work has shown the potential of employing a cyclone spacer for commercial carrier-based DPIs to improve inhaled drug delivery.Peer reviewe

Performance Characteristics of Breezhaler((R)) and Aerolizer((R)) in the Real-World Setting

The evaluation of errors in use with different inhaler devices is challenging to quantify as there are a number of definitions of critical and non-critical errors with respect to inhaler use; in addition, performance characteristics of the device, such as airflow resistance, can also influence effective use in the real-world setting. Repeated observations and checking/correcting inhaler use are essential to optimise clinical effectiveness of inhaled therapy in patients. Breezhaler® is a single unit-dose dry powder inhaler used in chronic obstructive pulmonary disease and in asthma (budesonide) that has low airflow resistance, making it easier for patients of varying disease severities to achieve the inhalation flow rate required for lung deposition of treatment. Similar to Breezhaler®, the Aerolizer® is a single unit-dose dry powder inhaler used in asthma management with low airflow resistance. Studies have shown relatively low rates of critical errors with Breezhaler® and Aerolizer®, with similarities in the critical errors reported; these data on critical errors together with similarities in the usability of Breezhaler® and Aerolizer® further support the functional similarity between the two devices in both asthma and chronic obstructive pulmonary disease. Breezhaler® also has patient-feedback features, including use of a transparent drug capsule that can be checked after inhalation to see it is empty. The low resistance of the dose-confirming Breezhaler® results in less inspiratory effort being required by patients for its effective use, which allows the device to be used effectively across a wide age range of patients and disease severities

Certolizumab effect in a cohort of 60 Libyan patients with rheumatic diseases

Background: Tumour Necrosis Factor (TNF) has a central role in the pathogenesis of Rheumatoid Arthritis (RA), mediating both inflammation and joint damage. Certolizumab Pegol (CZP) is a PEGylated Fab fragment of a humanized anti-TNF antibody with high affinity to TNF.Objective: The study was done to monitor the effects and side effects of certolizumab on our Libyan patients with rheumatic diseases.Methods: The inclusion criteria for the study were all patients with rheumatic diseases who were treated by certolizumab in the period from August 2014 to August 2016 in Rheumatology Department, Tripoli Medical Center, Tripoli, Libya. They were 60 patients, 43 of them had RA, 14 patients had Ankylosing Spondylitis (AS), 2 patients had Psoriatic Arthropathy (PsA) and 1 patient had enteropathic arthritis. Certolizumab 400mg subcutaneous was given at week 0, 2, 4 and then 400mg every 4 weeks. Demographic details such as age and sex were recorded. Clinical characteristics as rheumatoid factor in RA patients, disease duration, duration of taking certolizumab and drugs used before starting certolizumab were noted. Assessment of disease activity was measured by DAS28 for RA patients, by BASDAI for AS patients and by DAPsA for PsA patients. For all patients, complete blood count, erythrocyte sedimentation rate, liver function test, hepatitis screen, urine routine examination and tuberculin test before starting certolizumab were requested to monitor its side effects during follow up.Results: Forty three patients had rheumatoid arthritis, their mean age was 44.6±SD10.67 years, 11.6% were male and 88.3% were female. Rheumatoid factor was positive in 58%, negative in 19% and unknown in 23%. Fourteen patients were ankylosing spondylitis; their mean age was 34.9±SD8.22 years, 85.7% were male and 14.2% were female. Two patients had psoriatic arthritis, mean age was 43.5±SD16.26 years, one was female and the other was male. One patient had enteropathic arthritis; she was a female aged 57 years. All RA patients were on prednisolone and/or one or two DMARD before starting CZP and failed to show response. All AS patients were on one or two NSAIDs and/or salazopyrine and failed to show response before starting CZP. One psoriatic arthritis patient was on leflunomide and methotrexate (MTX) and the other was on MTX alone. Enteropathic arthritis patient was on MTX, azathioprine and salazopyrine. The mean of DAS28 before starting CZP for RA patients was 4.9+SD1.15 and the mean of DAS28 at the last dose was 3.1±SD1.12 (P value<0.0001). The mean of BASDAI before using CZP was 4.2±SD1.61 and the mean of BASDAI at the last dose was 1.7±SD1.86 (P value <0.0012). Both PsA patients had moderate disease activity (mean of DAPsA=20±SD1.6) and became (mean of DAPsA=6±SD1.2) which means low disease activity (P value <0.0002). Enteropathic arthritis patients showed significant improvement regarding gastrointestinal symptoms and arthritis. Regarding side effects of certolizumab pegol, one female RA patient developed tuberculus lymphadenitis and one male RA patient had hypersensitivity reaction.Conclusion: During two years of follow up of our rheumatic diseased patients on certolizumab, we noticed a significant improvement in disease activity scores with minimal side effects

