Lactose Carrier Research Articles

Quantifying the loading capacity of a carrier-based DPI formulation and its dependence on the blending process

Non-segregating ordered powder mixtures constituted by a coarse carrier fraction and finer components are at the basis of dry powders for inhalation pharmaceuticas. The estimation of the loading capacity, i.e. how many fines can be hosted on each carrier particle, is crucial to grant the product quality through a reproducible and affordable manufacturing process. We propose an approach based on the combination of sieve analysis, optical microscopy and powder bed permeability to quantify the loading capacity and understand the fines behavior, the impact of the mixing process was also investigated. We tested the method on model binary mixtures composed only of a coarse lactose carrier and micronized lactose fines as a surrogate of a real active pharmaceutical ingredient. The results provided by the different methods are consistent, the approach proved to be accurate and reproducible. The effect of different mixing parameters and equipment on the loading capacity is also discussed.

Excipient Interactions in Glucagon Dry Powder Inhaler Formulation for Pulmonary Delivery.

Purpose: This study describes the development and characterization of glucagon dry powder inhaler (DPI) formulation for pulmonary delivery. Lactose monohydrate, as a carrier, and L-leucine and magnesium stearate (MgSt) were used as dispersibility enhancers for this formulation. Methods: Using Fourier-transform infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), and Raman confocal microscopy, the interactions between glucagon and all excipients were characterized. The fine particle fractions (FPFs) of glucagon in different formulations were determined by a twin stage impinger (TSI) using a 2.5% glucagon mixture, and the glucagon concentration was measured by a validated LC-MS/MS method. Results: The FPF of the glucagon was 6.4%, which increased six-fold from the formulations with excipients. The highest FPF (36%) was observed for the formulation containing MgSt and large carrier lactose. The FTIR, Raman, and DSC data showed remarkable physical interactions of glucagon with leucine and a minor interaction with lactose; however, there were no interactions with MgSt alone or mixed with lactose. Conclusion: Due to the interaction between L-leucine and glucagon, leucine was not a suitable excipient for glucagon formulation. In contrast, the use of lactose and MgSt could be considered to prepare an efficient DPI formulation for the pulmonary delivery of glucagon.

In vitro and in vivo evaluation of porous lactose/mannitol carriers for solubility enhancement of poorly water-soluble drugs

The application of porous materials as drug carriers represents a new solubility enhancement strategy for poorly soluble drugs. In this study, porous lactose or mannitol carriers were prepared by a combined spray drying and template removal method with Indomethacin loaded as a model drug. In vitro dissolution test and in vivo absorption study were employed to evaluate the capacity of the porous carriers on solubility enhancement of Indomethacin. Porous lactose carriers displayed higher surface area and larger pore volume than that of mannitol, which was consistent with the corresponding amount of drug loading. Compared with the physical mixtures, indomethacin loaded into the porous carriers displayed significantly higher dissolution rate, with more than 80% of the loaded drug released in 10 min. Results of animal experiments in beagle dogs showed that the prepared Indomethacin-loaded porous lactose can enhance the in vivo absorption of Indomethacin. The analysis in gender difference suggested that Indomethacin was absorbed faster in female beagle dogs than that in male. The fabrication of porous framework from food-grade materials and the proved effectiveness on solubility enhancement further expand the capability of spray drying engineering of pharmaceutical particles.

Linking carrier morphology to the powder mechanics of adhesive mixtures for dry powder inhalers via a blend-state model

The aim of this study was to investigate how the carrier morphology affects the expression of blend states in adhesive mixtures as a function of surface coverage ratio (SCR) and to identify where transitions between the different states occur. Adhesive mixtures of five lactose carriers with varying contents of lactose fines, corresponding to blends with different SCR ranging from 0 to 6, were produced by low-shear mixing. The powder mechanics of the mixtures were characterized by bulk density, compressibility and permeability. The appearance of the carriers and blends was studied by scanning electron microscopy, light microscopy and atomic force microscopy. The size and morphology of the carriers had a crucial impact on the evolution of the blend state, and affected the powder mechanical properties of the mixtures. It was found that smaller carriers with little or no surface irregularities were more sensitive to additions of fines resulting in self-agglomeration of fines at relatively low SCR values. On the contrary, carriers with irregular surface structures and larger sizes were able to reach higher SCR values before self-agglomeration of fines occurred. This could be attributed to an increased deagglomeration efficiency of irregular and larger carriers and to fines predominantly adhering to open pores.

