Whilst early development and ageing processes can affect the acceptability and appropriateness of different dosage forms for administration to either paediatric or geriatric populations, each patient should be considered on an individual basis. The fact that someone is young or old does not necessarily mean that they will experience the problems commonly associated with their ‘physical age’. It is however important for the designers of dosage forms to be aware of potential age-related problems and how these affect the suitability of different formulations depending on the ‘behavioural age’ or ‘developmental age’ of the patient. Furthermore, pharmacists and pharmaceutical scientists should be aware of the different options available to them, and be able to provide suitable products and advice on the most appropriate dosage form, formulation or method of administration.

Paediatric and geriatric populations

The paediatric population is generally classified into five age groups (ICH E11):

• Preterm newborn infants – those who are born before 38 weeks of pregnancy

• Term newborn infants – those who are less than one month old

• Infants and toddlers – those who are aged between one month and 2 years of age

• Children – those who are aged 2 to 11 years

• Adolescents – those who are 12 to 16–18 years (dependent on regional definitions).

The geriatric population is arbitrarily defined as comprising patients aged 65 years or older (ICH E7). Nevertheless, patients in the older age range of 75 years and over may need further consideration during the design and administration of medicines.

Swallowing oral dosage forms

Tablets and capsules are the most commonly prescribed solid dosage forms because they are relatively cheap to produce, are portable, can be coated to mask unpleasant flavours or formulated to modify the drug release profile. Furthermore, their dry nature provides a stable environment for the drug, and hence gives the final product a relatively long shelf-life. Whilst such medicines are popular with prescribers they are not always the most suitable for patients with swallowing difficulties that can result from either a psychological aversion to swallowing tablets or a physical impairment to swallowing (dysphagia). Psychological aversion to swallowing tablets, which usually originates in childhood, is prevalent in all age groups, whereas dysphagia is much more common in older people.

The swallowing process

The swallowing process comprises three phases: the oral, pharyngeal and oesophageal phases (Fig. 43.1). Within the oral phase (Fig. 43.1b) the bolus is manipulated by the tongue in preparation for swallowing, usually breaking larger objects into smaller ones and mixing with saliva to make the bolus both soft and less adhesive. During the pharyngeal phase (Fig. 43.1c) muscle control is sub-conscious and the bolus is moved into the pharynx where the passage to the lungs is automatically closed via movement of the epiglottis. Within the oesophageal phase (Fig. 43.1d) the bolus passes beyond the upper oesophageal sphincter and into the oesophagus. Although movement of the bolus is partially controlled by peristaltic waves within the oesophagus which occur automatically in response to swallowing, the movement of objects within the oesophagus is largely as a result of gravity. Consequently, tablets and capsules are most easily swallowed in an upright position (with the patient sitting or standing up) and this advice is commonly given to patients for tablets or capsules which are known to cause oesophageal irritation, e.g. doxycycline.

Fig. 43.1 Anatomy of the mouth and phases of bolus swallowing. (a) anatomy of the mouth, (b) oral phase, (c) pharyngeal phase, (d) oesophageal phase.

Paediatric populations

Swallowing problems are common in young children. Before 4 or 5 months of age, infants possess an extrusion reflex which enables them to swallow only liquids. Moreover, a gag reflex of varying degrees can last up until about seven to nine months of age. Hence eating requires active effort and the child must be able to coordinate sucking, swallowing and breathing. Infants are ready for spoon-feeding of semi-solids by 4 to 6 months of age. Although they are not capable at that age of swallowing a monolithic dosage form (e.g. a tablet), multiparticulates (powders, granules, pellets, minitablets <3 mm) might be given sprinkled into soft food (if compatible). At ages above about 6 years, children are considered able to swallow conventional tablets or capsules. Generally, the smaller the solid dosage form, the easier it is for children to swallow, but inter-individual differences in swallowing ability should be considered.

Geriatric populations

The loss of muscle control associated with the swallowing process is of concern for the administration of tablets and capsules to the elderly. As people get older, saliva production generally reduces and this can make it more difficult to swallow tablets or capsules, which require some lubrication before swallowing. This can however be easily overcome by taking the tablets or capsules with a glass of water; reduction in saliva should not in itself be a reason for patients not to be prescribed such solid dosage forms. Furthermore, tablets or capsules administered without water can be held in the pharynx or oesophagus and this can increase the likelihood of local erosion or irritation and therefore all patients, irrespective of age, should be told take tablets and capsules with water.

Loss of muscle control during the oral phase of swallowing can make it difficult to create a manageable bolus for swallowing, may cause the ‘loss’ of small tablets within the oral cavity or can make it more difficult psychologically to overcome the gag reflex that is necessary to swallow tablets or capsules. Loss of muscle control during the pharyngeal phase, which is controlled subconsciously, can increase the likelihood of choking, or at least the anticipation of choking, if it is not possible to propel the bolus through this phase. During the pharyngeal phase the airway is temporarily closed to allow the safe passage of food or liquids into the stomach, if solid dosage forms lodge in this area, the epiglottis will not open and the patient will asphyxiate.

Loss of control of the epiglottis during the pharyngeal phase can result in it not closing as the bolus passes and consequently the contents may inadvertently be aspirated into the lungs. The main defence mechanism within the lungs is the cough reflex, whereby contents are forcibly removed under pressure. A natural and background production of mucus which transports materials out of the lungs is another mechanism of removing foreign and waste products. However this has limited capacity and is restricted to small particles. Consequently, unintended aspiration of non-sterile foods or medicines can increase the likelihood of pulmonary infections, which are more likely to be fatal in an older person.

