| 1. |
- Dahlberg, Carina, et al.
(author)
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Surface composition and contact angle relationships for differently prepared solid dispersions
- 2008
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 70, s. 478-485
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Journal article (peer-reviewed)abstract
- Solid dispersions are promising drug delivery forms which offer the possibility to disperse a hydrophobic drug in a hydrophilic matrix and thereby improve the dissolution behavior and the bioavailability of the drug. One important aspect and a prerequisite in understanding the drug dissolution mechanism from solid dispersions is a better analytical monitoring of the solid dispersion surface properties, such as powder surface composition and water adsorption properties. In this paper, we have considered chemical and structural surface analysis data for solid dispersions processed by spray drying or roto-evaporation and compared these data with information obtained by contact angle measurements. Firstly, we establish the usefulness and suitability of X-ray photoelectron spectroscopy (XPS) for determination of surface chemical composition and scanning electron microscopy (SEM) for determining the structure of solid dispersions composed of different types of carriers, drugs and drug concentrations. Secondly, we measure contact angles of solid dispersions to describe wettability, to finally establish a link between the surface chemical composition, the powder structure and the wetting behavior. These experimental methods offer a rapid screening tool for the selection of carrier, drug concentration and/or process in early development. In addition, they provide a useful tool for investigating structural aspects of solid dispersions which have intrinsic relevance for drug dissolution and stability.
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| 2. |
- Fransén, Nelly, et al.
(author)
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Development and characterisation of interactive mixtures with a fine-particulate mucoadhesive carrier for nasal drug delivery
- 2007
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 67:2, s. 370-376
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate whether mucoadhesive interactive mixtures can be created using carrier particles in a size range appropriate for nasal administration, i.e. 10–50 μm. We also used theoretical models to investigate if homogeneity measurements can be used to evaluate the formation of interactive mixtures containing carrier particles in this size range. Sodium starch glycolate (SSG) was used as carrier material and sodium salicylate (SS) as the model fine-particulate drug. The size ranges of SSG particles and amounts of SS were varied to find the smallest carrier particle size and highest amount of drug that still resulted in an interactive mixture. Visual inspection of the mixtures by scanning electron microscopy showed that interactive mixtures could be formed with carrier particles as small as 30 μm and containing up to 4% (w/w) of SS. Comparisons with theoretical models highlighted the difficulties of using homogeneity measurements to determine if interactive mixtures were formed. The measured coefficients of variation (CV) for the amount of drug in the samples were low and inferior mixtures were associated with only a slight increase. It was thus concluded that mucoadhesive interactive mixtures can be created in an appropriate size range for nasal administration, but that visual inspection of these mixtures is initially necessary to confirm the formation of an interactive mixture.
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| 3. |
- Klevan, Ingvild, et al.
(author)
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On the physical interpretation of the initial bending of a Shapiro-Konopicky-Heckel compression profile
- 2009
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 71:2, s. 395-401
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Journal article (peer-reviewed)abstract
- The relationship between the natural logarithm of the tablet porosity arc! the applied pressure is used to describe the compression behavior of a powder. Such a relationship, here referred to as a Shapiro-Konopicky-Heckel (SKH) profile, is usually divided into three regions, of which the first often is non-linear. The objective of this work was to address the question of the mechanisms controlling the compression and the bending of the first region of a SKH profile for dense particles. In this paper, the first region was described by the Shapiro General Compression Equation, from which a compression parameter was derived as a measure of the bending. The results indicate that for powders undergoing significant particle rearrangement at low applied pressures, the particle rearrangement is the major cause for the initial bending of the SKH profile. For powders showing limited particle rearrangement, the initial bending is mainly caused by the change in particle diameter due to particle fragmentation. It is concluded that the evaluation of the first region of a SKIT profile in terms of bending may be used to assess particle fragmentation. The SKH profile could hence be a useful tool to describe powder compression behavior in terms of particle fragmentation and particle deformation from one single compression analysis.
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| 4. |
- Unga, Johan, 1976, et al.