Hydroxypropyl-β-cyclodextrin as anti-hygroscopicity agent inamorphous lactose carriers for dry powder inhalers

Carrier based dry powder inhalers (DPIs) have become a hotspot in recent years. Lactose is the most commonly used carrier in DPI, while its further application was hindered by its hygroscopicity. Agglomeration induced by hygroscopicity would cause the deterioration of aerosolization performance. In this study, cyclodextrin-lactose binary carriers (CLBCs) were produced by spray-drying so as to surmount the hygroscopicity. Physicochemical attributes of CLBCs were explored in detail. Hygroscopicity of CLBCs was elucidated by dynamic vapor sorption study. Aerosolization performance of its corresponding DPIs was evaluated by the next generation impactor (NGI). In addition, the preliminary reserach on the formation mechanism of CLBCs was carried out. The optimal formulation of CLBC (L3) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. To be concise, the moisture uptake of L3 was ca. 2.8% which was far lower than spray-driedlactose (L0, ca. 50.1%). L3 exhibited a high fine particle fraction value of 59.16 ± 1.41 and it was 3.7-fold against L0. After 10-day storage in high humidity, L3 maintained its physicochemical properties and the superior aerosolization performance. It was proved that CLBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI.

Preparation and Characterization of Spray-Dried Inhalable Powders Containing Polymeric Micelles for Pulmonary Delivery of Paclitaxel in Lung Cancer

Local delivery of chemotherapeutic drugs to the lungs offers many advantages for lung cancer treatment compared to conventional systemic chemotherapy. In the present study, novel mixed polymeric micelles based on tocopheryl succinate-polyethylene glycol 1000 and 5000 Da (TPGS1K and TPGS5K) were synthesized and loaded with paclitaxel (PTX). Then, the optimized micelles were incorporated as colloidal drug delivery system into lactose carrier particles using a spray drying technique. The mixed micelles of TPGS5K and TPGS1K in different molar ratios (10:0, 7:3, 5:5, 3:7, 0:10) were prepared and physicochemical properties including: particle size, zeta potential, critical micelle concentration (CMC), drug loading, drug release rate, and in vitro cytotoxicitywere investigated in details. The optimized nanoparticles were co-spray dried with lactose carriers to produce the spherical particle morphology of the inhalable particles. Particle sizes and zeta potentials of the different formulations varied in the range of 102 to 196 nm and -9.4 to -13.8 mV, respectively. The lowest CMC values were calculated for 5:5 and 7:3 combinations (16.33 and 17.89 µM, respectively). The drug release rate from different formulations were very slow and only 30% of the drug was released during 72 h. Cytotoxicity assay demonstrated increased cytotoxic activity of PTX-loaded mixed micelles compared to the free drug. The in vitro deposition data indicated that spray drying of PTX-loaded micelles with lactose resulted in the production of inhalable powders with the high fine particle fraction (60%). These results demonstrate that this novel PTX-loaded micelles embedded in dry powder inhalation aerosol platform has a great potential to be used in lung cancer treatment.

Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler

The fine particle fraction is a key indicator of therapeutic effectiveness of inhaled pharmaceutical aerosols. This paper presents a fluorescence imaging technique to visualise and characterise the emission of active pharmaceutical ingredient (API) fines in model formulations containing coarse lactose carrier and 1.5–2 μm diameter fluorescent microspheres (model API fines). A two-camera arrangement was used to acquire simultaneous images of spatial and temporal distribution of model API fines and fluidised powder formulation near the mouthpiece exit of a DPI. Digital image analysis showed that the model API fines were released along with the bulk of the powder dose. More rapidly accelerating airflows were found to cause earlier release of API fines. The fluorescence imaging technique analyses a substantial fraction of the aerosol plume and was found to provide effective time-resolved characterisation of the de-aggregation and release of API fines with consistent results across a wide range of model API concentrations. Future studies should demonstrate the usefulness of the fluorescence imaging technique across different formulations and DPI devices.

Assessment of Dry Powder Inhaler Carrier Targeted Design: A Comparative Case Study of Diverse Anomeric Compositions and Physical Properties of Lactose.

