| 1. |
- Lindman, Björn, et al.
(författare)
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Polymer-surfactant interactions-recent developments
- 2018
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Ingår i: Interactions of Surfactants with Polymers and Proteins. - : CRC Press. - 9781351082235 - 0849367840 - 9781315894683 ; , s. 203-276
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Bokkapitel (refereegranskat)
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| 2. |
- Linse, Sara, et al.
(författare)
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The unhappy chaperone
- 2021
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Ingår i: QRB Discovery. - : Cambridge University Press (CUP). - 2633-2892. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Chaperones protect other proteins against misfolding and aggregation, a key requirement for maintaining biological function. Experimental observations of changes in solubility of amyloid proteins in the presence of certain chaperones are discussed here in terms of thermodynamic driving forces. We outline how chaperones can enhance amyloid solubility through the formation of heteromolecular aggregates (co-Aggregates) based on the second law of thermodynamics and the flux towards equal chemical potential of each compound in all phases of the system. Higher effective solubility of an amyloid peptide in the presence of chaperone implies that the chemical potential of the peptide is higher in the aggregates formed under these conditions compared to peptide-only aggregates. This must be compensated by a larger reduction in chemical potential of the chaperone in the presence of peptide compared to chaperone alone. The driving force thus relies on the chaperone being very unhappy on its own (high chemical potential), thus gaining more free energy than the amyloid peptide loses upon forming the co-Aggregate. The formation of heteromolecular aggregates also involves the kinetic suppression of the formation of homomolecular aggregates. The unhappiness of the chaperone can explain the ability of chaperones to favour an increased population of monomeric client protein even in the absence of external energy input, and with broad client specificity. This perspective opens for a new direction of chaperone research and outlines a set of outstanding questions that aim to provide additional cues for therapeutic development in this area.
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| 3. |
- Mosén, Kristina, et al.
(författare)
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Particle formation and capture during spray drying of inhalable particles
- 2004
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Ingår i: Pharmaceutical Development and Technology. - 1083-7450. ; 9:4, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- An investigation of the spray drying process is made in great detail regarding particle formation and capture efficiency with focus on the production of inhalable particles. Mannitol was spray dried as model substance and the spray-dried products were characterized. The resulting products consisted of smooth spheres with a volume median diameter of 2.2-5.5 mum, and narrow size distributions. The investigation was performed in pilot scale of sufficient size to draw general conclusions and make some recommendations. It has been shown that the size of particles is decreased when the feed concentration is decreased, the nozzle gas/feed flow mass ratio increased, and the droplet size decreased. The collection efficiency of the cyclone device used in this study was shown to have a cut-off of 2 mum, i.e., 50% of the particles less than 2 mum are not captured. The data reported indicate that the majority of the single particles formed here, <5 μm, arise from single droplets (of about 10 μm) and are solid, nonporous particles.
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| 4. |
- Mosén, Kristina, et al.
(författare)
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The apparent plasticizing effect of polyethylene glycol (PEG) on the crystallinity of spray dried lactose/PEG composites
- 2006
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411. ; 64:2, s. 206-211
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Tidskriftsartikel (refereegranskat)abstract
- Aqueous solutions of lactose and polyethylene glycol (PEG) were spray dried in a Buchi Model 191 spray dryer with the aim to investigate the effect of PEG on the crystallinity of the composite. A PEG concentration of 10.7% by weight of solids was studied for PEG 200, 600, 1500, 4000 and 8000. For PEG 200 and 4000 additional concentrations from 1.5-19.3% to 1.5-32.4%, respectively, were investigated. The spray dried composites were analysed with X-ray powder diffraction and modulating differential scanning calorimetry. The crystallinity of lactose in the composites varied from 0% to 60%, dependent on the molecular weight and concentration of PEG. Apparently, lactose crystallinity is promoted by low molecular weight and high concentration of the PEG. PEG did not affect the lactose glass transition temperature. It is suggested that lactose and PEG are solidified separately during spray drying and that partial crystallization of lactose is associated with effects of PEG on the rate of drying.
