The development of a testing procedure for dry friction brakes

A description of the background to testing friction materials for automotive brakes explains the need for a rapid, inexpensive means of assessing their behaviour in a way which is both accurate and meaningful. Various methods of controlling inertia dynamometers to simulate road vehicles are rejected in favour of programming by means of a commercially available XY plotter. Investigation of brake service conditions is used to set up test schedules, and a dynamometer programming unit built to enable service conditions on vehicles to be simulated on a full scale dynamometer. A technique is developed by which accelerated testing can be achieved without operating under overload conditions, saving time and cost without sacrificing validity. The development of programming by XY plotter is described, with a method of operating one XY plotter to programme the machine, monitor its own behaviour, and plot its own results in logical sequence. Commissioning trials are described and the generation of reproducible results in frictional behaviour and material durability is discussed. Teclmiques are developed to cross check the operation of the machine in retrospect, and retrospectively correct results in the event of malfunctions. Sensitivity errors in the measuring circuits are displayed between calibrations, whilst leaving the recorded results almost unaffected by error. Typical results of brake lining tests are used to demonstrate the range of performance parameters which can be studied by use of the machine. Successful test investigations completed on the machine are reported, including comments on behaviour of cast iron drums and discs. The machine shows that materials can repeat their complex friction/ temperature/speed/pressure relationships at a reproducibility of the order of +-0.003u and +~ 0.0002 in. thickness loss during wear tests. Discussion of practical and academic implications completes the report with recommendations for further work in both fields.

Characterisation and surface-profiling techniques for composite particles produced by dry powder coating in pharmaceutical drug delivery

The production of composite particles using dry powder coating is a one-step, environmentally friendly, process for the fabrication of particles with targeted properties and favourable functionalities. Diverse functionalities, such flowability enhancement, content uniformity, and dissolution, can be developed from dry particle coating. In this review, we discuss the particle functionalities that can be tailored and the selection of characterisation techniques relevant to understanding their molecular basis. We address key features in the powder blend sampling process and explore the relevant characterisation techniques, focussing on the functionality delivered by dry coating and on surface profiling that explores the dynamics and surface characteristics of the composite blends. Dry particle coating is a solvent- and heat-free process that can be used to develop functionalised particles. However, assessment of the resultant functionality requires careful selection of sensitive analytical techniques that can distinguish particle surface changes within nano and/or micrometre ranges.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

Dry powder inhalation of macromolecules using novel PEG-co-polyester microparticle carriers

This study investigated optimizing the formulation parameters for encapsulation of a model mucinolytic enzyme, a-chymotrypsin (a-CH), within a novel polymer; poly(ethylene glycol)-co-poly(glycerol adipate-co-?-pentadecalactone), PEG-co-(PGA-co-PDL) which were then applied to the formulation of DNase I. a-CH or DNase I loaded microparticles were prepared via spray drying from double emulsion (w(1)/o/w(2)) utilizing chloroform (CHF) as the organic solvent, l-leucine as a dispersibility enhancer and an internal aqueous phase (w(1)) containing PEG4500 or Pluronic(®) F-68 (PLF68). a-CH released from microparticles was investigated for bioactivity using the azocasein assay and the mucinolytic activity was assessed utilizing the degradation of mucin suspension assay. The chemical structure of PEG-co-(PGA-co-PDL) was characterized by (1)H NMR and FT-IR with both analyses confirming PEG incorporated into the polymer backbone, and any unreacted units removed. Optimum formulation a-CH-CHF/PLF68, 1% produced the highest bioactivity, enzyme encapsulation (20.08±3.91%), loading (22.31±4.34µg/mg), FPF (fine particle fraction) (37.63±0.97%); FPD (fine particle dose) (179.88±9.43µg), MMAD (mass median aerodynamic diameter) (2.95±1.61µm), and the mucinolytic activity was equal to the native non-encapsulated enzyme up to 5h. DNase I-CHF/PLF68, 1% resulted in enzyme encapsulation (17.44±3.11%), loading (19.31±3.27µg/mg) and activity (81.9±2.7%). The results indicate PEG-co-(PGA-co-PDL) can be considered as a potential biodegradable polymer carrier for dry powder inhalation of macromolecules for treatment of local pulmonary diseases.

