Drying behaviour and visualization of surfactants after co-spray drying of surfactant-stabilized aqueous suspensions.

Surfactants are widely used in many industries as dispersants or flocculants for suspensions. As the addition of low concentrations of surfactant is sufficient to execute their effect, they barely alter the formulation composition. In this research it was examined whether surfactants, in particular polysorbate 80 (PS80), were suitable as suspension stabilizers for co-spray drying of drug-filler combinations. Therefore, their drying behaviour at different process and formulation settings was studied and mapped by means of fluorescently labelled PS80. Co-spray drying of 10% w/w aqueous suspensions stabilized with 0.1% w/w PS80 resulted in excessive loss of sticky powder in the conical lower part of the drying chamber and the powder conveyor ducts. Up to 16% of powder was lost in the first transporter (i.e. the first part of the conveyor ducts). The amount of powder deposited in the first transporter, and by extension the stickiness of the recovered powder, was correlated with the presence of PS80 on the surface of the spray dried particles. Redistribution of free surfactant molecules during droplet drying depended on the process and formulation parameters. Enrichment of PS80 at the particle surface was most pronounced after co-spray drying of liquid feedstocks with low suspended fraction at process conditions favouring rapid droplet drying.

Viscosity of API/fatty acid suspensions: Pitfalls during analysis.

This article describes how to obtain reliable data during rheological analysis of active pharmaceutical ingredient/fatty acid suspensions. These materials are specifically used for prilling, an innovative pharmaceutical technique for the production of a multiparticulate dosage form. Nevertheless, presented guidelines are applicable for a wide range of pharmaceutical suspensions. Reliable rheological results can only be obtained when being aware of artefacts, such as a non-continuous medium, sedimentation, apparent wall slip and protrusion flow. To comply with the continuum hypothesis at high phase volumes (≥25% w/w), the required gap-to-particle-size ratio may be larger than the generally accepted 10:1 ratio. Reproducible flow curves that are not disturbed by sedimentation during sample analysis can be obtained faster by varying the shear rate stepwise from high to low values. While apparent wall slip (at low shear rates) can be prevented via serrated instead of smooth plates, protrusion flow (at high shear rates) during measurements with serrated plates results in non-reliable data. Therefore, in general, high viscous suspensions with yield stress can be analysed with serrated plates, while low viscous suspensions without yield stress should be analysed with geometries having smooth surfaces. By following these guidelines, accurate rheological properties of pharmaceutical suspensions can be obtained.

Prilling of API/fatty acid suspensions: Screening of additives for drug release modification.

Current study screened additives which could modify the drug release from prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension, without negatively influencing the processability and/or stability of the formulation. Therefore, 11 additives (i.e. emulsifiers, pore-formers and FA-based lubricants) were added in a 20% concentration to a paracetamol/behenic acid formulation. Two additives, Kolliphor® P338 and P407 provided complete drug release in less than 1 h, as their thermoreversible gel formation resulted in a disintegration of the prills. Lower Kolliphor® P338 or P407 concentrations (2.5-10%) resulted in a complete but slower drug release in 24 h as the prills no longer disintegrated and the release mechanism was dominated by pore-formation. Prills with a robust drug release profile (i.e. independent of pH and surfactant concentration of the dissolution medium) were obtained after the addition of ≥5% Kolliphor® P338 or P407 to the FA-based formulation. Based on a 6-month stability study, it was concluded that Kolliphor® P407 was a suitable additive to modify the drug release profile of API/FA suspension-based prills when formulations were stored below 25 °C at low relative humidity.

Prilling of API/fatty acid suspensions: Processability and characterisation.

Current study evaluated the processability and characteristics of prills made of an active pharmaceutical ingredient/fatty acid (API/FA) suspension instead of previously studied API/FA solutions to enlarge the application field of prilling. Metformin hydrochloride (MET) and paracetamol (PAR) were used as model APIs while both the effect of drug load (10-40%) and FA chain length (C14-C22) were evaluated. API/FA suspensions were processable on lab-scale prilling equipment without thermal degradation, nozzle obstruction or sedimentation in function of processing time. The collected prills were spherical (AR ≥ 0.898) with a smooth surface (sphericity ≥ 0.914) and a particle size of ±2.3 mm and 2.4 mm for MET and PAR prills, respectively, independent of drug load and/or FA chain length. In vitro drug release evaluation revealed a faster drug release at higher drug load, higher API water solubility and shorter FA chain length. Solid state characterisation via XRD and Raman spectroscopy showed that API and FA crystallinity was maintained after thermal processing via prilling and during storage. Evaluation of the similarity factor indicated a stable drug release (f2 > 50) from MET and PAR prills after 6 months storage at 25 °C or 40 °C.