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| 5. |
- Rudén, Jonas, et al.
(författare)
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Effect of pressure drop on blend state-dispersibility relationships of adhesive mixtures for inhalation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The blend state model, describing the spatial distribution of fine particles within an adhesive mixture, was investigated by varying the pressure drop (airflow) used to disperse and aerosolize budesonide containing mixtures. The dispersibility was assessed using a ScreenHaler device with a Turbuhaler mouthpiece and a next generation impactor. The pressure drop was set to 0.5, 2 or 4 kPa during the experiments. It can be concluded that in the S1 state, where the fines are situated in the cavities, the formulation disperses linearly with increased pressure drop. However, when an adhesion layer has formed on the carrier surface (i.e., the S2 state and above) a critical pressure drop must be reached to properly aerosolize the powder. Above the S2 transition, the structure of the adhesion layer, is thus more important than the pressure drop. A mixture containing inert lactose fines to saturate the S1 state, followed by addition of budesonide displayed an increase in the fine particle fraction as compared to the S1 only budesonide mixture. This provides support that the blend state model can be used as a tool to improve the optimization of adhesive mixtures for dry powder inhalers.
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| 6. |
- Rudén, Jonas, et al.
(författare)
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Effect of pressure drop on the in vitro dispersion of adhesive mixtures of different blend states for inhalation
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the effect of pressure drop (Delta P) on the in vitro dispersion of a series of carrier-based adhesive mixtures of different fines-to-carrier proportions, corresponding to the four different blend states of the blend state model, i.e. S1 to S3, was investigated. Four binary and one ternary adhesive mixture consisting of lactose carrier and budesonide fines and lactose fines were prepared. The dispersion was assessed using a next generation impactor (NGI) at Delta P of 0.5, 2 and 4 kPa. For the S1 mixture, where the fines were located in surface cavities of the carrier, the fine particle fraction (FPF) increased nearly linearly with Delta P. For S2 and S3 mixtures, with adhesion layers on the enveloped carrier surface, the FPF-Delta P relationships were bended and approached a plateau. Examination of powder captured in the pre-separator of the NGI led to the conclusion that the dispersion of these adhesive mixtures occurred by erosion of the adhesion layer, i.e. budesonide was liberated as single particles or micro-agglomerates. It is concluded that the FPF-Delta P relationships were dependent on the blend state and for the S2 and S3 mixtures, a critical pressure drop was identified above which the pressure drop had a limited effect on the FPF.
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| 7. |
- Rudén, Jonas, et al.
(författare)
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Linking carrier morphology to the powder mechanics of adhesive mixtures for dry powder inhalers via a blend-state model
- 2019
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 561, s. 148-160
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Rudén, Jonas, et al.
(författare)
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On the relationship between blend state and dispersibility of adhesive mixtures containing active pharmaceutical ingredients
- 2021
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 2590-1567. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The objectives of this investigation were to study the evolution in blend state of adhesive mixtures containing the active pharmaceutical ingredients (APIs) salbutamol, budesonide and AZD5423 and to study the relationship between blend state and dispersibility of the mixtures, as assessed by the fine particle fraction (FPF). A series of adhesive mixtures of varied fines concentration were prepared for each API using the same type of carrier. Based on visual examination and powder mechanics, blend states were identified and summarized as blend state maps for each API. The dispersibility of the mixtures was studied using a Fast Screening Impactor (FSI) equipped with a ScreenHaler. The evolution in blend state differed between the APIs in terms of the width of the blend states. The structure of the adhesion layer also differed between the APIs, from relatively uniform to a heterogeneous layer with small agglomerates dispersed on the carrier surface. All three APIs expressed a similar type of bended relationship between FPF and fines concentration. However, the initial rate of increase and the fines concentration of the plateau differed between the APIs. The adhesive mixtures of all APIs followed the three main states in terms of structural evolution and the overall shape of the FPF-fines concentration profiles could be explained by the evolution in blend state. It is proposed that the structure of the adhesion layer is an important factor explaining the differences in blend state - blend dispersibility relationships between the APIs.
