International Journal of Pharmaceutics (v.512, #2)

Foreword: Special issue—geriatric drug therapy by Mine Orlu Gul; Fang Liu; Carmel Hughes (331).

Display OmittedThe substantial reduction in premature death and longevity is an achievement of modern societies and advances in technology, medical and pharmaceutical sciences. Derived from the effective management of acute and chronic diseases throughout the lifetime the typical age related, later life stage diseases will become more dominant characteristics in future patients as well as other age related impairments or life conditions. Naturally, this leads to patients with complex clinical and functional patterns that are accompanied by the necessity of therapeutic interventions and polypharmacy. With the increasing number of older people and especially those with very high age in the society, new distinct older patient populations are evolving that require patient centered therapies and drug products to maintain safety and efficacy as well as effectiveness. Understanding how the patient populations and their characteristics change from a clinical, daily functioning and a patient perspective is crucial to move towards patient centric drug products.
Keywords: Older patients; Patient centric; Multimorbidity; Therapeutic complexity; Polypharmacy;

Regulatory incentives to ensure better medicines for older people: From ICH E7 to the EMA reflection paper on quality aspects by Diana A. van Riet-Nales; Nasir Hussain; Katarina A.E. Sundberg; Doris Eggenschwyler; Cristina Ferris; Jean-Louis Robert; Francesca Cerreta (343-351).
Display OmittedAgeing comes with an increased propensity in the alteration of human organ and body functions, which can e.g. result in multi-morbidity, frailty, polypharmacy, altered medication safety and/or efficacy, and problems with the practical use of medicines in a real world setting. Such problems may e.g. involve difficulties opening containers, swallowing large tablets, breaking tablets by hand, or correctly understanding the user instruction. This review aims to summarize the European regulatory activities towards better medicines for older people, with a main focus on formulation development and the overall drug product design. It addresses the ICH E7 guideline “Studies in support of special populations, geriatrics”, the ICH Q8 guideline “Pharmaceutical development”, the EMA good practice guide on “Risk minimisation and prevention of medication errors” and the forthcoming EMA CHMP QWP reflection paper on the “Quality aspects (pharmaceutical development) of medicines for older people”. In addition, three key aspects to the practical use of medicines by older people are discussed in a wider context: multi-particulates including small tablets (also referred to as mini-tablets), ease of opening and storage conditions. Furthermore, attention is paid to work in progress e.g. incentives by the European national drug regulatory authorities, and patient centric drug product development.
Keywords: Aged [MesH]; Chemistry, pharmaceutical [MesH]; Drug approval [MesH]; Drug product design; EMA; Formulation; Guideline; Medication management; Mini-tablet; Reflection Paper; Older people;

An industrial perspective on the design and development of medicines for older patients by Sharon Page; Alastair Coupe; Andrew Barrett (352-354).
An increasing elderly population is leading to a change in the global demographics. This presents a new challenge to society and the pharmaceutical industry. This demographic shift is providing an opportunity for the pharmaceutical industry to meet the specific needs of the changing patient population. One issue that has been identified is defining what is meant by “an older patient”, since this definition cannot be simply limited to chronological age. The fundamental purpose of the design and development process is to create a product that can be used by the patient group in a safe and efficacious manner. In the pharmaceutical industry ICH Q8 is used to guide the design and development of medicines. The process leads to the definition of the Quality Target Product Profile (QTPP) for a specific drug product and patient population. One can imagine a product with various presentations described in the QTPP which suit paediatrics, adults and older patients. It is recognised that designing medicines for smaller population groups will result in multiple presentations that could lead to smaller manufacturing batch sizes. In the short to medium term; dose flexibility, easy-to-swallow formulations, and easier access packaging are all factors under consideration. Dose flexibility could be achieved with various dosage forms such as oral liquids, mini-tablets, or multi-particulates. Whilst patient dosage preferences are beginning to be understood, further investigation is needed to balance the needs of the patient, care giver, prescriber, and payer. There also remain a number of challenges with the engineering solutions and delivery device for mini-tablets and multi-particulates (aside from filled capsules) to accurately and robustly deliver the dose, and issues with handling the device and the packaging for an older patient. It is also recognised that there are numerous challenges, not least of which is the definition of the older patient and a generic QTPP for an older patients’ drug product. It is likely that there will be no simple solution or ‘one-size-fits-all’ approach in drug product development to resolve the complex issues presented by the ageing population.
Keywords: Older adults; Demographic; Pharmaceutical industry; Patient centric; ICH Q8; Quality target product profile; Solid oral formulation; Dosage form; Dose flexibility; Product handling; Product adherence; Smart packaging;

