As the pharmaceutical industry embraces new delivery mechanisms to improve efficacy and patient compliance, the author discusses how to develop novel oral dosage drugs that are robust during processing and throughout transport and storage, yet easy to use, safe and effective for the patient.
Oral drug delivery is one of the most convenient, and most common, methods of delivering medication. Its simplicity and cost-effectiveness have made it particularly popular with manufacturers in the pharmaceutical industry, but it is not always the most popular with consumers.
Traditionally, orally-administered drugs are dispensed in a solid form, such as capsules or tablets, and liquid forms, such as solution or emulsion. Tablets are widely accepted due to their ease of manufacture and convenience in terms of self-administration and compactness, yet a large number of people have difficulty swallowing solid tablets. Children, the elderly and people with certain illnesses or disabilities may not take their medications as prescribed due to swallowing problems. To overcome these difficulties, patients may crush, break or chew their tablets, which can lead to changes in drug absorption or variation in dosage sizes.
As the pharmaceutical industry continues to grow and diversify, NPD and quality control departments have never been busier – or more challenged. In today’s tough environment, multiple complex regulatory requirements have to be juggled with innovative ingredients, new packaging formats, changing consumer demand and financial pressures. Never before has it been so difficult to perfect a product and achieve long-term commercial success.
Consumers have come to expect a personalised experience in many aspects of their lives, and the way they take their medication is no exception. The wealth of information available has allowed them to become more educated than ever before, and this knowledge is being used to request specific products and treatments in their personal therapy. Patients that have difficulty swallowing, as well as those caring for people who are struggling, expect to be able to receive their medication in a way that is convenient to them.
With pharmaceutical products needing to appeal to a wider range of preferences, manufacturers need to develop new, patient-friendly dosage forms. Effervescent tablets, lozenges, films and chewable tablets are examples of dosages forms that are not only more appealing, but also tackle the challenges faced by the consumers who struggle to swallow solid tablets.
Sensation in the mouth, taste and ease of intake are the main factors that influence a patient’s experience when taking medication.
When developing new dosage forms, the large amount of research necessary may be intimidating to manufacturers. New products need to maintain the same high quality and safety standards while also delivering a format that is appealing to a wider range of patients. This means that stringent testing must take place to perfect a product and achieve long-term commercial success.
The analysis of textural (or rheological) properties is an assessment or measurement of a particular characteristic, such as adhesiveness, hardness, break strength or elasticity. Contrary to verbal description (sticky, tacky, gooey, gummy), texture analysis made these rheological characteristics quantifiable – and therefore comparable.
One alternative method to deliver medication is Orally Disintegrating Tablets (ODTs), also known as fast melting or fast dissolving tablets. ODTs are designed to rapidly dissolve in the mouth, in less than three minutes, before swallowing. No other source of liquid is required for ODTs, making them a popular option for patients with dysphagia or children too young to swallow. The key properties of ODTs are fast absorption of water into the core of the tablets and disintegration of associated particles into individual components for fast dissolution. In addition, they must be strong enough to endure manufacturing and shipping yet friable enough to deliver an optimum dissolution rate. To ensure that the tablets meet all requirements, thorough testing
is required. Equipment is available that facilitates the assessment of these properties. Rigs can replicate the in vivo conditions of a human mouth, with the
dry tablet sample secured to a probe with a ‘channelled’ design that allows fluid to flow freely around the tablet. The test shows the water absorption and disintegration of the tablet, allowing manufacturers to record its disintegration time and behaviour and giving a valuable insight into performance and efficacy.
Thin-film drug delivery is another delivery method that has emerged as an alternative to the traditional tablet. In addition to being convenient to administer and easier to swallow, films also allow the medication to bypass the first pass delivery, which gives the medication more bioavailability than conventional tablets. Ideally, films should exhibit flexibility, elasticity and softness, whilst also being resistant to breakage and taste compliant with minimum disintegration time.
There is a number of testing methods available to evaluate a film’s performance. Tensile characterisation involves subjecting the film to tensile stress, allowing the properties of the film in its solid state to be defined. The use of Tensile Grips or Pneumatic Grips can provide details on the force require to
stretch the film to a given distance and/or breaking point.
Lozenges are a popular option for administering medication to children. Using sugar and solidified gum, they are consumed by light chewing that allows them to dissolve in the mouth. Lozenges are most commonly used to medicate the throat and mouth or for the slow administration of vitamins, with flavour options and textures that appeal to the age group and making it easier to integrate them into a daily routine. Lozenges are made by pouring a thick liquid mixture into a powdered, sugared or waxed mould. The liquid mixture is commonly based on starch and gum arabic, emulsifying with added oils and extracts and binding them. The combination of starch and gum arabic also reduces the dissolution rate and moderates the delivery of active substances, while the gum arabic also hardens the pastilles for easier storage and transportation.
Firmness and stickiness are the two most important properties of lozenges, with hardness providing an insight into the effects of different formulations and stickiness showing useful measurements, such as the potential of tooth pulling. In the majority of cases, a simple penetration test is suitable to evaluate the firmness of the gel. Stickiness can also be easily measured by lowering a small, cylinder probe down to the product’s surface and recording the force needed to withdraw it upwards.
Orally Disintegrating Granules (ODG) are currently used for pain relief and allergies in adults, but singular paediatric 4mg granules are suitable for children aged six months to five years. Granules can either be administered directly or mixed with a spoonful of soft food, such as apple sauce or ice-cream, increasing their popularity as a method of easy administration. Granule compressibility testing provides crucial measurement of physical strength and breakdown characteristics. The testing of single granules is discouraged as repeatability is compromised. Testing a fixed area of sample instead creates an averaging effect over a larger number of granules, improving the quality of results. One well-known instrument provides a circular testing area contains the sample before a compression with a cylinder probe. The maximum force and energy are then recorded and used as an indication of the compressibility of the granules.
Oral sprays deliver drug-containing aqueous droplets to the mouth. It is currently a suitable drug delivery method for sufferers of angina, insomnia and multiple sclerosis, and an alternative to injectable insulin formulations for those with diabetes.
Self-administration creates an even greater need for the safe and accurate delivery of any drug. Metering valve systems can be affected by alterations to design and product performance is dependent on the interaction between the elastomeric components and the drug formulation.
Texture analysis instruments can imitate the downward movement of the finger, measuring the force needed to actuate the spray and administer the dose. A rig which mimics the movement of the finger onto the inhaler, can measure the force needed to administer the dose.
In a highly competitive market, pharmaceutical manufacturers need to be able to deliver high-quality, customised products to meet their customers’ needs. Providing oral dosages of medication in forms other than in traditional targets makes products more accessible to a large number of people. By working with the right partners, providing novel oral dosages forms does not need to come at the cost of quality.