In addition to the ageing process, conditions commonly associated with ageing such as dementia, stroke, gastro-oesophageal reflex disease (GORD), Parkinson’s disease and cancer can all cause difficulties when orally administering tablets and capsules. The loss of muscle control associated with the progression of Parkinson’s disease and dementia results in dysphagia in the majority of patients with these diagnoses. It is estimated that almost 70% of people who suffer a stroke will have some form of dysphagia immediately post-stroke. However, in the majority of patients the normal swallow returns and less than 10% of people who experience a stroke are found to have permanent dysphagia. Dementia, stroke and Parkinson’s disease have greatest impact on the oral and pharyngeal phases of swallowing and therefore patients become concerned about choking and aspiration with these conditions. Head, neck and gastrointestinal cancers can all cause dysphagia by blocking access to the stomach, whilst radiotherapy and chemotherapy can affect the oral and gastrointestinal mucosa therefore making swallowing more difficult. Persistent GORD can cause inflammation within the oesophagus and this can result in patients describing foods and medicines ‘sticking in the back of their throats’ with a consequential struggle to swallow.

The nature of the dysphagia is therefore important when deciding the best approach for the patient. For patients who are struggling to manipulate oral doses, increasing the bulk of a medicine or the addition of water to the swallow may make it easier for the patient; whereas those who have dysphagia due to a blockage may require physically very small doses or low viscosity liquids. In those patients who are at risk of aspiration it may be inappropriate to administer tablets with water as the mixed consistencies may increase the likelihood of aspiration. Consequently, a single bolus of a thicker consistency may be more appropriate for such patients.

Assessment of swallowing ability

Speech and language therapists are usually the most appropriate professionals to assess the swallowing process. This may involve a brief bedside assessment via questioning and a test requiring the patient to drink a glass of watert. More invasive procedures include use of a naso-gastric camera (fibre optic endoscopic examination or FEES) or an X-ray of the swallow of a radio opaque liquid material (videofluoroscopy). The assessment should determine whether the oral route is appropriate and if so what the optimal texture of administered foods and medicines should be. This should provide some insight into the best pharmaceutical formulation for that patient.

If dysphagia is not identified in a patient and an inappropriate formulation is prescribed then this may affect the patient’s ability or willingness to self-administer perorally. Evidence suggests that older people frequently deny or ignore swallowing problems as this is indicative of ageing. An older person’s ability to swallow oral medicines should however always be ascertained by the prescriber to ensure that they are given the most appropriate formulation.

Helping patients with swallowing difficulties

Where patients with dysphagia are still able to use the oral route, the prescriber or pharmacist has three main options available to them:

• determine whether the medicine is still required or whether it can be safely discontinued

• identify a suitable formulation which can be swallowed

• identify an alternative route of administration.

In reviewing the on-going need for the medicine, the pharmacist, together with the prescriber, should determine if the medicine is effective and if so, whether the benefits of the therapy outweigh any risks during administration. Additionally, if the dysphagia is likely to be acute, as may be seen immediately following a stroke, then medicines may be temporarily stopped until the swallow mechanism reappears.

Formulation of paediatric and geriatric medicines

Liquid peroral dosage forms

Formulating liquid, rather than solid medicines provides some particular problems for the pharmaceutical industry due to the need to keep the drug stable in the usually aqueous environment, to ensure that the final mixture is palatable and to ensure dosing consistency. Selection of a suitable liquid vehicle and environmental conditions requires significant investment, as does the selection of appropriate antimicrobials, stabilizers, suspending agents and flavourings (see Chapter 24). The combination of complex formulation science, relatively short shelf-lives (compared to tablets and capsules) and the relatively small market size, results in a lack of availability of licensed liquid medicines for many drugs. Moreover, liquid formulations often cost significantly more than their solid dosage form counterparts. Where licensed liquid medicines are available the texture may not always be appropriate and therefore this also requires consideration.

Paediatric considerations

In children, liquids are actually easy to administer and offer flexible yet accurate dosing with an appropriate dosing device. The most suitable of these are oral syringes, graduated in mL, which can cater for the heterogeneous paediatric population and for a single child as it grows. However, the taste or smell of the drug can sometimes be difficult to mask in a liquid formulation and this is a strong deterrent to patient compliance.

Selection of appropriate excipients

Formulation of liquids usually requires many excipients. These excipients can present a significant toxicological risk to a patient, depending on numerous factors including: the age of the child and their clinical condition, the route of administration, the exposure (dose and dosing frequency) and the safety profile of the excipient (allergies and sensitization, acute and cumulative toxicity) as illustrated in Table 43.1. The formulator of a liquid medicine needs to make rational choices of added excipients; deciding on their purpose and, if their use is inappropriate, an alternative must be sought. A striking example is the case of elixirs; these liquid formulations generally contain an appreciable percentage of ethanol and have historically been used (and some still are) in neonates and infants. The inclusion of ethanol in paediatric medicines should be avoided, especially for babies and vulnerable patients who are not able to metabolize it as efficiently as adults.

Table 43.1

Excipients with elevated toxicological risk for the subpopulations of paediatric and geriatric patients

(Data from Breitkreutz and Tuleu 2009.)

Sweeteners and flavouring agents.

These are used to mask the taste of liquids and tablets, such as chewable and dispersible tablets. A sweet flavour can be achieved by the use of sweeteners that may be categorized as follows: