Keeping an eye on the quality of Ocular Delivery Products using Texture Analysis

Treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving ophthalmic, optic, dermal, oral cavity, and anorectal tissues.

Ocular drug delivery is an interesting and challenging opportunity for pharmaceutical development. 

The eye is protected by a series of complex defence mechanisms, which usually result in poor bioavailability of drugs administered via the ocular route. These include tear production and the blinking reflex in addition to short residence time and reduced drug permeability. The drug bioavailability can be enhanced either by providing prolonged/sustained delivery to the eye or by facilitating transcorneal penetration. 

Texture Analysis in Action: the Powder Compaction Rig

Powder Compaction Rigs:
Low Tolerance (left); High Tolerance (right)

The Stable Micro Systems POWDER COMPACTION RIG is available in two variants.

The High Tolerance Powder Compaction Rig (A/PCRS) is suited to high force applications where the punch/die clearance is critical; this fixture is auto-aligned using a universal adapter.

The Low Tolerance Powder Compaction Rig (A/PCR) is suited to other powder compaction applications such as assessing granule friability, where the punch/die clearance is less critical.

The use of Texture Analysis in Medical Device Development

Texture Analysis, which has long been used by the pharmaceutical, food and cosmetic
industries, is now increasingly being used to evaluate properties of medical devices. 

Texture analysis refers to properties such as firmness, adhesiveness, cohesiveness, tackiness, swelling/absorption, in addition to relaxation behaviour, fatigue and brittleness. For many of these tests, standard methods lag behind product development. 

Regulatory agencies including the FDA have used the TA.XTplus Texture Analyser to evaluate medical devices. In addition, the patent literature increasingly relies on texture analysis to validate claims. 

Read on for more examples of the application of texture analysis to the future of medical devices...

Texture Analysis in Action: the Rice Extrusion Rig

The RICE EXTRUSION RIG (HDP/RE) allows the determination of rice kernel resistance to extrusion after cooking according to ISO 11747.  

The standard is the outcome of inter-laboratory testing and was prepared by the ISO/TC34 Technical Committee for Cereals and Pulses.  

The sample is tested after cooking (parboiled or not parboiled) under specified conditions. A small sample is placed in the testing cell of the rig. 

Texture Analysis in Action: the Tablet Disintegration Rig

The TABLET DISINTEGRATION RIG* (A/TDR)

A thorough analysis of disintegration behaviour is vital for the formulation of new fast-melt tablets (FMTs) to ensure reliable and consistent drug release.

The tablet or wafer has to be resilient enough to endure manufacturing and shipping, yet release sufficient disintegrants to deliver an optimum dissolution rate. The Tablet Disintegration Rig facilitates reliable assessment of the mechanical properties of FMTs.

Texture Analysis in Action: the Ice Cream Scoop and Ice Cream Cone Support Rig

Two of our test attachments have been designed specifically for use in the development of frozen confectionery.

The ICE CREAM SCOOP (A/ICS) is used to measure the scooping resistance of ice cream, and other similar samples which can be formed into a self-supporting block.

A tilt-table is mounted on to the base of the Texture Analyser and the scoop positioned onto the load cell.

Ensuring consistent quality in Rectal Delivery Products

Although administration via the peroral route is the most commonly targeted goal of new drug and dosage form research and development, oral administration is not always feasible or desirable. 

The potential for oral dosage form development is severely limited for active agents that are poorly absorbed in the upper gastrointestinal (GI) tract and unstable to proteolytic enzymes. Some agents cause local stomach or upper GI irritation or require doses in excess of 500mg. Additionally, treatment of some diseases is best achieved by direct administration near the affected area, particularly with diseases involving anorectal tissues. 

Although oral administration can be used for drugs targeted for some of these diseased tissues, exposure of the entire body compartment to the administered drug is inefficient and can lead to undesired adverse effects. 

Texture Analysis in Action: the Wire Cutter

One of our simpler test attachments is the WIRE CUTTER (A/BC). 

This device incorporates a standard 0.3mm diameter wire, which is supported on a frame enabling it to cut through a 500g block of butter or similar self-supporting block-form sample. 

It can be used to measure the firmness of butter, ice cream or margarine and the consistency of cheese by measuring the force to drive the wire through the sample.

Texture Analysis in Action: the Abrasion Test Rig

The ABRASION TEST RIG (HDP/ATR) analyses the frictional properties of a wide range of materials such as sandpaper, dental abrasive strips and flexible nail files.

This enables manufacturers to highlight strengths, weaknesses and variations in product lines and materials.

Prior to performing the test, a sample of the abrasive material is held in place in a self-tightening grip. 

Texture Analysis in Action: Friction Testing

Stable Micro Systems offers two options for Friction Testing attachments.

The HORIZONTAL FRICTION SYSTEM (A/HFS) comprises a support leg and levelling feet which are fixed to the Texture Analyser, so that the assembly can be laid in a horizontal position. 

A platform is fitted to the base on which a friction sled, which is attached to the loadcell, is constrained to slide over the sample.

Additional load may be provided by adding weights positioned centrally on the sled. This arrangement offers the advantage of measuring sliding friction in both directions and also during cycling. Typical applications include films, creams and packaging.

