Projects / Programmes
Pharmaceutical technology: design, preparation and evaluation of drug delivery systems
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 1.09.00 |
Natural sciences and mathematics |
Pharmacy |
|
| Code |
Science |
Field |
| B740 |
Biomedical sciences |
Pharmacological sciences, pharmacognosy, pharmacy, toxicology |
drugs (biologically active substances), excipients, drug delivery systems, pre-formulation studies, formulation studies, interactions, transport, modelling and simulation, clinical effects, pharmacogenetics, pharmacoeconomics, pharmacoepidemiology
Researchers (47)
Organisations (1)
Abstract
New findings in science and medicine tend to encourage the etiological treatment and disease prevention over the symptomatic treatment. Classical active ingredients, which are mostly small molecules, are more and more replaced by peptide and protein related substances, which are in many cases hydrophilic and metabolicaly unstable. As a result, these drugs can in their unchanged form hardly pass through different physical and biological barriers in comparison to classical drugs. Thus, a development of new methodologies is necessary in order to evaluate the kinetics and mechanisms of the processes that alter the fate of a drug after its application. Furthermore, a development of new drug delivery systems is required for drug targeting.
The purpose of the research in the field of drug delivery systems, regardless of the drug properties, is the introduction of the principle of controlled drug delivery and targeting. In the biological systems, this principle can be applied in two levels; at the site of drug absorption and at the site of drug action. It is generally accepted that only a minor part of the administered drug reaches the site of action. On the other hand, the majority of the drug is equally distributed throughout the body, bound to the non-specific binding sites. Consequently, adverse effects can occur, and in some cases, serious adverse events can happen. Moreover, a constant drug plasma concentration profile does not necessarily provide optimal drug concentration profile at the site of action. For several diseases it was established that the concentration of a drug at the site of action (organ, tissue, or cell) must oscillate in order to achieve the optimal effect according to various physiological rhythms in the body. Therefore, it is urgent to develop »intelligent« delivery systems, in which optimal site of drug delivery and optimal rate and extent of drug release can be adjusted to the instantaneus body requirements. We focus our research to the development of new drug delivery systems and new pharmaceutical excipients, together with the evaluation of their properties, compatibility, and stability and the preparation and design of these systems. Additionally, an emphasis is made on technological processes, investigation of mechanisms of interactions and drug transport in the body, and development of pharmaceutical technological and chemical analytical methods taking into acount also the measures of protecting the environment.
Our research is performed within four interactive sections:
• Evaluation of drugs in models of growing complexity: classification into BCS (Biopharmaceutical Classification System); drug transport processes and metabolism in relation to the genotype; kinetics and mechanism of ADME processes (Absorption, Distribution, Metabolism, and Elimination); bioavailability (at the site of action); stability; assays of drug and metabolite (degradation products) levels in heterogeneous (technological and biological) systems; relationship between pharmacokinetics, pharmacodynamics and drug effects.
• Integration of drugs into delivery systems:
pre-formulation drug research (small and large molecules - hidro/lipophilicity, solubility, permeability, stability, crystallinity, surface energy, primray, secondary, tertiary and quaternary structure),
excipients (drug carriers, absorption enhancers, bioadhesives, bioconjugates, lioprotectants, antioxidants, antiadsorbents, antiaggregation agents - physicochemical properties, rheological properties, functional properties, biocompatibility, biodegradability.
formulation drug research – the appropriate choice of excipients for a selected drug, considering the purpose of drug formulation; preparation and design of micropheres/microcapsules, microtablets, pellets, nanoparticles and liposomes with controlled time and site drug release and for different types of application.
• Evaluation of drug delivery systems in models of growing complexity: development of e
Significance for science
This research program can be viewed as a part of contemporary scientific trends in the field of development and evaluation of new safe and effective medicines with the purpose to increase the effectiveness of therapy. Different approaches have been used and their correlations evaluated using chosen model drugs, thus enabling their implementation on the classical low molecular as well as on the new protein drugs. New techniques of particles design were developed that will enable the preparation of colloidal and larger particles of uniform properties, which will assure the processibility in the delivery systems production and high quality of final products. With the development of delivery systems like nanoparticles the efficacy of the therapy might be increased significantly and drugs’ adverse effects decreased. The results of our research work gave us important information about interactions between different macromolecules (polymers and proteins) and showed how to apply the rules valid in natural biological systems (molecular interactions, spontaneous conformation, biological recognition, cell processes) for the preparation of new drug delivery systems. The possibilities how to circumvent the limitations and take the advantages of protein drugs when incorporating them in delivery systems were explored. The contemporary scientific trends are followed also in the field of studying LADME processes to identify those critical physico-chemical and biological parameters that influence the safety and efficacy of medicines. The experimental models of diversified degree of complexity which were developed in accordance with the goal of our researches are of key importance. Our aims were followed considering all processes to which the drug is exposed after different modes of application. With the development of in vitro tests, which will enable us to describe the processes of drug release and absorption in in vivo conditions after fasted or fed administration, a significant contribution to further development of BCS system will be given and by experimental approaches for description and prediction of presystemic metabolism one of its main deficiencies will be clarified. Physiological parameters were introduced in the dissolution models to give common applicative approach additional scientific dimension and the results of permeability studies enable us a new insight in the mechanisms of mucosal transport of all studied types of drugs. Pharmacokinetic-pharmacodynamic models combined with the methods of population pharmacokinetics help us to identify the reasons for variability in pharmacokinetics, pharmacodynamics and consequently in clinical outcomes. By the use of this technique, the introduction of appropriate procedures before the start of therapy, like avoidance of drug interactions, assessment of genetic polymorphism of transport and metabolic systems, consideration of demographic and clinical-biochemical factors, will be proposed. These studies represent most interesting scientific trends in the process of drug dosing optimization, especially if they are combined, as in our case, with monitoring economic and humanistic outcomes.
Significance for the country
The results of the proposed research program are important for the Slovenian pharmaceutical industry as well as for the Slovenian health care system, which have to follow the modern regulatory requests (EMEA, FDA) for introducing the new technologies and application routes which will assure safe, effective and qualitative drug products and their rational use. Peptides and protein drugs are connected with high specificity, potency and effectiveness in small doses which will have a great impact on the human therapy in the near future. However, their use in the clinical praxis is more or less limited because of the unacceptable biopharmaceutical properties. These properties are a consequence of large molecular weight, hidrophylicity, complex and labile structure and reduce the use of already approved drugs to the parenteral route. This therapy is dealing with frequent dosing, additionally systemic adverse/toxic effect, lower patient compliance and higher costs. All these shortcomings are the driving forces for the pharmaceutical research regarding the development of new drug delivery systems, especially nanosystems. Slovenian pharmaceutical industry is able, due to its high technological level, to implement knowledge developed in this program into the pharmaceutical products with a very high added value. Proposed research program includes also some new technology strategies which mean challenge for the Slovenian process technology industry as well. The optimized technology processes together with the quality of the input ingredients, drugs and excipients, represent imperative for the quality of the drug products. Inside of the program also the aspects of the rationality in the energy and the materials use are considered and implemented. Proposed research program will also assure the knowledge which is important for sustainability of Slovenian health care systems in the fields of drug usage and utilization. Pharmacoepidemiological and pharmacoeconomic studies are included in wider context of health economics and are therefore of national importance.
Most important scientific results
Final report,
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Most important socioeconomically and culturally relevant results
Final report,
complete report on dLib.si
