Ongoing projects

Research in formulation of poorly watersoluble active compounds in PLGA Nanoparticles using spray-drying technology. 01/10/2017 - 30/09/2021

Abstract

The poor water-solubility of new active pharmaceutical ingredients (API) is a true challenge for formulation experts. Before an API can reach the systemic circulation and reach the target site of action, orally-taken drugs need to dissolve first in the gastrointestinal fluids. The use of organic solvents in high-throughput screening of new API's, as well as the structure-activity related research, often results in candidate-molecules with an extreme lipophilicity and high molecular weight and consequently a poor water-solubility. In this project, different formulation technologies will be screened to increase the bio-availability of these API's. This project focusses on an innovative technology, the spray-drying of nanoparticles (NP's), in comparison with 3 more conventional formulation approaches (cyclodextrine-complexes, amorphous systems and PolyLactic-co-Glycolic Acid (PLGA)-nanoparticles). Embeded in the Antwerp Drug Discovery Network of the UA, the Laboratory of Pharmaceutical Technology (LPTB) is well situated to bridge the Medicinal Chemistry research activities with the LMPH in vivo-modeling expertise. This allows the evaluation of the full potential of new medicinal compounds in an in vitro and in vivo setting. Last year, the applicants' laboratory supported several other UA labs requesting formulation assistance with their poorly water-soluble compounds.

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Past projects

Formulation and processing of probiotic bacteria in a solid oral dosage form for pharyngeal delivery. 01/01/2017 - 02/11/2020

Abstract

Respiratory infections know a high morbidity. Nowadays, patients are treated with over-thecounter products such as decongestives and expectorants. There is also an overuse of antibiotics, which leads to antibiotic resistance. Therefore, a new therapy, based on microbiomemanipulation, is imposed. This research will focus on the improvements for this new therapeutic strategy. The human body consists of many microorganisms lives in symbiosis with each other, resulting in beneficial effects for both. Pathogens can disturb this symbiosis. The homeostasis can be restored by probiotic formulations. They will reinforce the innate immunity. It is the aim of this research to develop a solid oral dosage form for the pharyngeal delivery of probiotic bacteria, which can prevent and treat respiratory infections. Mechanical stress during compression can damage the bacteria, which can result in therapy failure. The aim of this research is to protect the bacteria by choosing the correct formulation and process parameters. This research will be combined with detailed microbiological analysis. The stability of the formulation will be investigated by stability tests. Finally, the efficacy and safety of the formulation will be determined by in vitro tests. Successful results can lead to clinical studies on humans and to new businesses. This can result in a medical and economical progress..

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Research in Formulation and Processing of Probiotics in Buccal Dosage Forms. 01/10/2015 - 31/12/2016

Abstract

In case of many nasopharyngeal diseases, such as otitis media, acute and chronic sinusitis and pharyngitis, patients frequently resort to self-medication using over-the-counter products. Often, clinical data is lacking to support the use of decongestive, expectorantia or nasal salt solutions and relapse is frequent. On the other hand, (ab)use of antibiotics is linked with the resistance-issue. Main idea of this project is that local buccal or nasal sprays or lozenges, in which Lactobacillus species are formulated, could enhance the existing therapies. Many nose and throat disease conditions also show a microbial imbalance between enhanced numbers of pathogenic microbes versus decreased number of beneficial macrobiotics. Ultimately, dosage forms containing probiotics might be the preferred upper-airway-therapy over antibiotics-usage. In this project, fundamental formulation and process research will be conducted, to support and in preparation of (pre)clinical studies. The application of spray drying as innovative manufacturing technology for probiotic dosage forms, has many advantages such as excellent control over process parameters and over powder characteristics. The lyophilization-technology is applied as the reference drying technique. The influence of excipients and additives in the formulation will be investigated. They might have a protective effect during the processing, as well as during stability and at moment of reconstitution into the final dosage form. Secondly they will determine the powder particle properties, important for lozenge-formulation. Finally, their effect on adhesion of the formulation to bucal epithelial cells , might be advantageous in terms of local residence time and efficacy . Probiotic cell viability is evaluated in function of the spray drying process parameters. Final goal of this project is a buccal lozenge containing probiotics, having a sufficient efficacy and stability. This project fits perfectly in an on-going IOF-SBO program in collaboration with the UA research lab of Prof. Dr. Sarah Lebeer (Bio-engineering Sciences).

Researcher(s)

  • Promotor: Kiekens Filip
  • Co-promotor: Claes Ingmar
  • Fellow: Byl Eline

Research team(s)

The influence of probiotic watercontent and wateractivity in spray-dried nasopharyngeal and buccal formulations. 01/02/2014 - 31/12/2014

Abstract

This project investigates how the critical formulation and process parameters influence the zeta-potential and the wateractivity in nasal/buccal sprays and lozenges of spray-dried probiotics, in particular with Lactobacillus rhamnosus species. The link between wateractivity, absolute water content and cell viability will be investigated immediately after production and in a stability study.

