Engineering particle agglomeration in dry powder inhaler. Paid master s thesis impact of carrier fine excipient. Pdf dry powder inhalers in copd, lung inflammation and. Welldesigned dry powder inhalers are highly efficient systems for pulmonary drug delivery. This thesis is divided in a general introduction, two major experimental parts and finally some remarks and perspectives. However, the powder fluidisation mechanisms are poorly understood which leads to low efficiency of dpis with 1035 % of the dose reaching the. Investigation of electrostatic charging phenomena in dry. This frequently involves the use of high amounts of excipients and. Pharm this thesis is submitted in fulfilment of the requirements for the degree of doctor of philosophy institute of health and biomedical innovation. These breathactivated devices have an advantage over metereddose inhalers because they do not require a patients coordination with drug actuation. Experimental and computational study of multiphase flow in.
Dry powder inhalers dpis are widely used for the therapy of respiratory and pulmonary diseases. Submitted in partial ful lment of the requirements for the award of doctor of philosophy of loughborough universit. The use of inverse gas chromatography for the study of. Novel dry powder inhalation system based on dispersion of lyophilisates core reader. Dry powder inhalers dpis are used to deliver locally acting drugs e. Preparation and in vitro evaluation of a polymer based controlled release dry powder inhaler formulation for pulmonary delivery.
Dry powder inhalers dpis are commonly used in the management of patients with copd. Pdf the pulmonary route is an interesting route for drug administration, both for effective local therapy asthma, chronic. The project is conducted in close cooperation with meggle, qualicaps, mg2 and university of parma. Appropriate use of inhaler devices such as metereddose inhalers mdis and drypowder inhalers dpis in clinical practice is not. Dry powder inhalers dpis are breath actuated devices relying on the inhalation effort generated by the patients during the inhalation manoeuvre to deaggregate and disperse the powder formulation and release the dose for lung deposition. The dpi formulation aims at pulmonary drug delivery. For design and development of the dry powder inhaler, we selected tobramycin as a model compound. Predicting the fine particle fraction of dry powder inhalers using.
During inhalation all dry powder inhalers require a forceto. The spraydrying parameters for generation of dry powders were optimised by using an inlet temperature of 120. Demcfd analysis of micromechanics for dry powder inhalers. Dpis are commonly used to treat respiratory diseases such as.
Towards the optimisation and adaptation of dry powder inhalers. Evaluating the effectiveness of written dry powder inhaler. University of groningen dry powder inhalation koning. Development of dry powder inhalers involves powder recrystallization, formulation, dispersion, delivery, and deposition of the therapeutic agent in different regions of the airways in prophylaxis treatment diagnosis of pulmonary and systemic disorders. Most dpi formulations consist of micronized drug blended with larger carrier particles. Pressurised metered dose inhalers, dry powder inhalers, inhalation characteristics, inhalation profiles, asthma, copd.
In one embodiment, the disperser acts both as a deagglomeration disintegration. Streptomycin was the first aminoglycoside isolated in 1943 from. American journal of respiratory and critical care medicine. Cfddem modeling of dry powder inhalers using micromodels a numerical and experimental study elly lucia gaggini emelie wasberg c elly lucia gaggini, emelie wasberg, 2018 masters thesis 2018. Dry powder inhalers dpis are a common therapeutic modality for lung diseases such as asthma, but they are also used to treat systemic diseases such as diabetes. In this study, a coupled discrete element method and computational fluid dynamics demcfd is employed to investigate the micromechanics of carrierbased dpis. A disperser for dry powders which can be used with different dose systems, dose weights ranging from 2 to 25 mg and different types of powder formulation. A thesis submitted in fulfilment of the requirements for the degree of doctor. Engineering nanoparticle agglomerates as dry powders for. Pharmaceutical aerosols are an effective method to deliver therapeutic agents to the respiratory tract. Dry powder inhalers dpis have great potential in pulmonary drug delivery. An alternative approach is to model fine particles using socalled micromodels. Another advantage of dpis is their breath activation, which makes them popular among patients. Dry powder inhalers for pulmonary drug delivery this is tfe1.
Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Modelling dry powder inhaler operation with the discrete. Tobramycin can be purchased either as free base or as sulphate. Computational modelling and optimization of dry powder. Malamatari thesis submitted in accordance with the requirements of ucl for the degree of doctor of philosophy july 2016 ucl school of pharmacy 2939. Development of spray dried liposomal dry powder inhaler of. Engineering particle agglomeration in dry powder inhaler formulations to co deliver drugs to the lungs. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. Technological and practical challenges of dry powder inhalation are explained and discussed and current developments and strategies for inhaled antibiotic drugs in tuberculosis therapy are critically evaluated. Masters thesis, royal college of surgeons in ireland. Only fine drug particles are emitted whereas the larger. Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory.
Dry powder inhalers dpi are one of the drug delivery systems available for delivery of pharmaceutics for the treatment of pulmonary diseases via lung. The most important parameters of powder for inhalation are the particle size, particle size distribution, morphology, crystallinity of the drug and dissolution rate buckton 1997, hickey et al. In chapter 1, a general introduction to inhalation therapy with dry powder inhalers is presented. Particle interactions in complex dry powder inhaled.
C, outlet temperature of 73 3c, aspirator rate of 100%, suspension feed rate of 11%, and spray flow rate of 600 lh using b290 buchi mini spraydryer. Chapter 3 dry powder inhalation of aminoglycosides or micin, respectively. In addition to the drug, the formulations often contain a coarse carrier, most commonly alpha lactose monohydrate. Development of dry powder inhalers involves powder recrystallization, formulation, dispersion, delivery, and deposition of the therapeutic agent in different regions of the airways in prophylaxis. Stability test of novel combined formulated dry powder inhalation. However, even with the best inhalation technique, only 1015 percent of the spray reaches the lungs. A dry powder inhaler dpi is a device that delivers medication to the lungs in the form of a dry powder. Cfddem modeling of dry powder inhalers using micromodels. However, there are still challenges when simulating dry powder inhalers with carrierbased drug formulations due to the large number of fine active drug particles.
Research paper the role of fines in the modification. Engineering nanoparticle agglomerates as dry powders for pulmonary drug delivery maria s. Dry powder inhalers dpis are well established as a means of delivering inhaled drugs to the lungs. Studies on the surface properties of biodegradable polymer. Dpis generate dry powder aerosols that deposit on the lung mucosa upon inhalation. Carrierfree highdose drypowder inhaler formulation of non. Given the importance of these characteristics to the performance of dry powder inhaler formulations dpis, it is unsurprising that igc has been applied to the study of these systems. Modelling dry powder inhaler operation with the discrete element method robert james tuley abstract dry powder inhalers dpi are a common asthma treatment. Dry powder inhalers dpi are an important drug delivery option, for the treatment of respiratory diseases, and, increasingly, for the delivery of systemically acting drugs and vaccines. Carrierfree highdose drypowder inhaler formulation of nonsteroidal antiinflammatory drugs.
Therefore, dpis are considered easier for patients to use. In passive dry powder inhalers dpis drug is often stored in blisters incorporated in the device. Demcfd analysis of micromechanics for dry powder inhalers by jiecheng yang a thesis submitted to the university of birmingham for the degree of doctor of philosophy school of chemical engineering university of birmingham april 2015. Proving the principal for commercial carrierbased dry powder inhalers, ddl23, edinburgh, uk. This thesis aims at the investigation of aspects concerning the formulation and the device in dry powder inhalation. The inhaled corticosteroids currently available in mdis are formulated in the traditional chlorfluorocarbon cfc propellants. Dpi delivers medication in the form of dry powder to lungs. University of szeged faculty of pharmacy department of. Expired lifetime application number ep02025796a other. Pdf development of dry powder inhalers researchgate. Ep1283036b1 multidosis dry powder inhaler with powder.