High Performance Liquid Chromatography Assay Method for Simultaneous Quantitation of Formoterol and Budesonide in Symbicort Turbuhaler

NoA sensitive and rapid high performance liquid chromatography method has been developed and used for the simultaneous determination of formoterol and budesonide in Symbicort Turbuhaler when assessing the aerodynamic characteristics of the emitted dose using Pharmacopoeial methods. This capability results in both time and cost saving. The mobile phase composition was acetonitrile-5 mM sodium dihydrogen orthophosphate, pH 3 (60: 40% v/v), and was passed at 1.5 ml min-1 through a C18 column with a UV detection (wavelength 214 nm). The method was shown to give good analytical performance in terms of linearity, precision (using phenylpropanolamine as an internal standard), sensitivity and solution stability. The intra-day precision for both formoterol and budesonide were 0.75% and 1.11%, respectively (n = 10). The limit of quantitation for formoterol was 10 ¿g L-1 and for budesonide was 120 ¿g L-1, and the limit of detection were 3 and 30 ¿g L-1, for both formoterol and budesonide, respectively. The method has been applied to determine the content of the emitted dose and the fine particle dose of Symbicort Turbuhaler

Health related Quality of Life in Libyan patients with rheumatoid arthritis

Background: In order to measure therapeutic effects or assess disease course, outcome measurement parameters are commonly used in patients with Rheumatoid Arthritis (RA). Quality of Life (QoL) is important outcome measure. There is a paucity of data on the impact of chronic rheumatic diseases on functional disability, as well as Health-Related Quality of Life (HRQOL) in Africans (1). Unfortunately there is no available data about HRQOL in Libya. Objective: Evaluation of RA burden in Libya was the aim of the study; the study goal was to determine Health Related Quality Of Life (HRQOL) in patients with Rheumatoid Arthritis (RA), who are on disease modifying antirheumatic drugs (DMARD). Setting: Rheumatology clinic of Tripoli Medical Center, Tripoli, Libya. Methods: The inclusion criteria for the study were all patients who were diagnosed to have RA by the American College of Rheumatology ACR criteria of 1987, were on DMARDs (started within 6 months of disease duration), had a 28-joint disease activity score (DAS28) of 2.6-5.1, attended the rheumatology clinic of Tripoli Medical Center, Tripoli, Libya, from 1st June 2010 to 30th July 2010 and consented to participate in the study. The study was done after receiving consent from the Tripoli Medical Center ethical and research committee. Results: One hundred patients were included in the study. The age at diagnosis ranged from 15 to 73 years; the median age was 39 years. The majority of patients were females 94 (94%) patients and 6 (6%) patients were male. The disease duration (symptoms onset to evaluation) ranged from 6 months to 40 years, the median disease duration was 7 years. Rheumatoid factor was positive in 72 (72%) patients. They had a 28-joint disease activity score (DAS28) of 2.6-5.1. They were on DMARDs started within 6 months of disease duration, 85% were on methotrexate, 10% were on hydroxychloroquine and 5% were on sulfasalazine. Sixty five percent were on prednisolone tablets (5mg) in addition to DMARDs. Sixty three percent of patients had score 0-1, 25% of them had score 1-2 and 12% had score 2-3. The mean of HAQ score for all patients was 0.86 with standard deviation (SD) of 0.76. The median was 0.75 (range 0.000-2.625). Conclusion: After evaluation of the RA burden in Libya, we found that 63% of our patients had HAQ score of 0-1, which means mild to moderate disability. In this study, patients selected were using DMARDs at early stage of the disease, (disease duration 6 months), in further studies, we will compare these results with results of patients who had used DMARDs at later stage of the disease