Final Activity Report Summary - IODDS (Integrated Oral Drug Delivery System)
The overall objective of this Marie Curie project was to validate a new oral drug delivery technology, known as LEDDS™ (Liquid / emulsion drug delivery system) and to establish its potential to allow a broad range of difficult-to-formulate drugs to be made into easily swallow able pills, capsules or tablets. The project has achieved its goals across a broad range of approaches and a range of experiments conducted by MC researchers over the 36 months of the project have successfully validated the path to manufacture of clinical lots, a key milestone in the coordinating company's development. In the process, knowledge was beneficially transferred between participant laboratories.
This Marie Curie Project brought together expertise from four university laboratories in Europe, well known for their capabilities in various aspects of drug delivery, with Sigmoid Pharma Limited, a Dublin-based drug development company. Knowledge was very successfully transferred from the universities to Sigmoid through the Marie Curie programme and contributed to significant development of the LEDDS™ technology. Reciprocally, knowledge of industrial processes, standard operating procedures and good manufacturing principles required for pharmaceuticals were transferred from Sigmoid Pharma to these laboratories. Moreover, the Marie Curie researchers at Sigmoid received training in the above disciplines as well as in technical matters. Researchers coming to Sigmoid also had the opportunity to be involved with the drafting of patent applications working with a qualified patent attorney. In fact, the work led to new patent applications covering novel features of the LEDDS™ platform with a particular focus on the physico-chemical form and properties of minispheres and the capability of LEDDS™ to release drugs into the intestine for local benefit.
Development of oral drug delivery systems is an iterative process. LEDDS™ was at prototype stage at the inception of this Marie Curie project and while much progress had already been achieved, it was necessary to calibrate the prototype with a range of drug types recognising that each drug has distinct characteristics and that the desired behaviour of the drug formulation will also depend on the therapeutic goal (what benefit the pill can be expected to bring). Additionally, it was necessary to establish a laboratory-based way of predicting how the LEDDS™ technology would perform in patients. Moreover, it was necessary to upscale the manufacturing capability for LEDDS™ to permit clinical supplies to be produced and released. Finally, it was necessary to find a means of making much smaller lots (in order to reduce cost) for testing in laboratory models. All these goals were met while an unexpected benefit was the development of an advanced variant of LEDDS™ which became known as SmPill™ (single-multiple pill). Also examined and validated was the extent to which test formulations could be encapsulated and coated with polymers to delay or sustain drug release or to target release to sections of the intestine where drug absorption occurs. Some of this work was published in international journals and conference proceedings.
One particular test drug was successfully formulated and will now be tested clinically. In this case, the therapeutic goal was to design stable minibeads or minicapsules which release the drug into the colon where, for certain diseases, local effect is expected to be most beneficial. The Marie Curie programme has contributed significantly to the progress towards conducting this clinical study bringing significant potential benefits to patients.
The LEDDS™ and SmPill™ technologies are now validated so that it is now possible to consider the reformulation of other known drugs to improve their risk / benefit profile or to make them easier to take e.g. less frequently. In addition, the technologies may also be used to formulate new drugs which cannot otherwise be made orally administrable.
This Marie Curie Project brought together expertise from four university laboratories in Europe, well known for their capabilities in various aspects of drug delivery, with Sigmoid Pharma Limited, a Dublin-based drug development company. Knowledge was very successfully transferred from the universities to Sigmoid through the Marie Curie programme and contributed to significant development of the LEDDS™ technology. Reciprocally, knowledge of industrial processes, standard operating procedures and good manufacturing principles required for pharmaceuticals were transferred from Sigmoid Pharma to these laboratories. Moreover, the Marie Curie researchers at Sigmoid received training in the above disciplines as well as in technical matters. Researchers coming to Sigmoid also had the opportunity to be involved with the drafting of patent applications working with a qualified patent attorney. In fact, the work led to new patent applications covering novel features of the LEDDS™ platform with a particular focus on the physico-chemical form and properties of minispheres and the capability of LEDDS™ to release drugs into the intestine for local benefit.
Development of oral drug delivery systems is an iterative process. LEDDS™ was at prototype stage at the inception of this Marie Curie project and while much progress had already been achieved, it was necessary to calibrate the prototype with a range of drug types recognising that each drug has distinct characteristics and that the desired behaviour of the drug formulation will also depend on the therapeutic goal (what benefit the pill can be expected to bring). Additionally, it was necessary to establish a laboratory-based way of predicting how the LEDDS™ technology would perform in patients. Moreover, it was necessary to upscale the manufacturing capability for LEDDS™ to permit clinical supplies to be produced and released. Finally, it was necessary to find a means of making much smaller lots (in order to reduce cost) for testing in laboratory models. All these goals were met while an unexpected benefit was the development of an advanced variant of LEDDS™ which became known as SmPill™ (single-multiple pill). Also examined and validated was the extent to which test formulations could be encapsulated and coated with polymers to delay or sustain drug release or to target release to sections of the intestine where drug absorption occurs. Some of this work was published in international journals and conference proceedings.
One particular test drug was successfully formulated and will now be tested clinically. In this case, the therapeutic goal was to design stable minibeads or minicapsules which release the drug into the colon where, for certain diseases, local effect is expected to be most beneficial. The Marie Curie programme has contributed significantly to the progress towards conducting this clinical study bringing significant potential benefits to patients.
The LEDDS™ and SmPill™ technologies are now validated so that it is now possible to consider the reformulation of other known drugs to improve their risk / benefit profile or to make them easier to take e.g. less frequently. In addition, the technologies may also be used to formulate new drugs which cannot otherwise be made orally administrable.