ECTS: 15
Faglige nøgleord: lægemiddelformulering, miceller, fysisk farmaci
Antal Studerende: 1-2
Vejleder: René Holm
Beskrivelse: There is general agreement on the importance of patient centricity in drug development within the industry and in particular age-appropriate drug products for oral delivery was the starting point of the considerations also provided that the majority of medication prescribed and taken are still conventional tablets or capsules (e.g. Burke et al., 2019; Campbell and Vallejo, 2015; Page et al., 2016; Stegeman, 2012; 2018; Drumond, 2020; Timpe et al., 2020; Hanning et al., 2016; Menditto et al., 2020). Patient centricity can be described as the recognition of the needs of an individual patient or distinct patient populations to form the focal point in the overall design of a medicine including the targeted patients’ physiological, physical, psychological, and social characteristics (Stegeman, 2016; Drumond, 2020). From a drug development perspective this can be translated into a patient centric drug development, which will be the process of identifying the comprehensive needs of individuals or the target patient population and utilizing the identified needs to design pharmaceutical drug products that provide the best overall benefit to risk profile for that target patient population over the intended duration of treatment (Stegeman, 2016; Drumond, 2020). Both U.S. Food and Drug administration (FDA) (FDA, 2023) and the European Medicines Agency (EMA) (EMA, 2017) have initiated patient centric design initiatives and both agencies have guidance’s and reflection papers in development on the topic stressing its importance.
From a drug delivery perspective an interesting perspective was brought forward as a part of the FDA's Patient Focused Drug Development initiative in 2014, the FDA released a report on the Voice of the Patient affected by Human Immunodeficiency Virus (HIV). This report focused on the perspectives of HIV patients regarding current HIV management approaches and the symptoms they experience due to HIV or its treatment. The patients emphasized the practical advantage of a once-daily drug and single pill regimens in terms of medication adherence. However, many patients also expressed that an ideal treatment goes beyond once a day, thereby reducing the frequency of dosing, i.e., a long acting injectable (LAI) (FDA, 2014). Similar voicings have been reported from schizophrenic patients (Blackwood et al., 2020).
For water soluble compounds, three main approaches are used for generation of LAIs – microspheres, implants (degradable and non-degradable) and in situ forming gels. The number of biocompatible cosolvents are limited, e.g., DMSO, NMP and low molecular weight PEG, and the compounds should preferably be soluble in these in order to fit the formulation platform. It is, however, possible to market a formulation where the API is a suspension in the cosolvent, as seen for the highest dose of Eilgard (Gonella et al., 2022). Also, for a compound to fit into an in situ forming gel based on PLGA, it would need to be stable at the lower pH that will be formed in the gel, as also discussed above with PLGA microspheres. The application of in situ forming gels therefore have two main obstacles that needs to be optimised from a formulation perspective. Kim et al. (2022) have recently demonstrated that it is possible to improve the solubility of the tuberculosis compound rifabutin in NMP by addition of nonionic surfactants, however, to the best of my knowledge the approach has only been investigated for one compound, i.e. it is not known if this is a general concept that can be applied in the formulation of new in situ forming gels.
The purpose of this project is therefore to investigate of other water soluble compounds will have improved solubility in NMP, DMSO and/or PEG when added non-ionic surfactants.
Metoder: Nogle af følgende anvendes: mølning, partikelstørrelsesmåling og karakterisering vha. laserdiffraktion, XRPD, mikroskopi, rhehologiske målinger.