Quantification and Control of Cohesive and Adhesive Forces in Dry Powder Inhaler Formulations

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mathematical approach for understanding deagglomeration behaviour of drug powder in formulations with coarse carrier

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Deagglomeration of cohesive particles in combination with coarse carrier is a key requirement for inhaled formulations. The aim of the project was to propose a mathematical approach to understand aerosolization behaviour of micronized particles alone and in formulation with carriers. Salbutamol sulphate and salmeterol xinafoate were blended separately with fine lactose (ratio 1:4) and fine and coarse lactose (1:4:63.5). Laser diffraction was employed to characterize the powder median particle size. The deagglomeration of micronized materials followed an asymptotic monoexponential relationship. When the coarse lactose was added, the relationship fitted a bi-exponential equation showing an easily and a poorly dispersed fraction. Using model hydrophobic and hydrophilic APIs, this study has demonstrated the utility of an analytical approach that can parameterize deagglomeration behaviour of carrier-free and carrier-based inhalation formulations. The analytical approach provides the ability to systematically study the effect of material, formulation and processing factors on deagglomeration behaviour.Peer reviewe

Influence of excipients on spray-dried powders for inhalation

Two areas attracting considerable attention when developing effective pulmonary drug delivery systems include the improvement of aerosolisation efficiency of the inhaled formulation and the controlled release of drug from the formulation following deposition within the lung. In this study, four saccharides were employed as excipients in the preparation of spray-dried powder formulations for the pulmonary drug delivery. Beta-cyclodextrin-, starch-, and sodium carboxymethylcellulose (NaCMC)-based spray-dried powders showed a significant (one-way ANOVA, Duncan's test, p < 0.05) increase in lower stage drug deposition in the Next Generation Impactor (NGI) when compared to lactose-based spray-dried powders. Furthermore, NaCMC-based spray-dried powder formulations exhibited a sustained drug release profile in dissolution testing; approximately 80% of salbutamol sulphate was released after an hour, whereas drug from the lactose-based spray-dried powder formulation was released within 5 min. Our results clearly demonstrate that the inclusion of NaCMC in spray-dried powder formulations increases the aerosolisation efficiency of the powder and also offers the potential for sustained drug release, which may be of benefit in the treatment of local and systemic conditions

From single excipients to dual excipient platforms in dry powder inhaler products

AbstractRecent years have seen a marked diversification of excipient based formulation strategies used for the development and commercialisation of dry powder inhaler (DPI) products. These innovative approaches not only provide benefits to patients and health care professionals through the availability of a wider range of therapeutic DPI products, but, importantly, also allow formulators to exploit the potential opportunities that excipients provide for the development of DPIs. Whilst many DPI products have, and continue to be developed using a single formulation excipient, the commercialisation of DPI products which contain the two excipients lactose monohydrate and magnesium stearate, namely the ‘dual excipient platform’ has recently been achieved. This article provides an overview of the background and current status of the development of such ‘dual excipient platform’ based DPI products

Numerical Analysis of the Effect of Particle Shape and Adhesion on the Segregation of Powder Mixtures

Segregation of granules is an undesired phenomenon in which particles in a mixture separate from each other based on the differences in their physical and chemical properties. It is, therefore, crucial to control the homogeneity of the system by applying appropriate techniques. This requires a fundamental understanding of the underlying mechanisms. In this study, the effect of particle shape and cohesion has been analysed. As a model system prone to segregation, a ternary mixture of particles representing the common ingredients of home washing powders, namely, spray dried detergent powders, tetraacetylethylenediamine, and enzyme placebo (as the minor ingredient) during heap formation is modelled numerically by the Discrete Element Method (DEM) with an aim to investigate the effect of cohesion/adhesion of the minor components on segregation quality. Non-spherical particle shapes are created in DEM using the clumped-sphere method based on their X-ray tomograms. Experimentally, inter particle adhesion is generated by coating the minor ingredient (enzyme placebo) with Polyethylene Glycol 400 (PEG 400). The JKR theory is used to model the cohesion/adhesion of coated enzyme placebo particles in the simulation. Tests are carried out experimentally and simulated numerically by mixing the placebo particles (uncoated and coated) with the other ingredients and pouring them in a test box. The simulation and experimental results are compared qualitatively and quantitatively. It is found that coating the minor ingredient in the mixture reduces segregation significantly while the change in flowability of the system is negligible