The pulmonary administration landscape has rapidly advanced in recent years. Targeted design of particles by spray-drying for dry powder inhaler development offers an invaluable tool for engineering of new carriers. In this work, different formulation and process aspects of spray-drying were exploited to produce new lactose carriers. Using an integrated approach, lactose was spray-dried in the presence of polyethylene glycol 200 (PEG 200), and the in vitro performance of the resulting particles was compared with other grades of lactose with varying anomeric compositions and/or physical properties. The anomeric composition of lactose in lactose-PEG 200 feed solutions of variable compositions was analyzed via polarimetry at different temperatures. These results were correlated with the solid-state and anomeric composition of the resulting spray-dried particles using modulated differential scanning calorimetry and wide-angle X-ray scattering. The distinct selected grades of lactose were characterized in terms of their micromeritic properties using laser diffraction, helium pycnometry, and gas adsorption, and their particle surface morphologies were evaluated via scanning electron microscopy. Adhesive mixtures of the different lactose carriers with inhalable-sized salbutamol sulfate, as a model drug, were prepared in low doses and evaluated for their blend homogeneity and aerodynamic performance using a Next Generation Impactor. Characterization of the spray-dried particles revealed that predominantly crystalline (in an anomeric ratio 0.8:1 of α to β) spherical particles with a mean size of 50.9 ± 0.4 μm could be produced. Finally, it was apparent that micromeritic, in particular, the shape, and surface properties (inherent to solid-state and anomeric composition) of carrier particles dominantly control DPI delivery. This provided an insight into the relatively inferior performance of the adhesive blends containing the spherical spray-dried lactose-PEG 200 composites.

Limitations of high dose carrier based formulations

PurposeThis study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. MethodsFive formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). ResultsIncreasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. ConclusionAs the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations.

The role of lactose carrier on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation

In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier. In all of the carrier-based formulations, the flow properties were improved compared with bosentan microparticles alone, in the following order spray-dried, sieved and milled lactose. The aerodynamic characteristics of each were evaluated by particle image velocimetry and Andersen cascade impactor™. Depending on the lactose carrier type, particle dispersion showed different flow characteristics. In the spray-dried lactose, the formulation was dispersed fast in the only frontal direction, while the milled and sieved lactose formulations formed a relatively slower S-shaped and fountain-shaped flow stream, respectively. In addition, milled and sieved lactose formulations showed that the drug particles were readily liberated from the lactose carrier, and demonstrated significantly higher aerosol performance than spray-dried lactose.

Characterizing the Surface Roughness Length Scales of Lactose Carrier Particles in Dry Powder Inhalers.

Surface roughness is well recognized as a critical physical property of particulate systems, particularly in relation to adhesion, friction, and flow. An example is the surface property of carrier particles in carrier-based dry powder inhaler (DPI) formulations. The numerical characterization of roughness remains rather unsatisfactory due to the lack of spatial (or length scale) information about surface features when a common amplitude parameter such as average roughness ( Ra) is used. An analysis of the roughness of lactose carrier particles at three different length scales, designed for specificity to the study of interactive mixtures in DPI, was explored in this study. Three Ra parameters were used to represent the microscale, intermediate scale, and macroscale roughness of six types of surface-modified carriers. Coating of micronized lactose fines on coarse carrier particles increased their microroughness from 389 to 639 nm while the macroroughness was not affected. Roller compaction at higher roll forces led to very effective surface roughening, particularly at longer length scales. Changes in Ra parameters corroborated the visual observations of particles under the scanning electron microscope. Roughness at the intermediate scale showed the best correlation with the fine particle fraction (FPF) of DPI formulations. From the range of 250 to 650 nm, every 100 nm increase in the intermediate roughness led to ∼8% increase in the FPF. However, the effect of surface roughness was greatly diminished when fine lactose (median size, 9 μm) of comparable amounts to the micronized drug were added to the formulation. The combination of roughness parameters at various length scales provided much discriminatory surface information, which then revealed the "quality" of roughness necessary for improving DPI performance.

Investigations on the Mechanism of Magnesium Stearate to Modify Aerosol Performance in Dry Powder Inhaled Formulations

The potential of the force control agent magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. The excipient-blends were investigated with analytical techniques including time-of-flight secondary ion mass spectrometry and single particle aerosol mass spectrometry (SPAMS), and particle size, morphology, and surface properties were evaluated. Excipient-blends were manufactured either by high-shear or low-shear blending lactose carrier with different amounts of MgSt in the range from 0% to 10% (w/w). Fluticasone propionate (FP) and salmeterol xinafoate (SX) used as model active pharmaceutical ingredients were added by low-shear mixing. The in vitro aerosol performance in terms of aerodynamic particle size distribution and fine particle fraction (FPF) of the FP and SX DPI formulations was evaluated with the Next Generation Impactor and also with SPAMS using a Breezhaler® inhalation device. The distribution of MgSt on the lactose carrier in the blends was visualized and found to depend strongly on the blending method. This affected drug particle detachment from the carrier and thus impacted aerosol performance for FP and SX. Compared with blends without force control agent, low-shear blending of MgSt increases the FPF of the model drug SX, whereas high-shear blending significantly increased FPF of both SX and FP. The interactions between drug and carrier particles were substantially affected by the choice of blending technique of MgSt with lactose. This allows detailed control of aerosol performance of a DPI by an adequate choice of the blending technique. SPAMS successfully demonstrated that it is capable to distinguish changes in DPI formulations blended with different amounts of MgSt, and additional information in terms of dispersibility of fine particles could be generated.