Patient centric formulations for paediatrics and geriatrics: Similarities and differences by Sara M. Hanning; Felipe L. Lopez; Ian C.K. Wong; Terry B. Ernest; Catherine Tuleu; Mine Orlu Gul (355-359).
Display OmittedPaediatrics and geriatrics both represent highly heterogenous populations and require special consideration when developing appropriate dosage forms. This paper discusses similarities, differences and considerations with respect to the development of appropriate medicine formulations for paediatrics and geriatrics. Arguably the most significant compliance challenge in older people is polypharmacy, whereas for children the largest barrier is taste. Pharmaceutical technology has progressed rapidly and technologies including FDCs, multi-particulates and orodispersible dosage forms provide unprecedented opportunities to develop novel and appropriate formulations for both old and new drugs. However, it is important for the formulation scientists to work closely with patients, carers and clinicians to develop such formulations for both the paediatric and geriatric population.
Keywords: Paediatric; Geriatric; Medicine; Excipients; Dosage form; Patient-centric;

Pharmaceutical strategies towards optimising polypharmacy in older people by Carmel M. Hughes; Cathal A. Cadogan; Deborah Patton; Cristín A. Ryan (360-365).
This paper focuses on the issue of polypharmacy in older people and potential pharmaceutical strategies to optimize the use of multiple medicines. Although polypharmacy has long been viewed negatively, increasing emphasis is being placed on the difference between appropriate and inappropriate polypharmacy. This is largely being driven by the increasing prevalence of multimorbidity and the use of evidence-based guidelines. In this paper, we outline a number of key considerations that are pertinent to optimizing polypharmacy, notably prescribing appropriate polypharmacy, pharmaceutical formulations, the involvement of older people in clinical trials and patient adherence.
Keywords: Polypharmacy; Prescribing; Formulation; Older people; Clinical trials; Adherence;

Novel methods of drug administration for the treatment and care of older patients by Helen L. Quinn; Carmel M. Hughes; Ryan F. Donnelly (366-373).
Display OmittedThe number of older people globally is increasing, contributing to a growing burden of morbidity and mortality. With this shift in population demographic, comes a new challenge in terms of appropriate healthcare for the over 65 years age group. As medication is the principal therapeutic intervention, it is essential that it be fully optimised, to meet the needs of this heterogeneous population. The most common routes of drug administration are oral and injectable, which may display some limitations for older people, in cases of dysphagia or frailty for example. This review considers alternative methods of drug delivery to the norm, specifically discussing the nasal, pulmonary and transdermal routes, as well as novel orally disintegrating tablets. The changing physiology as ageing occurs must be considered in the development of novel drug delivery devices. This review considers the various aspects of ageing that will influence future drug formulation design and development.
Keywords: Drug delivery; Ageing; Older people; Nasal route; Pulmonary route; Transdermal;

Percentage of participants selecting the tablet size and shape that started to cause difficulty in swallowing.Display OmittedOlder patients (aged 65 years and over) are the major consumers of medicines and many barriers affect their ability in taking medicines orally, especially swallowing difficulties. Moreover, the characteristics of differing medicine formulations might have an impact on their acceptability in older patients. The aims of this study were to validate a Medicines Acceptability Questionnaire (MAQ) and to assess acceptability of oral solid medicines in older ambulatory patients with and without dysphagia. One hundred and fifty six older patients attending community pharmacies were recruited and attended face to face interviews. Two questionnaires were administered during the interviews, the validated Sydney Swallow Questionnaire (SSQ) assessing oral and pharyngeal swallowing function and the newly developed MAQ evaluating patient acceptability of oral solid medicines. Seventeen (11%) participants displayed symptoms compatible with swallowing difficulties identified by the SSQ. Participants with swallowing difficulties were considered themselves more likely to have problems in swallowing tablets and capsules of large sizes (11 mm and 13 mm tablets and size #00 capsules) compared to participants without dysphagia. Dispersible/effervescent tablets and orally disintegrating tablets were considered to be the most acceptable in this cohort, followed by mini-tablets. Chewable tablets and granules were the least favoured. Consistently higher acceptability scores were seen in the dysphagic population than in the non-dysphagic population for all of the dosage forms that were easier to swallow than tablets and capsules. The development of these formulations will assist in medication taking in older patients with dysphagia and potentially their adherence to drug treatments.
Keywords: Geriatric; Elderly; Swallow; Medication; Acceptance; Preference;

Age-mediated changes in the gastrointestinal tract by Hamid A. Merchant; Fang Liu; Mine Orlu Gul; Abdul W. Basit (382-395).
Display OmittedPhysiological functions of the two extreme ends of the age spectrum, children (<18 y old) and older adults (aged 65 y and over), differ from healthy young adults. This consequently affects the pharmacokinetic profiles of administered drugs, which, in turn, impacts upon clinical practice and drug therapy. The gastrointestinal milieu acts as a distinct and vital organ regulating the dissolution, absorption and metabolism of orally ingested drugs. Age-mediated alteration in the physiology and function of the gut can reshape the pharmacokinetics of certain drugs. However, our understanding of this topic is limited. This article references the gut physiology of healthy adults to capture the available evidence in the literature on the extent and nature of the changes in childhood and older age. The gut, as an organ, is examined with regards to the effect of age on luminal fluid, microbiota, transit and motility, and the intestinal mucosa. Whilst drastic developmental changes were observed in certain aspects of the gastrointestinal environment, the examination reveals significant gaps in our knowledge in the physiology and function of the developing or ageing gut. The revelation of the unknown paves the way towards a better characterization of the human gastrointestinal tract for optimized drug therapy in children and older adults.
Keywords: Personalised medicine; Paediatrics; Geriatrics; Aging; Bioavailability; Gastrointestinal tract;

