| 1. |
- Bredenberg, Susanne, et al.
(författare)
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Evaluation of a sieve classification method for characterization of low-dose interactive mixtures
- 2013
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Ingår i: Pharmaceutical development and technology (Print). - : Informa Healthcare. - 1083-7450 .- 1097-9867. ; 18:6, s. 1366-1371
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated a sieve classification method for evaluating carrier materials and particle size fractions, which could be a valuable tool in the early development of pharmaceutical dosage forms containing low-dose interactive mixtures. When developing new products based on interactive mixtures, it is essential to ensure that the drug particles are successfully deagglomerated and have adhered to the carrier particles. In this study, the effect on the demixing potential (DP) of low-dose interactive mixtures was assessed for various carrier particle sizes and surface textures. The model drug used was sodium salicylate and the tested carriers were lactose, mannitol, and isomalt. The results showed that the lowest DPs, i.e. the most mechanically stable mixtures, were obtained with lactose. Furthermore, for interactive mixtures, small carrier particles and/or a narrow carrier particle size range are essential for obtaining a low DP and high homogeneity. Calculation of the DP provided a reliable estimate of the quality of the low-dose interactive mixtures used in this study.
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| 2. |
- El-Serafi, Ibrahim, et al.
(författare)
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Pre-formulation investigations for establishing a protocol for treosulfan handling and activation
- 2019
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Ingår i: Pharmaceutical development and technology (Print). - : TAYLOR & FRANCIS LTD. - 1083-7450 .- 1097-9867. ; 24:5, s. 639-648
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Treosulfan is an alkylating agent that is used for the treatment of ovarian cancer and for conditioning prior to stem cell transplantation. It is a prodrug that is activated non-enzymatically to two active epoxides. Objectives: To optimize a protocol for both in vivo samples handling and in vitro drug preparation. Treosulfan stability was tested in biological fluids at different conditions as well as for its cytotoxicity on cell lines. Results: Plasma samples can be safely frozen for a short period up to 8 h, however; for longer periods, samples should be acidified. Urine samples and cell culture media can be safely frozen regardless their pH. For in vitro investigations, incubation of treosulfan at 37 degrees C for 24 h activated 100% of the drug. Whole blood acidification should be avoided for the risk of hemolysis. Finally; treosulfan cytotoxicity on HL-60 cells has increased following pre-incubation for 24 h at 37 degrees C compared to K562 cell line. Conclusion: The stability profiling of treosulfan provided a valuable reference for handling of biological samples for both in vivo and in vitro studies. These results can be utilized for further investigations concerning the drug kinetics and dynamics in addition to the development of new pharmaceutical formulations.
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| 3. |
- Fredenberg, Susanne, et al.
(författare)
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Effect of divalent cations on pore formation and degradation of poly(D,L-lactide-co-glycolide).
- 2007
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Ingår i: Pharmaceutical Development and Technology. - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 12:6, s. 563-572
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Tidskriftsartikel (refereegranskat)abstract
- Poly(D,L-lactide-co-glycolide) (PLG) is probably the biodegradable polymer most often used for polymeric controlled-release formulations. Different salts have been shown to affect the swelling and degradation of PLG, which, in turn, affect the release of encapsulated drugs. In this investigation the effect of divalent cations was especially investigated. Films of PLG were incubated in phosphate buffer saline (PBS), a buffer containing salts similar to plasma, Hepes buffer, and Hepes buffer with ZnCl2, CaCl2, MgCl2, or Na2CO3 added. Pore formation at the surface and inside the film was analyzed by scanning electron microscopy. The samples were also analyzed gravimetrically at predetermined intervals to determine the mass loss, and for some samples the pH within the PLG films was determined by confocal microscopy. Pores were formed faster in the presence of all divalent cations, and the results indicated a greater degradation rate in the presence of Zn2+. The catalyzing effect of the divalent cations on degradation was attributed to their ability to act as Lewis acids. Pores were formed more slowly in PBS than in a buffer containing salts similar to plasma, which should be considered when choosing the in vitro release medium.