(author)
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Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions
- 2009
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 73:2, s. 260-268
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Journal article (peer-reviewed)abstract
- The solid state behaviour of polyethylene glycol 4000 (PEG 4000) and dispersions of a homologous series of parabens (methyl- (MP), ethyl- (EP), propyl- (PP) and butyl- (BP)) were examined and compared to the paraben solubility in liquid PEG 400. Dispersions were prepared by co-melting different amounts of paraben (5-80% (w/w)) and PEG 4000 and were studied using a combination of differential scanning calorimetry (DSC) and small and wide angle X-ray diffraction (SAXD/WAXD). Depending on the concentration of parabens in the dispersions, DSC showed melting peaks from folded and unfolded forms of PEG, a eutectic melting and melting of pure parabens. The fraction of folded PEG increased and the melting temperatures of both PEG forms decreased with increasing paraben content. In an apparent phase diagram of PP-PEG dispersions a eutectic mixture appeared above 5% PP. In addition, a melting peak corresponding to the paraben appeared for dispersion containing more than 60% PP. Similar phase diagrams were shown for the other parabens. The SAXD data and a 1D correlation function analysis revealed that MP and BP were incorporated into the amorphous domains of the lamellae of solid PEG to a higher degree than EP and PP. In addition, the lamellae thickness of PEG and the fraction of amorphous domains increased more for MP and BP compared to EP and PP. BP showed the highest solubility of the parabens followed by MP, EP and PP in both liquid and solid PEG. Furthermore, the thickness of the amorphous domains of the PEG in the different parabens-PEG dispersions could be correlated to the solubility in liquid PEG 400.
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| 5. |
- Zimmermann, A, et al.
(author)
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Adsorption of pharmaceutical excipients onto microcrystals of siramesine hydrochloride: Effects on physicochemical properties
- 2009
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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 71:1, s. 109-116
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Journal article (peer-reviewed)abstract
- A common challenge in the development of new drug substances is poor dissolution characteristics caused by low aqueous solubility. In this study, microcrystals with optimized physicochemical properties were prepared by precipitation in the presence of excipients, which adsorbed to the particle surface and altered particle size, morphology, and dissolution rate. The poorly water-soluble drug siramesine hydrochloride was precipitated by the antisolvent method in the presence of each of various polymeric and surface active excipients. Powder dissolution studies of six of the resulting particle systems showed a significant increase in percent dissolved after 15 min compared to the starting material. A quantitative determination of the amount of excipient adsorbed to the surface of the drug particles proved that only a very small amount of excipient was needed to exert a marked effect on particle properties. The adsorbed amount of excipient constituted less than 1.4% (w/w) of the total particle weight, and thus powders of very high drug loads were obtained. Sodium lauryl sulphate (SLS), hydroxypropyl methylcellulose (HPMC), and hydroxypropyl cellulose (HPC), which exhibited the greatest degree of adsorption, also had the greatest effect on the physicochemical properties of the particles. X-ray Photoelectron Spectroscopy (XPS) analysis of the surface composition and scanning electron microscopy studies on particle morphology suggested that the excipients adsorbed to specific faces of the crystals.
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| 6. |
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| 7. |
- Mosén, Kristina, et al.
(author)
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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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In: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411. ; 64:2, s. 206-211
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Journal article (peer-reviewed)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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| 8. |
- Wadsö, Lars, et al.
(author)
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An improved method to validate the relative humidity generation in sorption balances
- 2009
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In: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 0939-6411. ; 72, s. 99-104
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Journal article (peer-reviewed)abstract
- Sorption balances are instruments in which samples are weighed as they are exposed to a programmed relative humidity (RH). Such instruments are used to measure sorption isotherms and to study solid-vapour interaction. There are different methods to validate the performance of the RH generation in such instruments by charging them with saturated salt solutions and ramping/stepping the RH past the deliquescence RH of the salts. In this paper an improved approach to perform validation is presented where the RH is kept stepwise constant at a quasi-randomly chosen set of RH-values above and below the deliquescence RH. From the rates of change of mass as a function of RH it is possible to calculate the RH at which deliquescence takes place. This alternative method gives similar results as the slow ramp method, but is less sensitive to disturbances and less time consuming.
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