Powder flow analysis: A simple method to indicate the ideal amount of lactose fines in dry powder inhaler formulations

Many efforts have been made in the past to understand the function of lactose fines which are given as a ternary component to carrier-based dry powder inhaler formulations. It is undisputed that fines can significantly improve the performance of such formulations, but choosing the right amount of fines is a crucial point, because too high concentrations can have negative effects on the dispersion performance. The aim of this study was to indicate the optimal concentration of fines with a simple test method. For this purpose, mixtures with salbutamol sulfate and two different lactose carriers were prepared with a high shear mixer, measured with a FT4 powder rheometer and tested for fine particle delivery with two different inhaler devices. A correlation between the fluidization energy, measured with the aeration test set up, and the fine particle fractions (FPF) could be proven. This also applied for the aeration ratio, as well as the permeability of the powder samples. In addition, drug-free mixtures hardly differed in their rheological properties from mixtures containing the active pharmaceutical ingredient (API), which indicates that the method could be suitable for cost-saving screening trials. Furthermore, important aspects that explain the function of fines, such as the saturation of active sites, the formation of agglomerates and an increase in fluidization energy, could be shown in this study.

Understanding phospholipid function: Why are there so many lipids?

In the 1970s, phospholipids were still considered mere building blocks of the membrane lipid bilayer, but the subsequent realization that phospholipids could also serve as second messengers brought new interest to the field. My own passion for the unique amphipathic properties of lipids led me to seek other, non-signaling functions for phospholipids, particularly in their interactions with membrane proteins. This seemed to be the last frontier in protein chemistry and enzymology to be conquered. I was fortunate to find my way to Eugene Kennedy's laboratory, where both membrane proteins and phospholipids were the foci of study, thus providing a jumping-off point for advancing our fundamental understanding of lipid synthesis, membrane protein biosynthesis, phospholipid and membrane protein trafficking, and the cellular roles of phospholipids. After purifying and characterizing enzymes of phospholipid biosynthesis in Escherichia coli and cloning of several of the genes encoding these enzymes in E. coli and Saccharomyces cerevisiae, I was in a position to alter phospholipid composition in a systematic manner during the cell cycle in these microorganisms. My group was able to establish, contrary to common assumption (derived from the fact that membrane proteins retain activity in detergent extracts) that phospholipid environment is a strong determining factor in the function of membrane proteins. We showed that molecular genetic alterations in membrane lipid composition result in many phenotypes, and uncovered direct lipid-protein interactions that govern dynamic structural and functional properties of membrane proteins. Here I present my personal "reflections" on how our understanding of phospholipid functions has evolved.

PEGylated composite nanoparticles of PLGA and polyethylenimine for safe and efficient delivery of pDNA to lungs

Achieving stable, efficient and non-toxic pulmonary gene delivery is most challenging requirement for successful gene therapy to lung. Composite nanoparticles (NPs) of the poly(lactic-co-glycolic acid) (PLGA) and cationic polymer polyethyleneimine (PEI) is an efficient alternative to viral and liposomal vectors for the pulmonary delivery of pDNA. NPs with different weight ratios (0–12.5%w/w) of PLGA/PEI were prepared and characterized for size, morphology, surface charge, pDNA loading and in vitro release. The in vitro cell uptake and transfection studies in the CFBE41o–cell line revealed that NPs with 10% w/w PEI were more efficient but they exhibited significant cytotoxicity in MTT assays, challenging the safety of this formulation. Surface modifications of these composite NPs through PEGylation reduced toxicity and enhanced cellular uptake and pDNA expression. PEGylation improved diffusion of NPs through the mucus barrier and prevented uptake by pulmonary macrophages. Finally, PEGylated composite NPs were converted to DPI by lyophilization and combined with lactose carrier particles, which resulted in improved aerosolization properties and lung deposition, without affecting pDNA bioactivity. This study demonstrates that a multidisciplinary approach may enable the local delivery of pDNA to lung tissue for effective treatment of deadly lung diseases.