Comparison of ease of spreading of
two moisturising creams

Testing the Mechanical Strength of Coronary Stents

Vascular stents are commonly used as a minimally invasive way to treat stenosis in arteries and improve blood flow to the heart, kidneys, brain and legs. 

Due to the challenging service environment that stents face in vivo, the radial stiffness of a stent is critical to its function of keeping the arteries open and eliminating abrupt closure. Measurements and reporting methods of a stent’s radial stiffness both assist industry in the development of new stent designs and allow regulatory authorities to better evaluate these designs.

Texture Analysis in Action: the Sachet/Tube Extrusion Rig

The SACHET/TUBE EXTRUSION RIG (A/STE) is a device which extrudes the contents of sachet and tube style packaging.

It has been designed to allow manufacturers of pharmaceutical, cosmetic and personal care products to quantify the ease of removal and application of products such as ointments, creams and gels.

The rig positions the product vertically between two rollers, clamping the closed end with a grip at the top. The grip then pulls the sachet/tube upwards through the rollers, forcing the contents out whilst measuring the force required.

Product developers can analyse changes in a product’s consistency throughout its shelf-life and adapt formulations accordingly whilst also enabling manufacturers to assess the suitability of packaging material and its construction.

Texture Analysis in Action: the Mucoadhesion Rig

The MUCOADHESION RIG* (A/MUC) 
 
Mucoadhesion is the process by which a drug delivery device is designed to stick to a part of the gut or other mucosae, thus delivering drug to a precise site in the body for an extended period.

This gives more effective treatment of some diseases and can also protect drugs from some of the harsh conditions in the body.

Texture Analysis in Action: the Powder Flow Analyser

The POWDER FLOW ANALYSER (PFA/PL) is an accurate and reliable method of measuring the flow characteristics of powders.  

It can be rapidly fitted to a Stable Micro Systems plus series Texture Analyser, enabling manufacturers to assess and avoid typical problems such as batch and source variation of ingredients, caking during storage/transportation and problems with discharging from hoppers or bins.

The Powder Flow Analyser is supplied with library tests so operators can start testing quickly and conveniently after straightforward installation and calibration. Users can, however, fully program the instrument to carry out slicing, shearing, compressing, compacting and aerating cycles in any combination.

Texture Analysis in Action: the Bilayer Tablet Shear Rig

BILAYER TABLET SHEAR RIG* (A/BTS)

Bilayer systems typically contain an immediate-release component in one layer and the extended-release component in the other layer.

However, the development and production of quality bilayer tablets is not without issues such as layer separation. The Bilayer Tablet Shear Rig provides the means to assess this problem. 

Measurement of shear force to separate
components of a bilayer tablet

Texture Analysis in Action: the Dobrascycyk-Roberts Dough Inflation System

Most dough rheological measurements are performed at rates and conditions very different from those experienced during baking. 

Conventional oscillation shear rheological tests usually operate at small strains of up to 1%, while strain in gas cell expansion during proof can be several hundred percent. Furthermore, most rheological tests are carried out in shear, whereas most large strain deformations in dough (i.e. sheeting, proofing, and baking) are extensional in nature. 

The deformation around an expanding gas cell during proof is biaxial extension – deformation in the cell wall material surrounding an expanding gas bubble. Therefore, any rheological tests on dough that seek to predict baking performance should be carried out under conditions close to baking expansion.

Texture Analysis in Action: Leather Testing

One specialist area where texture analysis has had a considerable impact is LEATHER TESTING.

Stable Micro Systems offers a range of test rigs specifically designed to enable accurate and repeatable tests on all types of leather samples. 

Our application designers have worked closely with end user companies and institutions to ensure that the equipment achieves the best possible results.

Texture Analysis in Action: the Avery Adhesive Test

THE AVERY ADHESIVE TEST
(using probe P/1S)

Over recent years, one objective of the Pressure Sensitive Adhesive industry has been to identify a single, standard, reproducible test to easily measure the tack of a PSA. 

As a result, experiments with probe adhesive testers of various designs have taken place. Some of these testers have measured the tack force, that is, the maximum force recorded during the debonding of the probe from the adhesive.

Others have suggested measuring the tack as a function of energy dissipation during the debonding process. Because of this ambiguity, the probe tack testers have not provided a better definition of tack than other conventional tack performance tests such as loop tack, rolling ball tack, etc.

Texture Analysis in Action: the Hair Combing Rig

The HAIR COMBING RIG (A/HCR) has been developed to assist manufacturers in the development of more effective conditioning agents.

It is well known that conditioning shampoos and hair conditioners are used to provide a variety of benefits to hair: they reduce the combing force, enhance the gloss, confer smoothness and antistatic properties and they improve the manageability of the hair.

Texture Analysis in Action: the Tape Unwinding Rig

The TAPE UNWINDING RIG (A/TUR) allows the measurement of unwind adhesion – the force required to unwind the tape from the roll. 

This attachment consists of a spool, with heavy duty ball bearing, the mount for which screws to the test platform. A standard tensile grip secures the loose end of the tape reel and the adhesive strength may be measured as the grip tries to peel the tape from the reel.

The rig allows the measurement of unwind adhesion – the force required the tape from the roll.