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| 9. |
- Rudén, Jonas
(författare)
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Powder mechanics and dispersion properties of adhesive mixtures for dry powder inhalers : Conceptualized as a blend state model
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inhaled medicines is a therapy that dates back several thousands of years. Nowadays, using various types of inhaler devices to deliver active pharmaceutical ingredients (APIs) to treat respiratory diseases has become common practice. One such device is the dry powder inhaler (DPI) which often contains an adhesive powder mixture consisting of micron-sized API particles and larger inert particles (carriers). The general goal of a DPI formulation is to reach as high inhalable dose (dispersibility) as possible while maintaining a low dose variability. In addition, the formulation has to be stable during manufacturing and handling to avoid segregation. In this thesis, critical properties of adhesive mixtures for DPIs have been identified and summarized in a blend state model that describes the spatial distribution of API- and carrier particles in a mixture. The model consists of four distinct states, which are identified using a combination of powder mechanical analysis and imaging techniques. In the first state, denoted S1, the drug deposits at the open pores of the carriers resulting in a denser powder packing but a low dispersibility. At the second state, S2a, the drug will adhere to the outer carrier surfaces, which results in a more porous powder packing and increased dispersibility. Following further increases in drug load, reaching the S2b state, the adhering drug layer grows in complexity resulting in further reductions in powder density but with additional increases in dispersibility. At the final state, S3, the mixture is oversaturated with fines, which results in segregation and large self-agglomerates that are poorly dispersed during an inhalation experiment. The evolution of the blend state was found to be dependent on the carrier and API properties such as size and shape. Irregular carriers could handle higher drug loads before segregation occurred, while irregular API particles formed more porous adhesion layers resulting in lower drug loads. In terms of dispersibility, it was found that porous adhesion layers were more easily dispersed than coherent adhesion layers. When varying the pressure drop (airflow rate), the dispersibility of the S1 state increased linearly with higher pressure drops. However, S2a-S3 were more or less insensitive to increased pressure drops above a certain critical pressure drop. With the blend state model and the mapping of the evolution in blend state with increased drugs loads, the formulation work can ideally be improved leading to more effective treatments for patients.
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| 10. |
- Rudén, Jonas, et al.
(författare)
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Relationships between surface coverage ratio and powder mechanics of binary adhesive mixtures for dry powder inhalers
- 2018
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Ingår i: International Journal of Pharmaceutics. - : ELSEVIER SCIENCE BV. - 0378-5173 .- 1873-3476. ; 541:1-2, s. 143-156
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper was to study relationships between the content of fine particles and the powder mechanics of binary adhesive mixtures and link these relationships to the blend state. Mixtures with increasing amounts of fine particles (increasing surface coverage ratios (SCR)) were prepared using Lactopress SD as carrier and micro particles of lactose as fines (2.7 mu m). Indicators of unsettled bulk density, compressibility and flowability were derived and the blend state was visually examined by imaging. The powder properties studied showed relationships to the SCR characterised by stages. At low SCR, the fine particles predominantly gathered in cavities of the carriers, giving increased bulk density and unchanged or improved flow. Thereafter, increased SCR gave a deposition of particles at the enveloped carrier surface with a gradually more irregular adhesion layer leading to a reduced bulk density and a step-wise reduced flowability. The mechanics of the mixtures at a certain stage were dependent on the structure and the dynamics of the adhesion layer and transitions between the stages were controlled by the evolution of the adhesion layer. It is advisable to use techniques based on different types of flow in order to comprehensively study the mechanics of adhesive mixtures.
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