On the role of specific drug binding in modelling arterial eluting stents

In this paper we consider drug binding in the arterial wall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue

Modelling chemistry and biology after implantation of a drug-eluting stent. Part I: Drug transport

Drug-eluting stents have been used widely to prevent restenosis of arteries following percutaneous balloon angioplasty. Mathematical modelling plays an important role in optimising the design of these stents to maximise their efficiency. When designing a drug-eluting stent system, we expect to have a sufficient amount of drug being released into the artery wall for a sufficient period to prevent restenosis. In this paper, a simple model is considered to provide an elementary description of drug release into artery tissue from an implanted stent. From the model, we identified a parameter regime to optimise the system when preparing the polymer coating. The model provides some useful order of magnitude estimates for the key quantities of interest. From the model, we can identify the time scales over which the drug traverses the artery wall and empties from the polymer coating, as well as obtain approximate formulae for the total amount of drug in the artery tissue and the fraction of drug that has released from the polymer. The model was evaluated by comparing to in-vivo experimental data and good agreement was found

Powder Compaction: Compression Properties of Cellulose Ethers

Effective development of matrix tablets requires a comprehensive understanding of different raw material attributes and their impact on process parameters. Cellulose ethers (CE) are the most commonly used pharmaceutical excipients in the fabrication of hydrophilic matrices. The innate good compression and binding properties of CE enable matrices to be prepared using economical direct compression (DC) techniques. However, DC is sensitive to raw material attributes, thus, impacting the compaction process. This article critically reviews prior knowledge on the mechanism of powder compaction and the compression properties of cellulose ethers, giving timely insight into new developments in this field

A National Graduate Research School in Product Realization

The education of Ph.D. students in Sweden has changed during the last decade. Earlier a studentused to take most of his/her courses - which make up about one fourth of the total work in a Ph.D.programme - at the home university and participate in research projects that were based there andmainly involved local researchers. Today’s students are much more active at the national level inboth respects. With support from research foundations, universities have begun to offer joint coursesfor all doctoral students within a specific subject area nationwide, and cooperate in research projectsthat often involve partners not only from several universities but also from industry. There areseveral advantages with this approach to Ph.D. student education. Not only are national resourcesmore efficiently used when courses are offered by the leading researchers and research groups to allstudents in a particular field, the students also get tremendous opportunities to develop personalrelations with each other across institutional borders, something which simplifies and is expected tosubstantially stimulate cooperation between them also after they have graduated and taken uppositions in academia or industry. This paper describes the organisation of and activities in a nationalgraduate research school in product realization which has been in operation since 2003. TheProViking National Graduate Research School offers courses on subjects ranging from customerneeds to ways of manufacturing competitive products. The school is in turn part of the ProVikingprogramme, which is financed by the Swedish Foundation for Strategic Research. The students in theschool also participate in research projects organised by the ProViking programme and withmembers from both academia and industry. One of the authors is the Managing Director of theprogramme and the other is the Director of Studies of the research school

A National Graduate Research School in Product Realization

The education of Ph.D. students in Sweden has changed during the last decade. Earlier a studentused to take most of his/her courses - which make up about one fourth of the total work in a Ph.D.programme - at the home university and participate in research projects that were based there andmainly involved local researchers. Today’s students are much more active at the national level inboth respects. With support from research foundations, universities have begun to offer joint coursesfor all doctoral students within a specific subject area nationwide, and cooperate in research projectsthat often involve partners not only from several universities but also from industry. There areseveral advantages with this approach to Ph.D. student education. Not only are national resourcesmore efficiently used when courses are offered by the leading researchers and research groups to allstudents in a particular field, the students also get tremendous opportunities to develop personalrelations with each other across institutional borders, something which simplifies and is expected tosubstantially stimulate cooperation between them also after they have graduated and taken uppositions in academia or industry. This paper describes the organisation of and activities in a nationalgraduate research school in product realization which has been in operation since 2003. TheProViking National Graduate Research School offers courses on subjects ranging from customerneeds to ways of manufacturing competitive products. The school is in turn part of the ProVikingprogramme, which is financed by the Swedish Foundation for Strategic Research. The students in theschool also participate in research projects organised by the ProViking programme and withmembers from both academia and industry. One of the authors is the Managing Director of theprogramme and the other is the Director of Studies of the research school

Relating solubility data of parabens in liquid PEG 400 to the behaviour of PEG 4000-parabens solid dispersions

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

Influence of polymer molecular weight on the solid-state structure of PEG/monoolein mixtures.

The polar lipid monoolein (MO) and poly(ethylene glycol), PEG, of different molar mass (1500, 4000 and 8000) were melted, mixed and left to solidify at room temperature. Analysis of the solid mixtures by differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS) revealed that a phase separation occurs when MO is present in sufficient amounts. The molecular weight of the polymer determines the amount of MO that has to be added before a separate MO phase can be detected. To further understand this behaviour, the folding of the polymers and the thickness of the amorphous domains within the lamellar structure of PEG were determined by calculation of the one-dimensional correlation function from the experimental SAXS data. It revealed that the presence of MO makes the crystalline domains of PEG 1500, which crystallizes unfolded, increase at the expense of the amorphous domains. PEG 4000 and PEG 8000 obtain a higher degree of folding when the MO content in the mixtures increases. Furthermore, a second form of MO was detected when it phase separated from PEG 1500 and 4000. This behaviour was argued to be due to the secondary crystallization of the PEGs