Influence of Added of Fines to the Decanted Carrier Surfaces Used in Dry Powder Formulations

Investigation of the effect of adding carrier fines to the wet decanted carriers and the subsequent effects on the in vitro deposition of salbutamol sulphate. Methods: The wet decantation process used to remove the surface carrier fines carried out nine time for lactose and mannitol carriers. Addition lactose fines up to 8% to decanted lactose. Additionally, mannitol fines up to 16% were added to decanted mannitol. In vitro deposition carried out for those treated carriers after mixing with salbutamol sulphate using the NGI. Results: There were significant increase in fine particle fraction (FPFs). This probably by reducing drug-carrier adhesion and allowing easy detachment of the drugs from the carrier surface. Although this addition of fines could not revert the FPFS to the original value of the untreated carriers. Conclusions: Addition of micronized carriers to decanted carriers found to increase significantly the dispersion of the drug and the in vitro deposition.

Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading

Previously, granulated lactose carriers were shown to improve uniformity and aerosolization of a low-dose model drug. In the present study, the blending uniformity and aerosol dispersion performance were assessed for 2 model drugs salbutamol sulfate (SS) and rifampicin (RIF), blended at high loadings (10% or 30% drug) with granulated lactose carriers. The model drug powders differed in particle size distribution, morphology, density, and surface energies. Content uniformity of RIF blends was better than that of SS. Aerosolization studies showed that all blend formulations had acceptable emitted fractions (>70%). The SS blends showed low induction-port deposition (6%-10%) compared to RIF (5%-30%). This difference was greater at high flow rates. At 90 L/min, the low induction port deposition of SS blends allowed high fine particle fraction (FPF) of 73%-81%, whereas the FPF of the RIF blends was around 43%-45% with higher induction port deposition. However, SS blends exhibited strong flow rate–dependent performance. Increasing the flow rate from 30 L/min to 90 L/min increased SS FPF from approximately 20% to 80%. Conversely, RIF blends were flow rate and drug loading independent. It was concluded that the aerosolization of high drug–loaded dry powder inhaler formulations using granulated lactose, particularly flow rate dependency, varies with active pharmaceutical ingredient properties.

Exploring the protective effects of calcium-containing carrier against drying-induced cellular injuries of probiotics using single droplet drying technique

Protective carriers that encapsulate probiotics in spray drying could improve the survival ratio of dried cells through different mechanisms. Unveiling the protective mechanism of each carrier will contribute to a rational design of high performance carrier formulation. This study utilized single droplet drying (SDD) technique to investigate the effects of calcium cation in varied carrier formulation. Inactivation histories of Lactobacillus rhamnosus GG (LGG) in different carriers were compared, and cellular injury history of probiotics during droplet drying was studied for the first time. Adding 1mM CaCl2 to lactose carrier protected cell viability, mitigated cellular injuries, and enhanced regrowth capability as drying progressed, demonstrating the positive effect of Ca2+ with possible mechanism of stabilizing sub-cellular structures. At later drying stages, cell survival in Lac/Ca carrier was increased by 0.5–1.5 log on selective media compared to lactose carrier. Supplementing calcium-binding agents lowered the protective effect, shortening the initiation of rapid cell inactivation down to 120s of drying. Adding CaCl2 to trehalose carrier barely improved cell survival, indicating that the protective effect could be influenced by carrier formulation. Pure trehalose carrier exerted excellent protection on LGG, supporting cells to regrow in liquid rich medium even after 180s of drying. The protection of trehalose may stem from stabilization of sub-cellular structures, which possibly overlap the effect of Ca2+. The findings suggested that high performance carrier formulation might be developed by combining carrier materials with different protective mechanisms, for maximizing the survival of active dry probiotics in industrial spray drying operation.

Impact of feed counterion addition and cyclone type on aerodynamic behavior of alginic-atenolol microparticles produced by spray drying

The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) and systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration. In a previous work, atenolol was combined with alginic acid (AA) and microparticles were developed using spray-drying (SD) technology. Different AA/atenolol ratios, total feed solid content and operative variables were previously explored. In order to improve particle quality for inhalatory administration and the SD yield, in this work the AA acid groups not neutralized by atenolol were kept either free or neutralized to pH∼7 and two different SD cyclones were used. Particle morphology, flow properties, moisture uptake and in vitro aerosolization behavior at different pressure drops were studied. When the AA acid groups were neutralized, particle size decreased as a consequence of the lower feed viscosity. The SD yield and in vitro particle deposition significantly increased when a high performance cyclone was employed, and even when lactose carrier particles were not used. Although the in vitro particle deposition decreased when the storage relative humidity increased, the developed SD powders showed adequate characteristics to be administered by inhalatory route up to storage relative humidities of about 60%.

Preparation of slab-shaped lactose carrier particles for dry powder inhalers by air jet milling

Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e., classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm. The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.