468257 Evaporation of Binary Mixtures and Shell Formation in Spray Dried Droplets

Tuesday, November 15, 2016: 1:58 PM
Continental 5 (Hilton San Francisco Union Square)
Pedro Valente1, Íris Duarte2, Tiago Porfirio3, Xu Liu4, Feng Zhang4 and Márcio Temtem1, (1)R&D Drug Product Development, Hovione FarmaCiência SA, Loures, Portugal, (2)Faculty of Pharmacy, University of Lisbon & Hovione Farmaciência, SA, Loures, Portugal, (3)LAETA, IDMEC, Mechanical Engineering Department, Instituto Superior Tecnico, University of Lisbon, Lisbon, Portugal, (4)College of Pharmacy, University of Texas at Austin, Austin

Evaporation of binary mixtures and shell formation in spray dried droplets

P.C. Valente1, Í. Duarte1, T. Porfirio1, X. Liu2, F. Zhang2 & M.N. Temtem1   

1 R&D Drug Product Development, Hovione Farmaciência S.A, Sete Casas, 2674-506 Loures, Portugal;

2 College of Pharmacy, University of Texas at Austin, U.S.A;

Amorphous solid dispersions (ASDs) of poorly water soluble active pharmaceutical ingredients (APIs) in hydrophilic polymeric matrices are a commonly used strategy to increase the solubility and dissolution rate of oral-dosage forms [1]. However, since the polymer is hydrophilic and the API is poorly water soluble, it is often difficult to find a common solvent for both and a mixture of co-solvents is used instead. Solvent mixtures also offer the possibility of influencing particle morphology and drying rate [2] and have been reported to offer advantages in the solid state drug-polymer miscibility and on the stability of the ASDs [3,4].

To fully explore the potential of spray dried ASDs from co-solvent drug-polymer solutions, a fundamental understanding on the solvent chemistry, droplet composition history throughout drying and its impact on the drug-polymer interaction, stability and phase behavior are required. These mechanisms are, in turn, strongly influenced by the process conditions, such as thermodynamic layout, atomizing characteristics and spray drier geometry.

The focus of the present work lies on the evaporative dynamics of binary solvent droplets and how they are influenced by process conditions. Unlike the single component counterpart, modelling the evaporation of binary mixtures depends not only on the process parameters, but also on the mass (and momentum) transfer within the droplet [5]. For example, if one considers solely the molecular diffusion for solvent mixtures with starkly different vaporization enthalpies, the evaporation rate of each solvent will be proportional to their initial mass fraction and, counter-intuitively, will be independent of the vaporization enthalpies [6].  However, whenever there is a non-negligible relative velocity between the droplet and the surrounding drying gas, the internal circulation within the droplet can lead to a steep increase in the effective mass diffusion rate. The evaporation rate of each solvent will also strongly depend on their vaporization enthalpy (see Figure 1). This leads to the more intuitive case where the more volatile solvent tends to evaporate first.

We show that these two limits lead to dramatically different drying kinetics and can strongly affect the onset of drug/polymer precipitation and shell formation. After shell formation the drying kinetics tend to be strongly modified, highlighting the importance in predicting the onset of shell formation to bound the applicability of the drying models. These two limiting cases of infinitely slow or infinitely fast droplet component diffusion may be used to formulate scalar (0D) evaporation models [5,6]. In practical spray drying situations, both limits can be attained depending on the binary mass diffusion coefficients, atomization characteristics, temperature profile or drying gas flow velocity, to name a few parameters.  These evaporation models are particularly useful when coupled to a numerical solver to predict stability and phase separation of amorphous solid dispersions [7,8] or a numerical solver of the Navier-Stokes equations, commonly denoted as computer fluid dynamics (CFD) [9,10].

We extend the previously developed platform for phase separation prediction of drug-polymer-solvent systems to systems with binary solvent blends in an effort to generalize a screening methodology for ASDs and compare the data against experimental results.

Figure 1: Sketch of various stages throughout the droplet drying history: a) droplet with internal circulation caused by the relative velocity between the droplet and the surrounding gas, b) shell formation and c) the final particle.


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Stability of Naproxen/PVP K 25 Solid Dispersions Prepared by Cosolvent Spray-Drying”, Pharm. Res. 2012, 29, pp. 251-270.

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[7] Duarte, Í., Santos, J. L, Pinto, J. G & Temtem, M., “Screening methodologies for the development of spray-dried amorphous solid dispersions”, Pharm. Res., 2015, 32 pp. 222 – 237, 2015.

[8] Prudic, A., Ji, Y. & Sadowski, G., “Thermodynamic Phase Behavior of API/Polymer Solid Dispersions”, Mol. Pharmaceutics, 2014, 11(7), pp. 2294-2304

[9] Sazhin, S.S et al., “A simplified model for bi-component droplet heating and evaporation”, Int. J. Heat Mass Transfer, 2010, 21 pp. 4495-4505

[10] Maqua, C., Castanet, G. & Lemoine, F., “Bicomponent droplets evaporation: Temperature measurements and modelling”, Fuel 2008, 87(13-14), pp. 2932-2942.

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