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Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin

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Abstract

In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively. A matrix of the dry emulsions was composed at a fixed ratio mixture of mannitol and HPMC. Tween 20 was used in low amounts as the primary emulsion stabiliser. To facilitate process optimisation, a DoE surface response design was used to study the influence of formulation and process parameters on the particle size distribution, powder bulk properties, emulsion reconstitution ability, drug stability and process yield of spray-dried products. Two-fluid nozzle geometry was identified, studied and confirmed to be important for most product critical quality attributes. Models obtained after the study showed acceptable coefficients of determination and provided good insight in the relationship governing the process and product characteristics. Five model optimised products showed adequate process yield, suitable particle size distribution, good reconstitution ability and improved dissolution profile, when compared to a non-lipid-based tablet and the pure drug. However, the obtained dry emulsion powders exhibited poor flow character according to the Carr index. The optimised product was further analysed with NMR during lipolysis to gain insight into the species formed during digestion and the kinetics of their formation.

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Acknowledgements

The authors thank the Faculty of Pharmacy, University of Ljubljana (UL), Slovenia, for supporting this study and the University of South Australia (UNISA) for accepting the PhD student and for the possibility to conduct lipolysis studies.

Funding

Financial support for the research project was provided by the Slovenian Research Agency under contract number P1-0189.

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  1. Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia

    Mitja Pohlen, Zoran Lavrič & Rok Dreu

  2. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    Clive Prestidge

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  1. Mitja Pohlen
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Correspondence to Rok Dreu.

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Pohlen, M., Lavrič, Z., Prestidge, C. et al. Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin. AAPS PharmSciTech 21, 119 (2020). https://doi.org/10.1208/s12249-020-01651-x

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