Viscosity and rheology of topical semisolids

Viscosity is a property of fluid that depends on the conditions of measurement. An outlook by Dr Phalguni Naik, Application Support Manager, Brookfield Advanced Application Laboratory

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Dr Phalguni Naik

Creams, gels and suspensions comprise the largest part in the pharmaceutical industry. Viscosity and rheology are monitored for quality control, consistency and pharmacopoeial regulations during formulation of ointments and gels. However, material’s viscosity is not a single value, rather viscosity is a property of fluid that depends on the conditions of measurement, for example, the rate of deformation (shear rate), etc.

The value of Newtonian fluid is one in which the viscosity does not change with shear rate and time. The best example of Newtonian liquid is water. For non-Newtonian fluid, viscosity is a function of shear rate and time and may increase or decrease with respect to shear rate and time. An example of non-Newtonian liquid is viscosity of topical semi-solids.

Topical suspensions are liquid preparations that contain solid particles dispersed in a liquid medium intended for application to the skin. Some suspensions are classified as lotions, ointments, gels, creams and pastes. Viscosity decreases with increase in shear rate (rubbing action means increased shear rates); while viscosity regains after shearing stops. This is called ‘Thixotropy’ and can be evaluated from thixotropic loop by cone plate rheometers with 1-2 ml of samples.

Rheological properties such as viscosity and thixotropy of semi-solid dosage forms can influence their drug delivery. Viscosity may directly influence the diffusion rate of the drug.

Therefore, the product flow behaviour must be monitored at the time of its application. This also helps to monitor batch-to-batch consistency. Most topical semisolids, when applied on the surface of the skin, show non-Newtonian behaviour. The structures formed within semisolid drug products during manufacturing can show a wide range of behaviours, including shear thinning, viscosity, thixotropy and irreversible or reversible structure damage.

Brookfield R / S Cone Plate Rheometer with CFR 21 compliance is a good option to measure viscosity and rheology of topical semisolids.

A number of rheological properties play an important role in determining how a material behaves as it moves from storage to handling environment and vice-versa. For example, the force or stress required to initiate flow (yield point) of fluids and semi-solid products plays a significant role in the shelf-life, storage, transfer, packaging and end-use performance of those materials.

Why to measure rheology properties?

The success of the product formulation in the market depends on the end-use performance. The correct formulation of these ingredients allow topical gels and creams to easily flow out of the container (yield stress), which ensures no sedimentation of solid particles during storage, stability (zero shear viscosity) and good spreadability (shear-thinning) on the surface. This helps in uniform coating of the gels on the skin surface for medicinal use and controlled drug delivery. The modulus gives information on stiffness of the product.

All these quality parameters are related to rheology properties, determined by Cone Plate Rheometer. Based on this rheometric technique, one could predict quality monitoring and behaviour of topical semisolids in the end use performance.

Experimental

The data was obtained by Brookfield R/S Cone Plate Rheometer on viscosity and flow behaviour / rheology properties of topical semisolids.

The sample required is 2 ml.

Result: DI Thixotropy

The test setting was done as follows:

Step 1: Shear Rate ramp 0 to 200 / second for 60 seconds.
Step 2: Shear Rate ramp from 200 to 0 / second Result: 68.9224 [Pa / S].

Thixotropic fluids are generally dispersions; but when they are at rest, they construct an intermolecular system of forces and turn the fluid into solid, thus, increasing the viscosity.

In order to overcome these forces and make the fluid turn into a liquid again and which may flow, an external energy strong enough to break the binding forces is needed. Thus, as above a yield stress is needed.

Once the structures are broken, the viscosity is reduced when stirred until it receives its lowest possible value for a constant shear rate. The viscosity of thixotropic fluids is time dependent, i.e. once shearing is stopped and the fl uid is at rest, the structure will be rebuilt.

This will inform about the fluid possibilities of being reconstructed.

D.II. Viscosity and yield stress

The yield stress is important for pharma products in determining the shelf life, stability and the ease of application for the end-use performance.

Yield stress is defined as the minimum force (Stress) required to initiate flow and can be measured on Brookfield Controlled Stress Rheometers model RS Cone Plate.

Controlled stress Rheometer like Brookfield R/S Plus Cone Plate Rheometer provides a more sensitive measure of this yield stress. The yield stress is related to the level of internal structure in the material which must be destroyed before flow can occur. This is very important to design optimum torque for dispensers and dosing pumps to increase the process efficiency.

Rheology of gels

Pharma and cosmetic gel materials range in consistency from fluid to solid. Semisolid products are the most difficult materials to characterise rheologically because they combine both liquid and solid properties within the same material. The majority of pharma materials are ointments, creams, pastes and gels — all semi-solids.

To understand these complex flows, commercial medical gels, shampoos and cough syrup were tested using the Controlled R/S Cone Plate Rheometer.

Differentiation among different formulation of gels

This is important for the physical performance of the product when used by the consumer. Most ointments are intended to be thick when standing to prevent them from flowing away from the intended area of use. High viscosity at near zero shear rate characterises this behaviour; thus determining the yield stress value quantifies this desired property. Ointments are also engineered to be easy to apply when rubbed. This is known as shear thinning behaviour. Both characteristics of yield and shear-thinning can be easily characterised using only a small volume of 1 ml of the sample with Brookfi eld R/S Cone Plate Rheometer.

Brookfi eld R/S Rheometer with cone spindle CP 75-1 enables low to high shear rate measurements with only 0.5 ml of sample material. The temperature control of the plate is easily accomplished by connecting to circulating water bath.

However, a continuous shear rate programmed viscosity test clearly demonstrates significant differences between the two. The entire measurement time was 6.5 minutes. While both samples exhibit shear thinning behaviour, sample 1 showed a significant loss of viscosity as a result of shearing action, while sample 2 showed minor viscosity loss. Loss of viscosity due to shearing action is termed thixotropy. Such tests allow the pharma manufacturer to adjust formulations to consistently achieve the desired product performance.

Conclusion

Thus, it can be seen that Controlled Stress Rheometers like Brookfi eld R/S Cone Plate Rheometer is capable of measuring and comparing rheology properties of pharmaceutical gels and topical semi-solids in a very short time.

Abbreviations

CFR = Code of Federal Regulation
cP = Centi-Poises
Pa.s = Viscosity in Pascal. Seconds [Pa.s = 1000 cP]
R / S= Shear Rate / Shear Stress