This investigation was undertaken to evaluate practical feasibility of site specific pulmonary delivery of liposomal encapsulated dapsone ds dry powder inhaler for prolonged drug retention in lungs as an effective alternative in prevention of pneumocystis carinii pneumonia pcp associated with immunocompromised patients. Demonstrating bioequivalence be for dpi products is challenging, primarily due to an incomplete understanding of the relevance of drug. Effect of lactose processing on dry powder inhaler dispersion. Assessing appropriate use of inhaler devices among. Improved aerosol deposition profiles from dry powder inhalers. Assessing appropriate use of inhaler devices among asthmatic patients by ola adel fawzi salah supervisor prof. The presence of fine lactose particles in the formulation is known to improve the formulation performance.
Welldesigned dry powder inhalers are highly efficient systems. Metered dose inhalers mdis are often preferred to other types of inhalation devices in the treatment of asthma, since they are compact, convenient and unobtrusive. I parisini, sj cheng, dd symons, mb brown, a kostrzewski, d murnane 2011, assessment of a cyclonetype spacer device for use in dry powder inhalation, ddl22, edinburgh, uk. Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from dry powder inhaler formulations rinku tuli b. For those dry powder inhalers that demonstrate significant flow dependent dosage. In vitro considerations to support bioequivalence of. The aim of this thesis is to study parameters that govern the. Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of. Experimental and computational study of multiphase ow in dry powder inhalers this item was submitted to loughborough universitys institutional repository by thean author. Part two of this thesis deals with aspects of prescribing and use of dry powder inhalers. The popularity of dry powder inhalers dpis to deliver drugs to the lungs is constantly increasing thanks to their advantages over nebulisers and pressurised metered dose inhalers pmdis, including the high stability of dry powders, avoidance of propellant gases and ease of use.
Invitro investigation of factors affecting the fate of. Novel dry powder inhalation system based on dispersion of. Dry powder inhalers dpis are used for delivering drugs to the airways. Flow simulations in twincaps dry powder inhaler using openfoam. Inverse gas chromatography igc is a sensitive technique for the measurement of powder surface properties, especially surface energetics. Drug delivery to the respiratory tract using dry powder inhalers. Dpis combine several advantages compared to metered dose inhalers mdis and other inhalation devices. Advantages of dpis include their portable design and low manufacturing costs. For dry powder inhalers, the user is required to generate a sufficient inspiratory flow to deagglomerate the particles for the inhaler to be effective. A wide range of dry powder inhaler devices are presently available in the market to deliver drugs with maximum drug delivery and low variability. Us6681768b2 powder formulation disintegrating system and. Experimental and computational study of multiphase ow in.
Preparation and in vitro evaluation of a polymer based. Is inhalation rate important for a dry powder inhaler. Pdf dry powder inhalers for pulmonary drug delivery. I parisini, sj cheng, dd symons, mb brown, a kostrzewski, d murnane 2011, assessment of a cyclonetype spacer device for use in. In this thesis the feasibility to treat bacterial infections effectively with inhaled dry powder antibiotics is explored. Drug delivery to the respiratory tract using dry powder inhalers thesis format. Integrated article by doaa mohamed ragab mossaad graduate program in chemical and biochemical engineering a thesis submitted in partial fulfillment of the requirements for the degree of doctor of philosophy the school of graduate and postdoctoral studies. Combination dpis, containing two or more drugs in a single.
Among aerosol generation systems, dry powder inhalers dpis have been an attractive technology for both local and systemic delivery of drugs. Dry powder inhalers in copd, lung inflammation and pulmonary infections article pdf available in expert opinion on drug delivery 126. The aerosol performance and physicochemical properties of. Glass beads as model carriers in dry powder inhalers. Despite the number of commercial devices available, little is known about their internal operation. Dpi is formulated either as a carrier based system or carrier free system. Quantification of the surface mo rphologies of lactose carriers and their effect on the in vitro deposition of salbutamol sulphate. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed. The aim was to study the stability of dry powder inhaler dpi.
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