Challenges to optimal medicines use in people living with dementia and their caregivers: A literature review by Dalal Alsaeed; Elizabeth Jamieson; Mine Orlu Gul; Felicity J. Smith (396-404).
Display OmittedDementia is fast becoming a global concern due to a demographic shift towards an older population. Many studies have shown that caring for a family member or friend has a profound and negative impact on the physical, emotional and psychosocial aspects of the caregivers’ life. One significant activity that a family caregiver undertakes is assistance with the management of medicines. This review was undertaken to ascertain what the issues are that affect optimal medicines use from the perspectives of people living with dementia and their caregivers, both in the community and care home settings. A literature search was conducted using electronic databases, employing a combination of search terms. A total of 16 studies met the inclusion criteria. Six broad themes were identified, together with some recommendations to improve medicines use in people with dementia. Challenges to medicines use centred on medicines management and administration, the impact on the caregiver and care recipient, their partnership and interface with formal care. Future research should focus on developing targeted interventions that can overcome these challenges to achieve optimal medicines use.
Keywords: Dementia; Medicines use; Medication administration; Medication management; Challenge; Family caregiver/carer;

Display OmittedThe aim of this paper was to explore how aging influences the nail unit, its disorders and its response to treatment, and to identify some of the age-related gaps in the ungual drug delivery literature. Aging causes obvious changes to the nail, some of which are inherently due to old age, while others are due to diseases/conditions which become more prevalent as we age. Alterations in the nail plate’s colour, contour, thickness, fragility, surface features, cell size, chemical composition and growth rate are some of the changes, with toenails and fingernails showing different effects. With respect to disease, the incidence of onychomycosis – the most common nail disorder – is considerably higher in older people. Similarly, brittle nails become more common as we age. In contrast, the literature about aging and the incidence of nail psoriasis is inconclusive, although, it is clear that as one gets older, the negative impact of nail psoriasis on one’s quality of life decreases. Pharmaceutical treatment of the diseases comprises local and systemic therapies, sometimes in combination. Systemic therapies have the inherent disadvantages of adverse systemic effects, drug interactions and the need for monitoring, disadvantages which are especially problematic for older people who are more likely to suffer from co-morbidities and be on other medications. Topical therapy avoids such disadvantages. However, the success rates of commercially available preparations are low, and older people may need help with their application. It is also proposed that regular inspection and grooming of nails should become part of routine care of older people, as these would provide opportunities to identify and treat any problems at an earlier stage.
Keywords: Nail; Onychomycosis; Psoriasis; Older; Elderly; Geriatric; disease; Ungual;

Display OmittedBlisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient’s compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient’s satisfaction, were investigated by target group testing according to ONR CEN/TS 15945.For each testing 20 participants in the age of 65–80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure.To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure.
Keywords: CEN/TS 15945; Blister packaging; Solid dosage forms; Easy opening; Dimension ratio tablet cavity; Seniors; Target group test;

Medicines administration for residents with dysphagia in care homes: A small scale observational study to improve practice by Jose Manuel Serrano Santos; Fiona Poland; David Wright; Timothy Longmore (416-421).
Display OmittedIn the UK, 69.5% of residents in care homes are exposed to one or more medication errors and 50% have some form of dysphagia. Hospital research identified that nurses frequently crush tablets to facilitate swallowing but this has not been explored in care homes. This project aimed to observe the administration of medicines to patients with dysphagia (PWD) and without in care homes.A convenient sample of general practitioners in North Yorkshire invited care homes with nursing, to participate in the study. A pharmacist specialised in dysphagia observed nurses during drug rounds and compared these practices with national guidelines. Deviations were classified as types of medication administration errors (MAEs).Overall, 738 administrations were observed from 166 patients of which 38 patients (22.9%) had dysphagia. MAE rates were 57.3% and 30.8% for PWD and those without respectively (p < 0.001). PWD were more likely to experience inappropriate prescribing (IP). Signs of aspiration were more frequently observed in PWD when IP occurred (p < 0.001).Observation of medication administration practices by independent pharmacists may enable the identification of potentially dangerous practices and be used as a method of staff support. Unidentified signs of aspiration suggest that nurses require training in dysphagia and need to communicate its presence to the resident’s GP. Further research should explore the design of an effective training for nurses.
Keywords: Medicines; Dysphagia; Swallowing difficulties; Prescribing; Medicines administration; Care home with nursing; Nursing home; Deglutition; Deglutition disorders;