The predictive ability of clinical tests for contact lens induced dry eye

Approximately half of current contact lens wearers suffer from dryness and discomfort, particularly towards the end of the day. Contact lens practitioners have a number of dry eye tests available to help them to predict which of their patients may be at risk of contact lens drop out and advise them accordingly. This thesis set out to rationalize them to see if any are of more diagnostic significance than others. This doctorate has found: (1) The Keratograph, a device which permits an automated, examiner independent technique for measuring non invasive tear break up time (NITBUT) measured NITBUT consistently shorter than measurements recorded with the Tearscope. When measuring central corneal curvature the spherical equivalent power of the cornea was measured as being significantly flatter than with a validated automated keratometer. (2) Non-invasive and invasive tear break-up times significantly correlated to each other, but not the other tear metrics. Symptomology, assessed using the OSDI questionnaire, correlated more with those tests indicating possible damage to the ocular surface (including LWE, LIPCOF and conjunctival staining) than with tests of either tear volume or stability. Cluster analysis showed some statistically significant groups of patients with different sign and symptom profiles. The largest cluster demonstrated poor tear quality with both non-invasive and invasive tests, low tear volume and more symptoms. (3) Care should be taken in fitting patients new to contact lenses if they have a NITBUT less than 10s or an OSDI comfort rating greater than 4.2 as they are more likely to drop-out within the first 6 months. Cluster analysis was not found to be beneficial in predicting which patients will succeed with lenses and which will not. A combination of the OSDI questionnaire and a NITBUT measurement was most useful both in diagnosing dry eye and in predicting contact lens drop out.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.

Report of the inaugural meeting of the TFOS i2 = initiating innovation Series:targeting the unmet need for dry eye treatment

On March 21, 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i2 = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i2 meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i2 meeting.

Management of allergic conjunctivitis and dry eye

Ocular allergy is a common eye condition encountered in clinical practice. However, little is known how seasonal allergic conjunctivitis (SAC), the most common subtype, is managed in clinical practice. Further, dry eye, another common eye condition, may be misdiagnosed as SAC and vice-versa as they share similar signs and symptoms. In addition, despite the frequent recommendation of non-pharmacological treatments for SAC, evidenceto support their use has not been identified in the scientific literature. The aim of this thesis was therefore to determine the actual diagnosis and management of SAC and dry eye in clinical practice and investigate the efficacy of non-pharmacological treatments for these conditions. The diagnostic and management strategies for SAC and dry eye employed by pharmacy staff are found to be inconsistent with current guidelines and scientific evidence based upon a mystery shopper design. Cluster analysis of tear film metrics in normal and dry eye patients identified several clinically relevant groups of patients that may allow for targeted treatment recommendations. Using a novel environmental chamber model of SAC, the use of artificial tears and cold compresses, either alone or combined is an effective treatment modality for acute and symptomatic SAC, on a par with topical anti-allergic medication, and has been demonstrated for the first time. In addition, eyelid warming therapy with a simple, readily available, seed filled device is an effective method of treating meibomian gland dysfunction (MGD) related evaporative dry eye, perhaps the most common dry eye subtype. A greater focus on ophthalmology must be implemented as part of the formal education and training of pharmacy staff, while greater professional communication between community pharmacists, optometrists and the population they serve is required. Artificial tears and cold compresses may be considered as front line agents for acute SAC by pharmacy staff and optometrists, to whom pharmacological treatment options are limited.

Chitosan-modified dry powder formulations for pulmonary gene delivery

Spray-drying is an effective process for preparing micron-dimensioned particles for pulmonary delivery. Previously, we have demonstrated enhanced dispersibility and fine particle fraction of spray-dried nonviral gene delivery formulations using amino acids or absorption enhancers as dispersibility-enhancing excipients. In this study, we investigate the use of the cationic polymer chitosan as a readily available and biocompatible dispersibility enhancer. Lactose-lipid:polycation:pDNA (LPD) powders were prepared by spray-drying and post-mixed with chitosan or spray-dried chitosan. In addition, the water-soluble chitosan derivative, trimethyl chitosan, was added to the lactose-LPD formulation before spray-drying. Spray-dried chitosan particles, displaying an irregular surface morphology and diameter of less than 2 mu m, readily adsorbed to lactose-LPD particles following mixing. In contrast with the smooth spherical surface of lactose-LPD particles, spray-dried trimethyl chitosan-lactose-LPD particles demonstrated increased surface roughness and a unimodal particle size distribution (mean diameter 3.4 mu m), compared with the multimodal distribution for unmodified lactose-LPD powders (mean diameter 23.7 mu m). The emitted dose and in vitro deposition of chitosan-modified powders was significantly greater than that of unmodified powders. Moreover, the inclusion of chitosan mediated an enhanced level of reporter gene expression. In summary, chitosan enhances the dispersibility and in vitro pulmonary deposition performance of spray-dried powders.

Randomised masked clinical trial of the MGDRx eyebag for the treatment of meibomian gland dysfunction-related evaporative dry eye

Background/aims To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. Methods Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, noninvasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. Results Differences between test and control eyes at baseline were not statistically signi ficant for all measurements ( p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes ( p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months ( p<0.05), although the bene fit was greater in those who continued usage 1-8 times a month (p<0.001). Conclusions The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. Trial registration number NCT01870180.