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| 4. |
- Fredenberg, Susanne, et al.
(författare)
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Measurement of protein diffusion through poly(D,L-lactide-co-glycolide)
- 2005
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Ingår i: Pharmaceutical Development and Technology. - 1083-7450. ; 10:2, s. 299-307
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Tidskriftsartikel (refereegranskat)abstract
- A novel method was developed for studying the diffusion of proteins through poly(D,L-lactide-co-glycolide) (PLG), using a diffusion cell. To develop improved formulations for the controlled release of encapsulated drugs it is important to understand the underlying release mechanisms. When using low-molecular-weight PLG as the release-controlling polymer, diffusion through the pores is often proposed as the main release mechanism. The experimental set-up and method of determining the diffusion coefficient were thoroughly evaluated with regard to the reliability and the influence of the stirring rate. A procedure for spraying thin films of PLG onto a filter, which could be placed in the diffusion cell, was optimized. The method was then applied to the determination of the diffusion coefficient of human growth hormone (hGH) through a PLG film. The results show that the method enables measurements of the diffusion coefficient through the polymer film. Neither the stirring rate nor the concentration of hGH influenced the diffusion coefficient. The diffusion coefficient of hGH through degraded PLG films was 5.0.10(-13) m(2)/s, which is in the range that could be expected, i.e., several orders of magnitude smaller than its the diffusivity in pure water. The reproducibility was good, considering the dynamic properties of PLG, i.e., the difference in diffusion coefficients, at, for example, different stages of degradation and for different compositions of PLG, is expected to be much higher. The variation is probably also present in PLG films used for controlled-release formulations. Although the PLG film contains a large amount of water, a considerable time elapsed before pores of sufficient size formed and diffusion through the film started. In two-component diffusion experiments, the difference in diffusion rate did not correspond to the difference in molecular weight of the solutes, indicating a size exclusion effect. This method can be used to study the effect of changes in the formulation specification. By studying the change in the diffusion coefficient through the degradation process of PLG, or similar polymers, a better understanding of diffusion and, thus, also release mechanisms can be obtained.
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| 5. |
- Höckerfelt, Mina Heidarian, et al.
(författare)
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Dry mixing transformed micro-particles of a drug from a highly crystalline to a highly amorphous state
- 2009
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Ingår i: Pharmaceutical development and technology (Print). - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 14:3, s. 233-239
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the degree of mechanical activation of particles due to mechanical straining without subsequent breakage has been studied. Griseofulvin micro-particles of about 2 mum in size were mixed with glass beads (proportion 1:99) in a tumbling mixer. After a series of mixing times, ranging from 2-96 hours, samples were withdrawn and the particle size and the degree of crystallinity were assessed. The mixing process gave no detectable change in particle size. The degree of disorder of the drug particles increased with mixing time and highly amorphous particles were obtained after about 24 h of mixing. The results thus indicate that particles can be completely activated by mechanical treatment without a parallel size reduction of the particles. It is suggested that the activation is caused by repeated deformation of the particles, gradually transforming the crystalline state into an amorphous state.
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| 6. |
- Kaunisto, Erik, et al.
(författare)
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Drug dissolution rate measurements - evaluation of the rotating disc method.
- 2009
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Ingår i: Pharmaceutical Development and Technology. - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 14, s. 400-408
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Tidskriftsartikel (refereegranskat)abstract
- Dissolution rate measurements are important to understand the behaviour of drugs or drug formulations. Many methods for measuring dissolution rates are available and a good choice should be based on method limitations as well as drug characteristics. In the present study the rotating disc method was critically evaluated for dissolution rate measurements, using aspirin and benzoic acid as model substances. Existing theory for the rotating disc was compared with experiments and a computational fluid dynamics (CFD) model simulating the USP vessel. Simulations showed that it is possible to predict mass transfer controlled drug release rates within the laminar flow regime. Mass transfer coefficients obtained from the CFD model were in better agreement with experimental data than those obtained from existing theory. It was concluded that the hydrodynamic boundary layer controlling release rates was in reality thicker than existing theory would suggest.
