Quality control of pharmaceutical products using rotational viscometry

Syrup is a concentrated, aqueous solution of sugar or a sugar substitute with or without flavors. It contains one or more active ingredients in the solution. Such a solution is called a syrup if the sucrose concentration is 85 %, which also prevents bacterial growth.^[5]

The viscosity of cough syrup should be preferably as high as possible but it should still be drinkable in order to smoothly flow past the digestive tract. To evaluate the flow behavior of cough syrup with a rotational viscometer it is useful to perform a speed/shear rate ramp test and analyze the flow behavior with e.g. the mathematical regression model “Power Law”. With this mathematical model two parameters can be obtained: the consistency index and the flow index.^[6]

1. Consistency index k: This parameter represents the product’s viscosity at one reciprocal second, which means at rest in the bottle.
2. Flow index n: This parameter determines the flow behavior of the cough syrup. When n < 1 the product shows shear-thinning behavior. This means that the apparent viscosity decreases as the shear rate increases. The closer n is to 0, the stronger the shear-thinning behavior of the material is. When n > 1 the product shows shear-thickening behavior. Its apparent viscosity increases as the shear rate increases. When n = 1 the product shows Newtonian flow behavior. This means the viscosity is independent of the shear rate.

To guarantee customer satisfaction and consistent quality from batch to batch the flow index and consistency index need to be properly adjusted.

Example: 7.5 mL of a cough syrup sample were analyzed with a rotational viscometer using a double-gap measuring system at different shear rates (Figure 1). According to the mathematical model “Power Law” the syrup has a relatively high viscosity of 94.93 Pa·s at rest (1 s^-1). Also during swallowing the preferred high viscosity of the syrup does not change as it shows Newtonian flow behavior of n = 1 (flow index).

The viscosity of ointments and lotions, for example, has an impact on several stages in the production: It must be possible to pump them, pack them, and squeeze them out of the packing easily, and also to apply them on the target body areas. To be able to forecast the viscosity during production and at application, the viscosity at different speeds/shear rates has to be determined with a rotational viscometer. Ointments have to show shear-thinning flow behavior, because the viscosity has to decrease when a force is applied, e.g. during squeezing it out of a tube or applying it to the skin. In order to prevent liquids like ointments from flowing out of the tube when no force is applied, the yield point has to be analyzed. On rotational viscometers, the yield point is often calculated from flow curves measured with a linear increase of the speed using mathematical regression models. Once the desired emulsion and emulsifiers have been chosen, a consistency that provides the desired stability and yet has the appropriate flow characteristics must be attained. Generally, an increase in viscosity minimizes creaming, rising, or sedimentation of particles. A change in the globule size or number or migration of emulsifying agent during aging may be detected by a change in viscosity. Further, flocculation of oil-in-water emulsions results in an immediate increase in viscosity.^[7]

Example: After carrying out a speed ramp test the yield point of an ointment was analyzed using the mathematical regression model Herschel-Bulkley (Figure 2). The Herschel-Bulkley model gives the product’s yield stress (τo) as well as the product’s flow index and consistency index.^[8] The tested ointment does not flow immediately out of the tube. 90.75 N/m² need to be applied on the tube to make the ointment flow. Based on this data, formulators are able to modify the ingredients accordingly. Once a formulation is established, multi-point tests and e.g. analyses using the Herschel-Bulkley model can be performed for quality control to check batches before and after processing.