Developing Dry Powder Inhaler Formulations.

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology versus affordability in the evolving inhaler market.

Scale resolving simulations of the effect of glottis motion and the laryngeal jet on flow dynamics during respiration.

BACKGROUND AND OBJECTIVE: The movement of the respiratory walls has a significant impact on airflow through the respiratory tract. The majority of computational fluid dynamics (CFD) studies assume a static geometry which may not provide a realistic flow field. Furthermore, many studies use Reynolds Averaged Navier-Stokes (RANS) turbulence models that do not resolve turbulence structure. Combining the application of advanced scale-resolving turbulence models with moving respiratory walls using CFD will provide detailed insights into respiratory flow structures. METHODS: This study simulated a complete breathing cycle involving inhalation and exhalation in a nasal cavity to trachea geometry that incorporated moving glottis walls. A second breathing cycle was simulated with static glottis walls for comparison. A recently developed hybrid RANS-LES turbulence model, the Stress-Blended Eddy Simulation (SBES), was incorporated to resolve turbulent flow structures in fine detail for both transient simulations. Transient results were compared with steady-state RANS simulations for the same respiratory geometry. RESULTS: Glottis motion caused substantial effects on flow structure through the complete breathing cycle. Significant flow structure and velocity variations were observed due to glottal motion, primarily in the larynx and trachea. Resolved turbulence structures using SBES showed an intense mixing section in the glottis region during inhalation and in the nasopharynx during expiration, which was not present in the RANS simulations. CONCLUSION: Transient simulations of a realistic breathing cycle uncovered flow structures absent in simulations with a constant flow rate. Furthermore, the incorporation of glottis motion impacted airflow characteristics that suggest rigid respiratory walls do not accurately describe respiratory flow. Future research in respiratory airflow should be conducted using transient scale-resolving models in conjunction with moving respiratory walls to capture flow structures in detail.

The perfect storm: temporal analysis of air during the world's most deadly epidemic thunderstorm asthma (ETSA) event in Melbourne.

BACKGROUND: There have been 26 epidemic thunderstorm asthma (ETSA) events worldwide, with Melbourne at the epicentre of ETSA with 7 recorded events, and in 2016 experienced the deadliest ETSA event ever recorded. Health services and emergency departments were overwhelmed with thousands requiring medical care for acute asthma and 10 people died. OBJECTIVES: This multidisciplinary study was conducted across various health and science departments with the aim of improving our collective understanding of the mechanism behind ETSA. DESIGN: This study involved time-resolved analysis of atmospheric sampling of the air for pollen and fungal spores, and intact and ruptured pollen compared with different weather parameters, pollution levels and clinical asthma presentations. METHODS: Time-resolved pollen and fungal spore data collected by Deakin AirWATCH Burwood, underwent 3-h analysis, to better reflect the 'before', 'during' and 'after' ETSA time points, on the days leading up to and following the Melbourne 2016 event. Linear correlations were conducted with atmospheric pollution data provided by the Environment Protection Authority (EPA) of Victoria, weather data sourced from Bureau of Meteorology (BOM) and clinical asthma presentation data from the Victorian Agency for Health Information (VAHI) of Department of Health. RESULTS: Counts of ruptured grass pollen grains increased 250% when the thunderstorm outflow reached Burwood. Increased PM10, high relative humidity, decreased temperature and low ozone concentrations observed in the storm outflow were correlated with increased levels of ruptured grass pollen. In particular, high ozone levels observed 6 h prior to this ETSA event may be a critical early indicator of impending ETSA event, since high ozone levels have been linked to increasing pollen allergen content and reducing pollen integrity, which may in turn contribute to enhanced pollen rupture. CONCLUSION: The findings presented in this article highlight the importance of including ruptured pollen and time-resolved analysis to forecast ETSA events and thus save lives.

Bulk Flow Optimisation of Amorphous Solid Dispersion Excipient Powders through Surface Modification.

Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their bulk flow and affects their utility and viability in terms of powder production, processing, and function. This study explores the effectiveness of L-leucine (L-leu) coprocessing in modifying the particle surface of ASD-forming materials. Various contrasting prototype coprocessed ASD excipients from both the food and pharmaceutical industries were examined for their effective coformulation with L-leu. The model/prototype materials included maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). The spray-drying conditions were set such that the particle size difference was minimised, so that it did not play a substantial role in influencing powder cohesion. Scanning electron microscopy was used to evaluate the morphology of each formulation. A combination of previously reported morphological progression typical of L-leu surface modification and previously unreported physical characteristics was observed. The bulk characteristics of these powders were assessed using a powder rheometer to evaluate their flowability under confined and unconfined stresses, flow rate sensitivities, and compactability. The data showed a general improvement in maltodextrin, PVP K10, trehalose and gum arabic flowability measures as L-leu concentrations increased. In contrast, PVP K90 and HPMC formulations experienced unique challenges that provided insight into the mechanistic behaviour of L-leu. Therefore, this study recommends further investigations into the interplay between L-leu and the physico-chemical properties of coformulated excipients in future amorphous powder design. This also revealed the need to enhance bulk characterisation tools to unpack the multifactorial impact of L-leu surface modification.

"I really liked the chance to talk about it": Students' Reflections on the Process of Completing Paper Puzzles, a Novel Active Learning Activity.

Introduction: Research shows active learning is an effective teaching method. However, few qualitative studies explore medical student perceptions of the active learning process. The present study explored what students thought about while completing paper puzzles, an active learning tool used at the University of Utah School of Medicine, to understand what and how medical students think while engaged in active learning. Materials and Methods: To investigate second-year medical students' attitudes toward these active learning exercises, three Zoom-based focused groups were held and recorded throughout the course. Recordings were transcribed and coded using thematic analysis. Results: Students reported that peer interactions were of high value, and that while some interactions and thought processes were action-oriented, others were more metacognitive. Other benefits of the activity included promotion of learning, provision of structure, and designation of high-yield concepts. Challenges included feelings of confusion, problems with timing or difficulty of the tasks, and low utility without adequate preparation. Discussion: These findings reflect student-acknowledged pros and cons of active learning described in education literature and add further insight into the thoughts and conversations students have during active learning activities. These include practicing metacognitive skills, triaging information, and learning from peers. Conclusions: These data further elucidate student perceptions of active learning activities in medical education. Though focused on a specific activity, the data can help medical educators understand what students appreciate about active learning and what they think about while engaged in such activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01682-y.

Assessment for Learning with Ungraded and Graded Assessments.

Introduction: Assessment for learning has many benefits, but learners will still encounter high-stakes decisions about their performance throughout training. It is unknown if assessment for learning can be promoted with a combination model where scores from some assessments are factored into course grades and scores from other assessments are not used for course grading. Methods: At the University of Utah School of Medicine, year 1-2 medical students (MS) completed multiple-choice question quiz assessments and final examinations in six systems-based science courses. Quiz and final examination performance counted toward course grades for MS2017-MS2018. Starting with the MS2020 cohort, quizzes no longer counted toward course grades. Quiz, final examination, and Step 1 scores were compared between ungraded quiz and graded quiz cohorts with independent samples t-tests. Student and faculty feedback was collected. Results: Quiz performance was not different for the ungraded and graded cohorts (p = 0.173). Ungraded cohorts scored 4% higher on final examinations than graded cohorts (p ≤ 0.001, d = 0.88). Ungraded cohorts scored above the national average and 11 points higher on Step 1 compared to graded cohorts, who had scored below the national average (p ≤ 0.001, d = 0.64). During the study period, Step 1 scores increased by 2 points nationally. Student feedback was positive, and faculty felt it improved their relationship with students. Discussion: The change to ungraded quizzes did not negatively affect final examination or Step 1 performance, suggesting a combination of ungraded and graded assessments can effectively promote assessment for learning.

Highlighting DEM's Potential to Gauge Mechanistic Attributes of MUPS Tablet and Capsule Formulations.