Management of dry eye in UK pharmacies

Purpose - To investigate the ability of pharmacy staff in the United Kingdom (UK) to diagnose and treat dry eye. Methods - A mystery shopper technique to simulate a patient with presumed dry eye was used in 50 pharmacy practices in major towns and cities across the UK. Pharmacies were unaware of their involvement in the study. With the exception of a predetermined opening statement to initiate the consultation, no further information was volunteered. Questions asked, diagnoses given, management strategy advised and staff type was recorded immediately after the consultation. Results - The mean number of questions was 4.5 (SD 1.7; range 1–10). The most common question was the duration of symptoms (56%) and the least common was whether the patient had a history of headaches (2%). All pharmacy staff gave a diagnosis, but the majority were incorrect (58%), with only 42% correctly identifying dry eye. Treatment was advised by 92% of pharmacy staff, with the remaining 8% advising referral directly to the patient's GP or optometrist. Dry eye treatments involved topical ocular lubrication via eye drops (90%) and lipid based sprays (10%). However, only 10% gave administration advice, 10% gave dosage advice, 9% asked about contact lens wear, and none offered follow up although 15% also advised GP or optometrist referral. Conclusions - There is a need for improved ophthalmological training amongst pharmacists and pharmacy staff and establishment of cross referral relationships between pharmacies and optometry practices.

What is the optimum artificial treament for dry eye?

Dry eye disease is a common clinical condition whose aetiology and management challenges clinicians and researchers alike. Practitioners have a number of dry eye tests available to clinically assess dry eye disease, in order to treat their patients effectively and successfully. This thesis set out to determine the most relevant and successful key tests for dry eye disease diagnosis/ management. There has been very little research on determining the most effective treatment options for these patients; therefore a randomised controlled study was conducted in order to see how different artificial treatments perform compared to each other, whether the preferred treatment could have been predicted from their ocular clinical assessment, and if the preferred treatment subjectively related to the greatest improvement in ocular physiology and tear film stability. This research has found: 1. From the plethora of ocular the tear tests available to utilise in clinical practice, the tear stability tests as measured by the non-invasive tear break (NITBUT) up time and invasive tear break up time (NaFL TBUT) are strongly correlated. The tear volume tests are also related as measured by the phenol red thread (PRT) and tear meniscus height (TMH). Lid Parallel Conjunctival Folds (LIPCOF) and conjunctival staining are significantly correlated to one another. Symptomology and osmolarity were also found to be important tests in order to assess for dry eye. 2. Artificial tear supplements do work for ocular comfort, as well as the ocular surface as observed by conjunctival staining and the reduction LIPCOF. There is no strong evidence of one type of artificial tear supplement being more effective than others, and the data suggest that these improvements are more due to the time than the specific drops. 3. When trying to predict patient preference for artificial tears from baseline measurements, the individual category of artificial tear supplements appeared to have an improvement in at least 1 tear metric. Undoubtedly, from the study the patients preferred artificial tear supplements’ were rated much higher than the other three drops used in the study and their subjective responses were statistically significant than the signs. 4. Patients are also willing to pay for a community dry eye service in their area of £17. In conclusion, the dry eye tests conducted in the study correlate with one another and with the symptoms reported by the patient. Artificial tears do make a difference objectively as well as subjectively. There is no optimum artificial treatment for dry eye, however regular consistent use of artificial eye drops will improve the ocular surface.

Functionalised particles using dry powder coating in pharmaceutical drug delivery:promises and challenges

Introduction: Production of functionalised particles using dry powder coating is a one-step, environmentally friendly process that paves the way for the development of particles with targeted properties and diverse functionalities. Areas covered: Applying the first principles in physical science for powders, fine guest particles can be homogeneously dispersed over the surface of larger host particles to develop functionalised particles. Multiple functionalities can be modified including: flowability, dispersibility, fluidisation, homogeneity, content uniformity and dissolution profile. The current publication seeks to understand the fundamental underpinning principles and science governing dry coating process, evaluate key technologies developed to produce functionalised particles along with outlining their advantages, limitations and applications and discusses in detail the resultant functionalities and their applications. Expert opinion: Dry particle coating is a promising solvent-free manufacturing technology to produce particles with targeted functionalities. Progress within this area requires the development of continuous processing devices that can overcome challenges encountered with current technologies such as heat generation and particle attrition. Growth within this field requires extensive research to further understand the impact of process design and material properties on resultant functionalities.

Change of composition and diversity of species and grassland management between different grazing intensity in Pannonian dry and wet grasslands

Investigations were carried out in wet and dry pasture. Coenological recordings were taken in three zones. The first zone (“A”) located 0-50 m near the stable, second zone (“B”) located 50-150 m from the stable, while the third zone (“C”) located farther than 150 m. We have carried out analyses of ecological and environmental factors and life form types. Based on our results for both dry and wet grasslands, quadrates of “A” zone were well isolated from the rest of the zones. Overgrazing, which involves considerable trampling, vanishes differences among vegetations, thereby promotes weed and disturbance tolerant rich vegetation. The lowest species number and diversity could be found here. Due to the nitrogen enrichment due to the constant presence of livestock, drier and less heat demanding habitat developed in the “A” zones, according to the environmental indicators. Because of the change in management, conservation and diversity values of “C” zone increased, however, according to nature protection values it underperformed compared to “B” zone. According to the sample area, wet grasslands from the sandy areas of Kiskunság, preserve nature protection values and grass composition better moving away from stables, due to less grazing pressure. Drier backgrounds tolerate stronger grazing pressure.