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

Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations

Spray-drying allows to modify the physicochemical/mechanical properties of particles along with their morphology. In the present study, L-leucine with varying concentrations (0.1, 0.5, 1, 5, and 10% w/v) were incorporated into lactose monohydrate solution for spray-drying to enhance the aerosolization performance of dry powder inhalers containing spray-dried lactose-leucine and salbutamol sulfate. The prepared spray-dried lactose-leucine carriers were analyzed using laser diffraction (particle size), differential scanning calorimetry (thermal behavior), scanning electron microscopy (morphology), powder X-ray diffraction (crystallinity), Fourier transform infrared spectroscopy (interaction at molecular level), and in vitro aerosolization performance (deposition). The results showed that the efficacy of salbutamol sulfate’s aerosolization performance was, in part, due to the introduction of L-leucine in the carrier, prior to being spray-dried, accounting for an increase in the fine particle fraction (FPF) of salbutamol sulfate from spray-dried lactose-leucine (0.5% leucine) in comparison to all other carriers. It was shown that all of the spray-dried carriers were spherical in their morphology with some agglomerates and contained a mixture of amorphous, α-lactose, and β-lactose. It was also interesting to note that spray-dried lactose-leucine particles were agglomerated during the spray-drying process to make coarse particles (volume mean diameter of 79 to 87 μm) suitable as a carrier in DPI formulations

Supply-related drivers of staff motivation for providing intermittent preventive treatment of malaria during pregnancy in Tanzania: evidence from two rural districts

BACKGROUND: Since its introduction in the national antenatal care (ANC) system in Tanzania in 2001, little evidence is documented regarding the motivation and performance of health workers (HWs) in the provision of intermittent preventive treatment of malaria during pregnancy (IPTp) services in the national ANC clinics and the implications such motivation and performance might have had on HWs and services' compliance with the recommended IPTp delivery guidelines. This paper describes the supply-related drivers of motivation and performance of HWs in administering IPTp doses among other ANC services delivered in public and private health facilities (HFs) in Tanzania, using a case study of Mkuranga and Mufindi districts. METHODS: Interviews were conducted with 78 HWs participating in the delivery of ANC services in private and public HFs and were supplemented by personal communications with the members of the district council health management team. The research instrument used in the data collection process contained a mixture of closed and open-ended questions. Some of the open-ended questions had to be coded in the form that allowed their analysis quantitatively. RESULTS: In both districts, respondents acknowledged IPTp as an essential intervention, but expressed dissatisfaction with their working environments constraining their performance, including health facility (HF) unit understaffing; unsystematic and unfriendly supervision by CHMT members; limited opportunities for HW career development; and poor (HF) infrastructure and staff houses. Data also suggest that poor working conditions negatively affect health workers' motivation to perform for ANC (including IPTp) services. Similarities and differences were noted in terms of motivational factors for ANC service delivery between the HWs employed in private HFs and those in public HFs: those in private facilities were more comfortable with staff residential houses, HF buildings, equipment, availability of water, electricity and cups for clients to use while taking doses under direct observed therapy than their public facility counterparts. Employees in public HFs more acknowledged availability of clinical officers, nurses and midwives than their private facility counterparts. More results are presented and discussed. CONCLUSION: The study shows conditions related to staffing levels, health infrastructure and essential supplies being among the key determinants or drivers of frontline HWs' motivation to deliver ANC services in both private and public HFs. Efforts of the government to meet the maternal health related Millennium Development Goals and targets for specific interventions need to address challenges related to HWs' motivation to perform their duties at their work-places

A qualitative study of nursing student experiences of clinical practice

BACKGROUND: Nursing student's experiences of their clinical practice provide greater insight to develop an effective clinical teaching strategy in nursing education. The main objective of this study was to investigate student nurses' experience about their clinical practice. METHODS: Focus groups were used to obtain students' opinion and experiences about their clinical practice. 90 baccalaureate nursing students at Shiraz University of Medical Sciences (Faculty of Nursing and Midwifery) were selected randomly from two hundred students and were arranged in 9 groups of ten students. To analyze the data the method used to code and categories focus group data were adapted from approaches to qualitative data analysis. RESULTS: Four themes emerged from the focus group data. From the students' point of view," initial clinical anxiety", "theory-practice gap"," clinical supervision", professional role", were considered as important factors in clinical experience. CONCLUSION: The result of this study showed that nursing students were not satisfied with the clinical component of their education. They experienced anxiety as a result of feeling incompetent and lack of professional nursing skills and knowledge to take care of various patients in the clinical setting