Novel Oral Dosage Forms : Films

FILMS

Thin-film drug delivery has emerged as an advanced alternative to the traditional tablets, capsules and liquids often associated with prescription and OTC medications. 

Similar in size, shape and thickness to a postage stamp, thin-film strips are typically prepared using hydrophilic polymers for oral administration, with the user placing the strip on or under the tongue or along the inside of the cheek where saliva serves to rapidly dissolve the dosage form. 

This drug delivery option also allows the medication to bypass the first pass metabolism, thereby giving the medication significantly more bioavailability than conventional tablet dosage forms. Films alleviate the danger/fear of choking, are easy to handle and administer, have a pleasant mouthfeel and taste and are straightforward to manufacture. They offer the combined advantages of ease and convenience of dosing in the absence of water, anytime, anywhere.

An ideal film should exhibit adequate flexibility, elasticity and softness, resistance to breakage, taste compliance and minimum disintegration time. All these parameters need to be evaluated during the formulation development stage and required standard protocols. The greatest challenge is to develop a high quality film, which also necessitates constant evaluation and understanding of the performance of the dosage form, the critical steps to achieve successful product development. Despite the intense focus on film-based drug delivery systems, there are no official standardised methods for their evaluation. 

Polymeric films are also finding a wider range of applications in pharmaceutical research and dosage form design, including tablet coatings and transdermal patches. The application of a particular polymeric formulation depends upon the physical and chemical properties of that material, including its mechanical, electrical, thermal and bonding properties. The mechanical properties of a material may be assessed by many methods, including tensile, shear, and compression techniques.  

Tensile characterisation is a rapid, widely used method for determining the properties of solid materials. Subjecting a solid material to a tensile stress allows the properties of the polymer in the solid state to be defined. Selection of types and amounts of different polymeric materials significantly alter the tensile properties of a material. For example, plasticisers are commonly added to brittle polymeric films in order to improve their flexibility and strength whilst offering reduced toxicity and shortened processing times. 

However, the film formation process is fundamentally different and the coalescence of the polymer particles is a critical step. To avoid incomplete film formation and instability during storage, the type and amount of added plasticiser, as well as the curing conditions, must be carefully selected and the effects on drug release kinetics and physical properties need to be assessed.

Measuring Film Properties

Miniature Tensile Grips for the
assessment of film tensile strength

Tensile Grips

Tensile Grips allow the investigation of the effect of varying formulation parameters, particularly drug loading and plasticiser content, on the tensile properties of candidate films and thus upon the clinical performance of the final drug delivery device. 

Tensile Grips, such as the Miniature Tensile Grips shown here, are attached to the base plate and loadcell carrier of the Texture Analyser. Typically the upper grip is adjusted  in order to leave a gap of exposed test material above the lower. Where the gap is set to 5mm, the tensile strength of films can then be measured according to ASTM Method D882-91. 

Results graph from tensile test
of pharmaceutical film

Strips of film (70mm x 10mm) are cut from the dried film with a scalpel. The samples are placed between, and perpendicular to, the tensile grips, which are tightened to ensure that the film does not slip out during the test. A tensile test is then performed at a speed of 0.5mm/s.

Tensile test results are calculated from load-extension curves and expressed as Tensile Strength, Work of Failure, Elastic Modulus and Extension (or Elongation) to Break. 

Tensile Strength = Load at Failure/Film Thickness x Film Width
Work of Failure = Area under Curve x Cross-head Speed/Film Thickness x Film Width
Elastic Modulus = Slope/Film Thickness x Film Width x Cross-head Speed

Methods that are not according to an ASTM Standard are also viable, where sample dimensions cannot be prepared according to the Standard and where the operator may wish to modify test parameters, such as the test speed. 

The operator should ensure that the length of the films exposed to the applied stress are constant. 

Ultimate Tensile Strength (or Break Strength as it may also be referred to), Elongation at Break and Young’s Modulus are typically calculated from such tensile tests, ensuring that the change of test parameters is reported.

One such example of empirical tensile testing is a traditional method taking a strip of gelatin film (such as that used for capsule manufacture), making a dumbbell-shaped piece for testing, placing the wide ends in the upper and lower jaws of a Texture Analyser and measuring the forces to stretch the film to a given distance and/or to rupture the film. Low speeds of 1 to 2mm/s are frequently used for gelatin film.

It should be noted that several variations of Tensile Grips are available, depending upon sample size, material strength and grip face requirements.

Pneumatic Grips

Testing a typical film sample
using Pneumatic Grips
attached to a TA.HDplus
Texture Analyser

 
Tensile strength can also be measured using Pneumatic Grips and a test procedure based on the ASTM D822-75d Method. 

Extension speed is 5mm/min. The load (kg) and the displacement (mm) at film rupture refer to the cross section and starting length of the film specimens and are converted to the nominal tensile strength (MPa) at rupture and the nominal elongation (%) at rupture.

Pneumatic Grips are often a preferred means of holding a sample for tensile testing, because the gripping pressure can be controlled precisely and because deformation of the specimen does not produce any change in the gripping pressure. This type of grip clamps the specimen by lever arms that are actuated by compressed air cylinders built into the grip bodies. A constant force maintained on the specimen compensates for decreases in force resulting from creep of the specimen in the grip. 

Another advantage of this design is the ability to optimise gripping force by adjusting the air pressure, making it possible to minimise specimen breaks at the grip faces.

Film Support Rig

The Film Support Rig with
spherical probe

Whilst Tensile Grips or Pneumatic Grips are the traditional choice for tensile testing, there are alternatives. 

A Film Support Rig is designed to hold small amounts of film in a drum configuration, in order to measure the mechanical properties of the films by using a puncture test. 

A 5mm diameter spherical probe is driven downwards to the centre of the film holder’s hole. The special raised internal lip increases the tension, eliminating the risk of operator error or variability. 

Comparison of burst strength of
two types of gel film

 During a test, the maximum force to rupture the product is typically recorded and is referred to as Burst Strength. The additional measurement of resilience, stiffness and relaxation of a wide range of products broadens the application of this rig.

For a more fundamental approach when using the Film Support Rig, load versus displacement curves such as those shown in the graph above [E] are recorded until rupture of the film and used to determine the % Elongation at Break, as follows:

Elongation at Break (%) =
√(R2 + d2) – R x 100%
R

where R denotes the radius of the film exposed in the cylindrical hole of the holder and D the displacement to puncture.

In addition, the Load vs Displacement curve (up to the rupture of the film) can determine the Energy at Break:

Energy at Break = AUC/V

where AUC is the Area Under the Load vs. Displacement Curve and V is the Volume of the film located in the die cavity of the film holder (the Energy at Break is normalised to the film’s volume).

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...

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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.

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.

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