Comparison of the rheological behaviour of ready-to-use suspension vehicles and formulated for patients with swallowing disorders

Introduction:
Two ready-to-use vehicles for oral suspension are widely used: Orablend^© (OB) and Inorpha^© (InO). They are time saving by eliminating the formulating time but may not be optimal in terms of composition (excipients of interest) or viscosity. Viscosity of suspensions influence their physical stability. The objective of this work was to study the rheological behavior of these vehicles and the physical stability of suspensions produced with them, to compare them i) with each other ii) with a vehicle formulated containing 0.4% xanthan gum (XG) as a thickening agent without any excipient of interest.

Materials/methods:
Six vials of suspension were made by dispersing the same amount of control powder (with a controlled granulometric homogeneity) in each vehicle. Amount of XG in the formulation was determined to reach the same viscosity of OB as a reference. The rheological behavior was studied using a HAAKE MARS III rheometer and a cone (C60/1°) – plane (P20) geometry. An ascending and descending ramp of rotational shear stress was applied to 1.5 ml of each suspension. Sedimentation kinetics on days 0, 30, 60 and 90 was assessed with TurbiscanLAB^® using transmission profiles at 0° and backscattering at 135°, with scans at a wavelength of 880 nm at 25°C. For InO, an additional measurement over 24 hours on D0 was made. Resuspension was studied with a 30 ml of suspension in each vehicle after 90 days of sedimentation. The number of inversions necessary for visually homogeneous resuspension was determined with 8 independent operators.

Results:
InO shows Newtonian behavior while OB and XG show non-Newtonian, shear-thinning behavior. The average viscosity at 57s-1 of each suspension was (mean [sd]) 14,05 [0.08]cP; 72,33 cP [1.29]; and 80,1 cP [0.41] for Ino, OB and XG respectively. The fraction of light backscattered at the cell’s bottom increases rapidly in InO showing formation of a powder pellet during the first 24 hours. A pellet forms for XG since D30 and slowly increase until D90. No pellet formation was observed in OB until D90. Number of inversions necessary to obtain visual homogeneity and total resuspension was (median [min-max]) 43 [20-100], 3 [1-17] and 129 [36-324] for InO, OB and XG respectively.

Conclusion:
OB offers the best physical stability. On the contrary, InO shows Newtonian behaviour and sedimentation is fast. However, its low viscosity allows easier resuspension than for XG, which is thicker, in which a pellet is also formed. InO used alone seems incompatible with good physical stability and safe administration in patients with dysphagia (viscosity must be greater than 51 cP). Moreover, OB is the best candidate but contains excipients of interest, which must be taken into account when administering in paediatrics. Based on these observations we can conclude that there is a need for new compounding vehicle.

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