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How to measure and analyse the texture of food, cosmetics, pharmaceuticals and adhesives.

Tuesday 14 June 2016

Novel Oral Dosage Forms : Capsules


Liquid-fill formulation is one of the fastest growing sectors of the drug delivery market, increasing at a rate of 30% per annum. 

This is due to the number of highly potent chemical and biological drugs moving through development pipelines today – particularly for cancer treatments – but in fact, encapsulated products, such as fish oils, have long been popular as vitamin, health and performance supplements. 

Unlike many other forms, capsules mask taste and odour and allow for quick speed-to-market, yet they require less excipient. Their versatility allows for a multiplicity of branding options in terms of colour, size and printing/graphics. And of course, they are smooth, easy-to-swallow and are suitable for almost any dosage strength.

Many new entrants in the supplements market are liquid-based, particularly the so-called fat-burners or muscle-mass-gaining capsules in the field of sports nutrition. Liquid formulas release rapidly into the digestive system, allowing the active ingredients to provide the best possible benefits. However, this may require an adaptation to the capsule make-up, especially for lipid-based formulations. 

The modification of capsule construction to accommodate its content with optimum shelf life and consumer mouthfeel properties will require an assessment of its physical performance. The brittleness, hardness and flexibility of gel capsules and their resilience to variable storage and handling conditions should be considered, along with any potential effect the contents may have on the mechanical properties of the capsule itself.

Filled to bursting point?
Typical capsule burst test
using a 2mm cylinder probe
and shatter screen

While the comfort factor of soft gel capsules is not to be underestimated, such media are primarily used to contain water- or oil-based formulations where a failure in the encapsulation could be catastrophic. 

The robustness of a soft gel capsule can be determined via a particular compression test known as the Bursting Test. This measures the maximum force that a capsule can be subjected to and establishes whether there is a weak point in the gel film or capsule seal.
It is important to use a rig that will prevent the capsule from rolling and shifting when pressure is first applied. Frequently a plate with a small indentation is all that is needed.
Some choose to have the seal of the capsule run around the capsule so that it neither is in contact with the holding plate nor the probe and the probe starts the compression of the capsule at 90° to the seal. In this case, a small cylinder probe (e.g. 2-3mm diameter) would be used to puncture the capsule. 

Some say the seal is the strongest point and they want to test the bursting point of the film and thus have the capsule seal in a vertical orientation so that the probe applies the force directly against the seal line. In this case, a cylinder probe larger than the capsule is used to compress the sample. For safety purposes, a Shatter Screen is strongly recommended as a safety measure in a “dramatic” test such as this.

Capsules can be tested under different conditions to assess the effects of temperature, humidity, storage and handling, but the integrity of the capsule may also be affected by its contents. Simple compression tests on gel capsules do not always adequately predict which formulations may result in failures related to brittleness, and hence those drugs which are suitable for hard or soft gel encapsulation.

Measuring Brittleness/Flexibility
Capsule Tensile Rig fitted to
the TA.XTplus Texture Analyser

The simplified manufacture process of hard gelatine capsules and their ability to withstand higher filling temperatures is attractive to many manufacturers. 

However,  the introduction of certain types of liquid, such as hydrophilic solvents, to hard capsules can often affect the mechanical properties of the shell, causing them to become brittle or soften. If the texture of a capsule is compromised, it may not be able to withstand handling and storage, resulting in fillings leaking from the capsule.

As effects are likely to be progressive, only displaying very small changes initially, compressive tests may not be able to distinguish the anomalies adequately. The capsule tensile rig is designed to help identify subtle degradation, providing valuable information which can be used to avoid subsequent capsule failure. For example, manufacturers can identify the effect of liquid filling on the strength and stability of capsules and therefore reformulate liquid type or capsule material accordingly.

Comparison of tensile strength
of gelatine capsules using
the Capsule Tensile Rig

Prior to testing, the filling of the capsule is removed and one half of the empty shell is mounted to the Capsule Tensile Rig, a separating rod fixture, on the TA.XTplus texture analyser. Vertical movement of the upper rod is then applied until the capsule is split apart, while Exponent software records the force required to do so. 

This test highlights three important parameters; elastic stiffness (if a linear region on the graph is present), tensile force and elongation at break point. A reduction in elastic stiffness and tensile strength occurs when capsules become softer and therefore show a tendency to fail. 

The test allows manufacturers to investigate the effects of fillings on the mechanical strength of the capsule shell and identify changes that may impact their stability and long-term performance.

MicroCapsules/Gel Beads

Alginate beads (typically sodium or calcium) are widely used for slow release of water soluble chemicals. 