Simulation of pharmaceutical unit operations by the discrete element method (DEM) has elevated our understanding of the impact of single-particle interactions on themselves, and on the entire tablets/powder. Studies in the past have shown how this knowledge helps to mitigate/solve multiple challenges during conventional formulation and process development/modernization/troubleshooting, with minimal use of active drug material. This communication adds to this- highlighting the tool's potential for a rapid preliminary assessment of the mechanistic attributes of multiple unit particle system (MUPS) based tablet and capsule drug products.

Distal nerve transfer for thenar palsy: A cadaveric study.

INTRODUCTION: Severe proximal median nerve palsies often result in irreversible thenar atrophy and thumb abduction function loss. Tendon transfer involves substantial limitations and challenges; but, distal nerve transfer may provide an alternative treatment. Our goal was to validate the anatomical suitability of two distal ulnar nerve branches for thenar muscle reanimation. MATERIALS AND METHODS: We assessed nerve transfer to the recurrent branch of median nerve (RMN) in 16 embalmed cadaveric hands. The ulnar motor branch to the flexor digiti minimi brevis (FDMBn) and the ulnar motor branch to the third lumbrical (3rdLn) were assessed for transfer. Coaptation success was measured by the overlap of the nerve donor with the RMN and correspondence of nerve diameters. RESULTS: The mean transferable length and width of the RMN were 20.7 ± 4.5 and 1.0 ± 0.3 mm, respectively. We identified an average of three branches in the branching anatomy from the ulnar nerve to the hypothenar muscles. The maximal transferable lengths and widths of the FDMBn and the 3rdLn were 13.8 ± 4.4 and 0.5 ± 0.1 mm and 24.1 ± 6.4 and 0.4 ± 0.1 mm, respectively. The overlap with the RMN of the FDMBn and 3rdLn was 9.0 ± 3.6 (2.0-15.3) and 17.8 ± 6.0 (4.7-27.5) mm, respectively. CONCLUSIONS: This anatomical study demonstrates the feasibility of distal nerve transfers between the ulnar and median nerves in the hand for reanimation of thenar muscles. Ulnar motor donors of the BrFDMBn and 3rdLn likely represent the least morbid donors with short distances for regeneration and a single coaptation repair.

Who is the Teacher and Who is the Student? The Dual Service- and Engaged-Learning Pedagogical Model of Anatomy Academy.

Anatomy Academy is a simultaneous service-learning experience for preprofessional school undergraduate students and preclinical professional students acting as classroom paraprofessional teachers (Mentors), and engaged-learning experience for fourth to sixth grade elementary school children (Students). Using didactic and kinesthetic active learning teaching strategies in small-group classroom environments, Mentors taught anatomy, physiology, and nutrition concepts to Students. In this study of the program's early years (2012-2014), overall objectives of improving Mentors' pedagogical confidence; and Students' science interest, science knowledge, and exercise self-efficacy were assessed. Mentors showed (89% response of 595 surveyed) improvement in content delivery (P < .001), student engagement (P < .001), classroom management (P < .001), and professionalism (P = .0001). Postprogram Mentor reflections were categorized into 7 major themes that demonstrated personal growth through the service-learning opportunity: (1) realization of an ability to make a difference in the world now; (2) acknowledgment of the importance of listening in teaching; (3) recognition that lives can and will change with "a little love"; (4) insight into the effectiveness of guiding Students through material rather than lecturing; (5) awareness of the value of respect in the learning environment; (6) cognizance of the power of individualized attention to motivate Students; and (7) reflection of one's own personal growth through the open influence of Students. Students showed (88% response of 1259 surveyed) improvement in science knowledge (P = .014) and exercise self-efficacy (P = .038), but not science interest (P = .371). Thus, while Students are learning more science and becoming more aware of their health, we need to be more overt in our presence as scientists in the educational arena.

To Protect and to Preserve: Novel Preservation Strategies for Extracellular Vesicles.

