Jankovic, Sandra
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Towards a better understanding of solid dispersions in aqueous environment by a fluorescence quenching approach
Solid dispersions (SDs) represent an important formulation technique to achieve supersaturation in gastro-intestinal fluids and to enhance absorption of poorly water-soluble drugs. Extensive research was leading to a rather good understanding of SDs in the dry state, whereas the complex interactions in aqueous medium are still challenging to analyze. This paper introduces a fluorescence quenching approach together with size-exclusion chromatography to study drug and polymer interactions that emerge from SDs release testing in aqueous colloidal phase. Celecoxib was used as a model drug as it is poorly water-soluble and also exhibits native fluorescence so that quenching experiments were enabled. Different pharmaceutical polymers were evaluated by the (modified) Stern-Volmer model, which was complemented by further bulk analytics. Drug accessibility by the quencher and its affinity to celecoxib were studied in physical mixtures as well as with in SDs. The obtained differences enabled important molecular insights into the different formulations. Knowledge of relevant drug-polymer interactions and the amount of drug embedded into polymer aggregates in the aqueous phase is of high relevance for understanding of SD performance. The novel fluorescence quenching approach is highly promising for future research and it can provide guidance in early formulation development.
Lipophilicity and hydrophobicity considerations in bio‐enabling oral formulations approaches – a PEARRL review
Objectives This review highlights aspects of drug hydrophobicity and lipophilicity as determinants of different oral formulation approaches with specific focus on enabling formulation technologies. An overview is provided on appropriate formulation selection by focussing on the physicochemical properties of the drug. Key findings Crystal lattice energy and the octanol–water partitioning behaviour of a poorly soluble drug are conventionally viewed as characteristics of hydrophobicity and lipophilicity, which matter particularly for any dissolution process during manufacturing and regarding drug release in the gastrointestinal tract. Different oral formulation strategies are discussed in the present review, including lipid‐based delivery, amorphous solid dispersions, mesoporous silica, nanosuspensions and cyclodextrin formulations. Summary Current literature suggests that selection of formulation approaches in pharmaceutics is still highly dependent on the availability of technological expertise in a company or research group. Encouraging is that, recent advancements point to more structured and scientifically based development approaches. More research is still needed to better link physicochemical drug properties to pharmaceutical formulation design.