They are used for products such as drugs, pesticides and fertilizers; they present a suitable carrier matrix because they are natural, biodegradable, biocompatible, and hydrophilic polymers suitable for the entrapment of water soluble drugs. The excellent gelation ability has further led to the use of alginates for entrapment of cells within gel beads. Cells so entrapped maintain viability and metabolic function and are capable of secreting a variety of protein products into the external medium.  

For all these applications, appropriate performance of the microcapsules is critically dependent on the properties of the capsular membrane. For example, an oral delivery microcapsule intended for GI delivery can be disrupted by many different means during its intestinal passage; it may be fractured by enzymatic action, chemical reactions, heat, pH, diffusion, mechanical pressure and other related physiological and biochemical stresses.
The safety of microcapsules is even more important when live cells are intended for use in the intestinal system by oral administration. This is because the live cells must be protected during the encapsulation process and microcapsules must reach the GI intact. 

In addition, the survival of the live cells during their passage must be ensured. Thus, the microcapsule membrane must be provided with sufficient permeability for nutrients, and secretion and excretion products, to pass through, yet prevent the entry of hostile molecules or cells from the host, for example, products of the host's immune response, which could destroy the encapsulated bacterial cells. The problems inherent with oral delivery, therefore, have made the goal of oral delivery of live bacterial cells very challenging. 

The mechanical and permeability properties of alginate gels vary greatly with the composition of the alginate and thus the controlled release potential. As such, the assessment of varying gel concentrations, M:G ratios and ion concentrations on the mechanical properties, and their effect on release of the active ingredient, are a vital part of determining the optimal gel bead composition.

Most companies that make gel beads of different types only measure the peak force to burst the beads. Commonly the distance at which the bead bursts, or the bead’s resilience or relaxation characteristics are not measured.

Measuring Resilience

A small diameter cylinder probe is positioned directly above the bead’s surface and the test proceeds to typically compress the bead to a distance of 25% of its detected height at 0.5mm/s. 

Resilience test

The graph shown illustrates a typical bead compression curve highlighting the regions of interest for calculation. The area (as shaded in the graph) between anchors 1 and 2 highlights the measurement of the energy of compression of the bead, reflecting the bead’s work of resistance to the compression or firmness. The energy quantified as the area between anchors 2 and 3 is the resilient work that the bead returns to the probe on its withdrawal. 

If the compression and withdrawal speeds are set to the same speed, then the Area 2:3/Area 1:2 calculates the bead’s percentage of resilience. 

The distance travelled between anchors 1 and 2 quantifies the distance that the sample was depressed to attain 25% strain, while the distance measurement between anchors 2 and 3 reflects the distance the bead springs back. If, for example, Distance 2:3/Distance 1:2 is 1.0 then springiness would be quantified as 100%.

Measuring Burst Characteristics
Burst test

The burst characteristics of beads can be measured using the same probe. 

Adjustment of the compression distance to 90% strain, so as to further compress the beads past their burst point, is the only necessary modification to the method. The maximum force is recorded and used as a measure of Burst Strength/Force. The graph [M] shows examples of differing burst points of 5 bead products tested using this method.

Relaxation test

Measuring Relaxation

A third test that should be of interest is a relaxation test. 

The test can be accomplished by simply changing the resilience test option to Hold Until Time. Under this test, the probe descends to the target distance (e.g. 25% strain) and then stays there until the targeted time has elapsed. Typically the calculated parameters [N] are the Firmness and either the % of Energy Retained or % of Energy Lost after the target time has elapsed.

A summary of how to perform texture analysis on the alternatives to traditional tablet-form medications using a TA.XTplus Texture Analyser can be viewed in this video...

We can design and manufacture probes or fixtures for the TA.XTplus texture analyser that are bespoke to your sample and its specific measurement.

Once your measurement is performed, our expertise in its graphical interpretation is unparalleled. Not only can we develop the most suitable and accurate method for the testing of your sample, but we can also prepare analysis procedures that obtain the desired parameters from your curve and drop them into a spreadsheet or report designed around your requirements.

For more information on how to measure texture, please visit the Texture Analysis Properties section on our website.

TA.XTplus texture analyser with bloom jar The
TA.XTplus texture analyser is part of a family of texture analysis instruments and equipment from Stable Micro Systems. An extensive portfolio of specialist attachments is available to measure and analyse the textural properties of a huge range of food products. Our technical experts can also custom design instrument fixtures according to individual specifications.

No-one understands texture analysis like we do!

To discuss your specific test requirements click here...

Watch our video about testing of materials

 The Role of Texture Analysis in Pharmaceuticals

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