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Research to establish specific product and process characteristics from an innovative technological process to produce inserts loaded with peptides/proteins. 01/12/2011 - 30/11/2012

Abstract

In the research group Pharmaceutical Technology and Biopharmacy a new method of preparation for ocular dosage forms loaded with peptides and/or proteins has been developed. In this proof-of-concept study, product characteristics and process parameters from the invention will be optimized. The physico-chemical characteristics of the intermediate product and final product from the innovative technological process are evaluated together with optimization of the mixing conditions. The data are needed for submission of a patent with clear defined and specified claims.

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Development and evaluation of pharmaceutical forms loaded with a therapeutic peptide used for ocular purposes 01/01/2011 - 31/08/2011

Abstract

In this project several ocular delivery systems for controlled delivery of peptides will be examined by means of a factorial design. In vitro and in vivo studies will be performed to select the appropriate candidates. First the peptide cyclosporine is selected for the development of the concept. Afterwards, the technological platform can be used to develop optimal formulations for other specific therapeutic peptides.

Researcher(s)

  • Promotor: Van Den Plas Dave

Research team(s)

Development, evaluation and optimization of ocular drug delivery concepts for the use in dry eye syndrome and retinal disorders. 01/09/2009 - 31/08/2011

Abstract

Several ocular drug delivery concepts will be developed, characterized in vitro and ex vivo and evaluated in vivo. First the peptide cyclosporine is selected for the development of the concepts. Afterwards, the most promising formulation will be further developed for retinal disorders with a specific peptide.

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Nanomaterials to administer medicine. 01/01/2007 - 31/12/2011

Abstract

The scientific aim of the research consortium is to try to understand why some nanocarrriers loaded with biological active molecules (e.g. proteins, antisense oligonucleotides, RNAi, plasmid DNA) are successful and elicit a biological effect in certain cells but fail in other cell structures. It is of fundamental importance to gain insights in these topics. But this is only possible when the problems are tackled with a multidisciplinar team from different prospectives (e.g; biological, pharmaceutical, physicochemical, biophysical, ...)

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Drug targeting of Leishmania parasites using colloidal carriers. 01/10/2005 - 30/09/2006

Abstract

The research consists of the formulation and optimalisation of colloidal carriers (liposomes and nanoparticles) in order to target leishmania parasites in the host cells with a broad spectrum and potent saponine. The influence of the technological parameters of the preparation procedure on the physicochemical properties and the endocytosis of the carriers will be investigated. The therapeutic effect in vitro and in vivo will be evaluated.

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Development and optimization of biocompatible colloidal carriers (liposomes and nanoparticles) for targeting the intracellular parasite Leishmania donovani. 01/05/2005 - 31/12/2006

Abstract

The research consists of the formulation and optimalisation of colloidal carriers (liposomes and nanoparticles) in order to target leishmania parasites in the host cells with a broad spectrum and potent saponine. The influence of the technological parameters of the preparation procedure on the physicochemical properties and the endocytosis of the carriers will be investigated. The therapeutic effect in vitro and in vivo will be evaluated.

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Optimisation of the therapeutic activity of PLGA nanoparticles loaded with antibiotics (ciprofloxacin) for the treatment of infections of the outer eye. 01/01/2005 - 31/12/2005

Abstract

The aim of the project is to optimise the therapeutic activity of PLGA nanoparticles loaded with ciprofloxacin for the treatment of outer eye infections. I) The nanoparticles will be coated with bioadhesive polymers to improve the interaction with the mucus layer of the tear film in order to extend the residence time at the eye surface. The targeting to different rnicroorganisms will be realised by using cationic polymers. The physical characteristics of the prepared nanoparticles will be determined. 2) The antimicrobial activity of ciprofloxacin loaded and coated PLGA nanoparticles against Pseudomonas aeruginosa, Staphylococcus aureus and Chlamydia trachoma tis will be evaluated. Herewith, the effect of coating on the drug release kinetics and the antimicrobial activity will be studied. 3) The interaction of the nanoparticles with the previously mentioned test microorganisms m culture medium, embedded in biofilrns or located intracellular will be determined.

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Biodegradable and bioerodible ocular dosage forms with sustained release. 01/10/2004 - 30/09/2006

Abstract

To improve the bioavailability of ophthalmic drugs biocompatible and biodegradable colloidal carriers with sustained release will be developed and compare to bioadhesive minitablets. The formulation of PLGA nano or microparticles will be optimised by using factorial design in order to gain insights in the various parameters influencing the physical properties of the particles prepared. Particles will be characterized by measuring the size, zetapotential, drug load and release rate before and after freeze-drying and sterilisation. Moreover the external and internal structures of the particles will be examined. Afterwards the muco or bioadhesion of the carrier will be improved by coating of the particles with (cationic) polymers in order to lengthen the precorneal residence time. Finally from the most promising preparations the in vivo tolerance and release rate from (coated) PLGA particles and minitablets will be investigated.