Extracellular vesicles (EVs)-based therapeutics are based on the premise that EVs shed by stem cells exert similar therapeutic effects and these have been proposed as an alternative to cell therapies. EV-mediated delivery is an effective and efficient system of cell-to-cell communication which can confer therapeutic benefits to their target cells. EVs have been shown to promote tissue repair and regeneration in various animal models such as, wound healing, cardiac ischemia, diabetes, lung fibrosis, kidney injury, and many others. Given the unique attributes of EVs, considerable thought must be given to the preservation, formulation and cold chain strategies in order to effectively translate exciting preclinical observations to clinical and commercial success. This review summarizes current understanding around EV preservation, challenges in maintaining EV quality, and also bioengineering advances aimed at enhancing the long-term stability of EVs.

The effect of mechanical dry coating with magnesium stearate on flowability and compactibility of plastically deforming microcrystalline cellulose powders.

Mechanofusion is a dry coating method that can be used to improve the flowability of cohesive powder by coating host particles with a lubricant, for example magnesium stearate (MgSt). It has been shown previously that fragmenting material can under some circumstances be mechanofused with MgSt without impairing compactibility of the powder and without reducing the dissolution rate of the resulting tablets. However, the effects on material with viscoelastic behaviour, known to be sensitive for the negative effects of MgSt, is not known. Therefore, mechanofusion of microcrystalline cellulose (MCC) with MgSt was investigated in this study. Four MCC grades were mechanofused with different MgSt concentrations and process parameters, and the resulting flowability and compactibility were studied. Starting materials and low-shear blended binary mixtures were studied as a reference. Mechanofusion improved the flow properties of small particle size MCC powders (d50 < 78 µm) substantially, but increasing the MgSt content consequently resulted in weaker tablets. Larger particle size MCC grades, however, fractured under the shear forces during the mechanofusion process and hence their flow properties were decreased. Improvement of the flow properties but also the negative effects on compactibility of small particle size grades were observed even at relatively mild mechanofusion parameters and low lubricant concentrations.

Anatomy of psoas muscle innervation: Cadaveric study.

Hip flexion weakness is relatively common after lateral transpsoas surgery. Persistent weakness may result from injury to the innervation of the psoas major muscles (PMMs); however, anatomical texts have conflicting descriptions of this innervation, and the branching pattern of the nerves within the psoas major, particularly relative to vertebral anatomy, has not been described. The authors dissected human cadavers to describe the branching pattern of nerves supplying the PMMs. Sixteen embalmed cadavers were dissected, and the fine branching pattern of the innervation to the PMM was studied in 24 specimens. The number of branches and width and length of each branch of nerves to the PMMs were quantified. Nerve branches innervating the PMMs arose from spinal nerve levels L1-L4, with an average of 6.3 ± 1.1 branches per muscle. The L1 nerve branch was the least consistently present, whereas L2 and L3 branches were the most robust, the most numerous, and always present. The nerve branches to the psoas major commonly crossed the intervertebral (IV) disc obliquely prior to ramification within the muscle; 76%, 80%, and 40% of specimens had a branch to the PMM cross the midportion of the L2-3, L3-4, and L4-5 IV discs, respectively. The PMMs are segmentally innervated from the L2-L4 ventral rami branches, where these branches course obliquely across the L2-3, L3-4, and L4-5 IV discs. Knowledge of the mapping of nerve branches to the PMMs may reduce injury and the incidence of persistent weak hip flexion during lateral transpsoas surgery. Clin. Anat. 30:479-486, 2017. © 2017 Wiley Periodicals, Inc.

Single-step Coprocessing of Cohesive Powder via Mechanical Dry Coating for Direct Tablet Compression.

This study aims at testing the feasibility of a single-step coating process to produce a powder formulation of active and inactive ingredients for direct compression. A cohesive ibuprofen powder was coprocessed with a coating material, a binder (polyvinylpyrrolidone K25), and a superdisintegrant (crospovidone). Magnesium stearate (MgSt), l-leucine, and silica were selected as coating materials (1% w/w). A coprocessed powder without any coating material was employed as a control. Coating with MgSt, l-leucine, or silica produced significantly improved powder flow in comparison to the control batch. Robust tablets were produced from the processed powders for each coating material. The tablets compacted using the coated powders with MgSt or l-leucine also exhibited significantly lower tablet ejection forces than the control batch, demonstrating their lubrication effect. Furthermore, the disintegration time and dissolution rates of these tablets made of the formulations coprocessed with lubricants were enhanced, even for those coated with the hydrophobic material such as MgSt that has been previously reported to inhibit dissolution. However, the tablets made with silica-coated powders would not disintegrate. This study indicated the feasibility of a single-step dry coating process to produce powders with both flow-aid and lubrication effects, which are suitable for direct compression.

Measuring the impact of the flipped anatomy classroom: The importance of categorizing an assessment by Bloom's taxonomy.

The flipped classroom (FC) model has emerged as an innovative solution to improve student-centered learning. However, studies measuring student performance of material in the FC relative to the lecture classroom (LC) have shown mixed results. An aim of this study was to determine if the disparity in results of prior research is due to level of cognition (low or high) needed to perform well on the outcome, or course assessment. This study tested the hypothesis that (1) students in a FC would perform better than students in a LC on an assessment requiring higher cognition and (2) there would be no difference in performance for an assessment requiring lower cognition. To test this hypothesis the performance of 28 multiple choice anatomy items that were part of a final examination were compared between two classes of first year medical students at the University of Utah School of Medicine. Items were categorized as requiring knowledge (low cognition), application, or analysis (high cognition). Thirty hours of anatomy content was delivered in LC format to 101 students in 2013 and in FC format to 104 students in 2014. Mann Whitney tests indicated FC students performed better than LC students on analysis items, U = 4243.00, P = 0.030, r = 0.19, but there were no differences in performance between FC and LC students for knowledge, U = 5002.00, P = 0.720 or application, U = 4990.00, P = 0.700, items. The FC may benefit retention when students are expected to analyze material. Anat Sci Educ 10: 170-175. © 2016 American Association of Anatomists.

Applying surface energy derived cohesive-adhesive balance model in predicting the mixing, flow and compaction behaviour of interactive mixtures.

OBJECTIVE: In this study, we investigated the applicability of cohesive-adhesive balance (CAB) model to predict the interactive mixing behaviour of small excipient particles. Further, we also investigated the application of this CAB model to predict the flow and compactibility of resultant blends. METHODS: Excipients created by co-spraying polyvinylpyrrolidone (PVP, a model pharmaceutical binder) with various l-leucine concentrations were used for this study. Paracetamol was used as model active pharmaceutical ingredient (API). The surface energy was used to derive the work of cohesion (wco) and work of adhesion (wad) to predict the interactive mixing behaviour of the excipients with paracetamol. The blends were visualised under a scanning electron microscopy microscope to assess the interactive mixing behaviour. In addition, the flow performance and tabletting behaviour of various blends were characterised. RESULTS: The surface-energy derived work of adhesion (wad) between excipient and paracetamol particles increased, while the corresponding work of cohesion (wco) between excipient particles decreased, with increasing l-leucine concentrations. In blends for which the work of cohesion was higher than the work of adhesion (wco>wad), small excipient particles were apparent as agglomerates. For excipients with 5% and higher l-leucine concentrations, the work of adhesion between excipient and paracetamol particles was higher than or equivalent to the work of cohesion between excipient particles (wad⩾wco) and agglomerates were less apparent. This is an indicator of formation of homogeneous interactive mixtures. At 5% (w/w) excipient proportions, blends for which wad⩾wco demonstrated higher compactibility than other blends. Furthermore, at 10% (w/w) and higher excipient proportions, these blends also demonstrated better flow performance than other blends. CONCLUSION: In conclusion, this is the first study to demonstrate that surface-energy derived CAB data effectively predict the interactive mixing behaviour of small excipient particles. Furthermore, at certain proportions of small excipient particles the CAB model also predicts the flow and compaction behaviour of the API/excipient blends.

Effect of the deformability of guest particles on the tensile strength of tablets from interactive mixtures.

