Daniel Bar-Shalom
Lektor
E-mail: dbs(at)farma.ku.dk
Telefon: 35 33 63 51
Rum 13 - 305a

Easy to swallow formulations for children
Paediatric patients often cannot swallow the dosage forms they need to take because they are not available in age-specific versions. The problem is exponentially amplified in cases where the child’s condition requires multiple medicines.
 Medicines for children are often prepared magisterially. Preparing magisterial combination formulations is problematic as it is difficult to rule out interactions between the different drugs and/or excipients present in the final product.
 In this set of projects, strategies are developed to: (a) avoid interactions, (b) effectibly mask the taste of the medicines and (c) develop age appropriate dosage forms. There is overlap between this and the following set of projects (Dosage forms for the elderly under POLYPHARMACY regimens).

Keywords: dosage form, paediatric patients, polypharmacy
Supervisors: Daniel Bar-Shalom and Jette Jacobsen

Dosage forms for the elderly under POLYPHARMACY regimens
The elderly often are afflicted by a number of conditions each requiring one or more drugs in different schedules. To make things more complicated, aging is often associated with loss of mechanical (“cannot pick up the tablet or open the packaging”) and mental function (“cannot remember if the red ones are once or twice daily, was it morning or evening?”). On top of this, many of those patients have difficulties with the sheer number of tablets and capsules they need to swallow and with the amount of water required to wash them down.
 In this set of projects, strategies are developed to overcome or alleviate the obstacles. There are many aspects to be addressed: formulation, information gathering, behavior of the patients and so on. There is overlap between this and the former set of projects (Easy to swallow formulations for children).

Keywords: dosage form, formulation, polypharmacy
Supervisors: Daniel Bar-Shalom and Jette Jacobsen

Partial coating of Erodible Oral Controlled Drug Delivery Systems
If controlled release is needed and the drug happens to be water soluble and stable in solution, then a diffusion system is probably the best answer. In many cases, however, diffusion systems are not applicable, then Erosion Based systems may be the best answer. In Erodible systems, the rate of release depends on the geometrical form of the unit. We have developed a system where, using conventional coating equipment, we are able to coat tablets but in such a way that areas are left exposed to erosion affording a high degree of control of the erosion as well as of the drug release. The technique is new and many parameters are undefined. We wish to examine the possibility of having pulsatile delivery and zero-order delivery.

Keywords: partial coating, erosion based system, pulsatile delivery, zero-order delivery
Supervisors: Daniel Bar-Shalom and Kaisa Naelapää

Targeted delivery of liposomes to the mid-gut
Liposomes are small lipid vesicles covered by a bilayer of phospholipids, cholesterol, and a smaller amount of other components. They can be used as biocompatible carriers of active components for pharmaceutical purposes. The potential therapeutic benefits of liposome for oral delivery of vaccines and unstable drugs have aroused great interest. Unfortunately, liposomes released in the stomach and at the beginning of the small intestines are affected by bile acids, digestive enzymes and in general, the hostile environment. The small intestine is organized in such a way that different sections have different functions for digestion and absorption of carbohydrates, lipids, and proteins. Most of the enzymatic activities are localized at the upper part of GI tract, i.e. duodenum and upper jejunum. The aim of this project is to identify areas where liposomes are not (or at least less) affected by the enzymes and the bile and, if such areas are found, to design delivery strategies to by-pass the “wrong” segments and deliver to the “right” ones. This project will be in collaboration with a University in the United Kingdom, using innovative tools. Many important drugs, which are poorly absorbed, could benefit from this approach.

Key words: oral administration, drug delivery, target delivery, liposome, innovative tools.
Supervisors: Daniel Bar-Shalom and Huiling Mu

Drug Formulations for Micro Containers
For active pharmaceutical ingredients with low solubility and low permeability advanced drug delivery systems are needed in order to achieve an acceptable oral bioavailability.
We are evaluating the use of micrometer sized containers for drug delivery. The micro containers are fabricated at the Technical University of Denmark and are made of a biodegradable polymer. The advances of the micro containers are that they can target drug delivery to specific regions in the intestine, give a unidirectional release, increase the intestinal permeability and hereby, improve the oral bioavailability. This student project will focus on the absorption of model drugs from the micro containers. This will be accomplished by the use of caco-2 cells and/or the HT29 cell line, which are useful in vitro models for studying the intestinal drug permeability. Feasible ways of placing the micro containers close to the Caco-2 cells will be developed and in such a way that both release and absorption can be studied.

Keywords: Drug delivery system, intestinal absorption, caco-2 cell model
Supervisors: Anette Müllertz, Daniel Bar-Shalom, and Line Hagner Nielsen (Ph.D. Student)