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In vivo evaluation of bio-erodible minitablets for prolonged ocular drug delivery. 01/01/2004 - 31/12/2004

Abstract

Bioerodible sterilised minitablets (6 mg and diameter 2 mm) used as ocular drug delivery system, will be evaluated in humans. First of all, a clinical study comparing conventional eye drops and optimised minitablets containing ciprofloxacin (3%, w/w) will be performed in healthy volunteers to prove the effectiveness of the minitablet for sustained ocular delivery of ciprofloxacin. Secondly, after in vitro screening of new formulations for sustained release over a longer period of time, an in vivo evaluation of minitablets composed of the formulation with the required sustained release properties and containing fluorescein will be performed in healthy volunteers. A fluorophotometer will be used to measure the tearfilm-cornea concentrations of fluorescein at regular time intervals in a non-invasive way. Finally, if the in vivo study with fluorescein indicates the suitability of the minitablets for obtaining sustained release for a longer period of time, this formulation will be selected to prepare minitablets containing vancomycin and gentamicin and its physicochemical and technological properties will be evaluated in vitro. Consequently these minitablets will be evaluated in the healthy eye of hospitalised patients treated with fortified eye drops for bacterial keratitis. The tear concentrations of the drugs in both eyes will be determined by a validated HPLC method.

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Optimisation of bioadhesive minitablets containing an antifungal drug for ocular purpose. 01/10/2003 - 30/09/2004

Abstract

An interesting strategy to increase the bioavailability of ophthalmic drugs is the development of a sterile, bioadhesive minitablet. The minitablets consist of biocompatible, hydrophilic polymers, which form after hydratation by lacrimal fluid a gel. The drug molecules diffuse slowly out of the gel and exert their therapeutic effect at the surface of the eye or after absorption into the eye structures. The influence of the composition of the minitablets, their mode of preparation (direct compression or dry granulation), compression forces used during tabletting and the sterilisation (gamma radiation) on the physical characteristics of the minitablets (friability, tensile strength, swelling behaviour) and the release of the active drug molecule will be examined. The influence of the shelf life conditions (temperature and relative humidity) on the physicochemical properties of the minitablets will be evaluated.

Researcher(s)

Research team(s)

Biodegradable and bioerodible ocular dosage forms with sustained release. 01/10/2002 - 30/09/2004

Abstract

To improve the bioavailability of ophthalmic drugs biocompatible and biodegradable colloidal carriers with sustained release will be developed and compare to bioadhesive minitablets. The formulation of PLGA nano or microparticles will be optimised by using factorial design in order to gain insights in the various parameters influencing the physical properties of the particles prepared. Particles will be characterized by measuring the size, zetapotential, drug load and release rate before and after freeze-drying and sterilisation. Moreover the external and internal structures of the particles will be examined. Afterwards the muco or bioadhesion of the carrier will be improved by coating of the particles with (cationic) polymers in order to lengthen the precorneal residence time. Finally from the most promising preparations the in vivo tolerance and release rate from (coated) PLGA particles and minitablets will be investigated.

Researcher(s)

Research team(s)

Colloidal drug delivery systems for ophthalmic use. 01/01/2001 - 31/12/2003

Abstract

The aim of the research project is the formulation of colloidal carrier systems and the study of the parameters influencing the physical properties of the nanoparticles, the stability of the preparaion and the release of model drugs from the nanoparticles prepared. To formulate the carrier systems biocompatible and biodegradable compounds will be employed such as polysaccharides, proteins, phospholipids and polyesters. Besides the classical solvent evaporation and precipitation methods, preparations without organic solvents but using high homogenisation pressures at the temperature required will be performed. Coating of the colloidal particles with bioadhesive polymers could be applied to improve the residence time at the eye surface. The various parameters which could influence the physical properties of the carriers such as the charge and chainlength of the polymers, concentration ratio of the various compounds, addition of excipients, pressure and temperature will be evaluated by means of factorial design. The characterisation of the carrier sytems prepared includes the measurement of the mean particle size and polydispersity, zetapotential, drug loading efficiency. Ocular dosage forms must be sterile, therefore the stability during autoclaving will be examined or the validation of an aseptic preparation method will be performed. The stability of the preparations during storage under various conditions will be evaluated. The in vitro release of model drugs from stable carrier systems will be measured under standard conditions, which simulate the in vivo situation. The influence of tear composition (normal and pathologic) will be studied.

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