In this study, we investigated the influence of deformability of specifically-engineered guest particles on the tensile strength of tablets of interactive mixtures. The binder polyvinylpyrrolidone (PVP) of different molecular weights were spray dried with l-leucine to create guest particle formulations. The guest particle formulations were characterized by their particle size, surface l-leucine concentration and glass transition temperature (Tg). These spray-dried particles were then blended with paracetamol to form interactive mixtures, which were compacted into tablets and tablet tensile strength and elastic recovery were determined. The guest particles had particle diameters in the range of 1-10µm, and surfaces that were l-leucine enriched. The Tg of guest particle formulations increased with increasing molecular weight of the PVP. All the guest particle formulations formed an observed homogeneous interactive mixture with paracetamol. The tensile strength of the tablets of interactive mixtures increased with decreasing Tg of the guest particles. In these interactive mixtures, higher tensile strength was also associated with lower tablet elastic recovery. The elastic recovery of the tablets showed a correlation with the elastic recovery of the tablets of guest particles. Thus, our results indicated that the deformability of guest particles dictates the tensile strength of the tablets of these interactive mixtures.

The Two-Stage Examination: A Method to Assess Individual Competence and Collaborative Problem Solving in Medical Students.

PROBLEM: Effectively solving problems as a team under stressful conditions is central to medical practice; however, because summative examinations in medical education must test individual competence, they are typically solitary assessments. APPROACH: Using two-stage examinations, in which students first answer questions individually (Stage 1) and then discuss them in teams prior to resubmitting their answers (Stage 2), is one method for rectifying this discordance. On the basis of principles of social constructivism, the authors hypothesized that two-stage examinations would lead to better retention of, specifically, items answered incorrectly at Stage 1.In fall 2014, they divided 104 first-year medical students into two groups of 52 students. Groups alternated each week between taking one- and two-stage examinations such that each student completed 6 one-stage and 6 two-stage examinations. The authors reassessed 61 concepts on a final examination and, using the Wilcoxon signed ranked tests, compared performance for all concepts and for just those students initially missed, between Stages 1 and 2. OUTCOMES: Final examination performance on all previously assessed concepts was not significantly different between the one-and two-stage conditions (P = .77); however, performance on only concepts that students initially answered incorrectly on a prior examination improved by 12% for the two-stage condition relative to the one-stage condition (P = .02, r = 0.17). NEXT STEPS: Team assessment may be most useful for assessing concepts students find difficult, as opposed to all content. More research is needed to determine whether these results apply to all medical school topics and student cohorts.

Relationship between the cohesion of guest particles on the flow behaviour of interactive mixtures.

In this study, we aimed to investigate the effects cohesion of small surface-engineered guest binder particles on the flow behaviour of interactive mixtures. Polyvinylpyrrolidone (PVP) - a model pharmaceutical binder - was spray-dried with varying l-leucine feed concentrations to create small surface-engineered binder particles with varying cohesion. These spray-dried formulations were characterised by their particle size distribution, morphology and cohesion. Interactive mixtures were produced by blending these spray-dried formulations with paracetamol. The resultant blends were visualised under scanning electron microscope to confirm formation of interactive mixtures. Surface coverage of paracetamol by guest particles as well as the flow behaviour of these mixtures were examined. The flow performance of interactive mixtures was evaluated using measurements of conditioned bulk density, basic flowability energy, aeration energy and compressibility. With higher feed l-leucine concentrations, the surface roughness of small binder particles increased, while their cohesion decreased. Visual inspection of the SEM images of the blends indicated that the guest particles adhered to the surface of paracetamol resulting in effective formation of interactive mixtures. These images also showed that the low-cohesion guest particles were better de-agglomerated that consequently formed a more homogeneous interactive mixture with paracetamol compared with high-cohesion formulations. The flow performance of interactive mixtures changed as a function of the cohesion of the guest particles. Interactive mixtures with low-cohesion guest binder particles showed notably improved bulk flow performance compared with those containing high-cohesion guest binder particles. Thus, our study suggests that the cohesion of guest particles dictates the flow performance of interactive mixtures.

Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization.

This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of l-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without l-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance.

Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.