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| 7. |
- Larsen, Bjarke Strom, et al.
(författare)
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Using dextran of different molecular weights to achieve faster eeze-drying and improved storage stability of lactate dehydrogenase
- 2019
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Ingår i: Pharmaceutical development and technology (Print). - : Taylor & Francis. - 1083-7450 .- 1097-9867. ; 24:3, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- Freeze-drying of protein formulations is frequently used to maintain otein activity during storage. The freeze-drying process usually quires long primary drying times because the highest acceptable drying mperature to obtain acceptable products is dependent on the glass ansition temperature of the maximally freeze-concentrated solution -g). On the other hand, retaining protein activity during storage is lated to the glass transition temperature (T-g) of the final eeze-dried product. In this study, dextrans with different molecular ight (1 and 40kDa) and mixtures thereof at the ratio 3:1, 1:1, and 1:3 /w) were used as cryo-/lyoprotectant and their impact on the stability the model protein lactate dehydrogenase (LDH) was investigated at evated temperatures (40 degrees C and 60 degrees C). The dextran rmulations were then compared to formulations containing sucrose as yo-/lyoprotectant. Because of the higher T-g values of the dextrans, e primary drying times could be reduced compared to freeze-drying with crose. Similarly, the higher T-g and T-g of dextrans relative to crose led to benefits during storage which was shown through improved otection of LDH activity.
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| 8. |
- Lastow, Orest, et al.
(författare)
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Low-voltage electrohydrodynamic (EHD) spray drying of respirable particles
- 2007
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Ingår i: Pharmaceutical Development and Technology. - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 12:2, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Spray drying is a widely used process to produce pharmaceutical powders. In traditional spray drying, the particle size distribution is wide and not well controlled. Using EHD atomization for spray drying offers a possibility to tailor the particle size and morphology. In conventional EHD spray drying, the generated particles are charged and need to be discharged to avoid Rayleigh breakup. Discharging adds complexity to the process and eliminates the possibility to collect the powder using an electric field. The present work describes a novel EHD spray drying setup based on a low-voltage nozzle. The low-voltage nozzle imparts moderate charge to the droplets, which makes discharging unnecessary. The charged particles can be controlled and collected by using an auxiliary electric field. The EHD spray dryer has been characterized in terms of particle size, particle morphology, process output, and yield. The size distribution of the generated particles is very narrow. Both porous and completely spherical particles can be produced. The yield of small-scale bench-top equipment was 20%, which is similar to the yield of a small-scale conventional spray dryer. The effective output with five nozzles was 75 mg/hr of dry powder. Because of the repelling forces associated with the unipolarly charged droplets, the number of nozzles can be increased without risking coalescence.
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| 9. |
- 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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| 10. |
- Nordström, Josefina, et al.
(författare)
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Degree of compression as a potential process control tool of tablet tensile strength
- 2011
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Ingår i: Pharmaceutical development and technology (Print). - : Informa UK Limited. - 1083-7450 .- 1097-9867. ; 16:6, s. 599-608
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Tidskriftsartikel (refereegranskat)abstract
- The current view on the development and manufacturing of pharmaceutical preparations points towards improved control tools that can be implemented in pharmaceutical manufacturing as a means to better control end product properties. The objective of this paper was to investigate the relationship between tablet tensile strength and the degree of bed compression in order to evaluate the suitability of assessing the straining of the powder bed during tableting as a process control tool of tablet tensile strength. Microcrystalline cellulose was used as powder raw material and subjected to wet granulation by different procedures to create agglomerates of different physical and compression properties. The produced agglomerates thus showed a large variation in compressibility and compactibility. However, in terms of the relationship between the degree of compression and the tablet tensile strength, all agglomerates gathered reasonably around a single general relationship. The degree of compression hence appears to be a potential valuable process control tool of the tablet tensile strength that may enable the use of an adaptive tableting process with improved product quality consistency.
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