Dr Mine ORLU GUL Lecturer in Pharmaceutics UCL School of Pharmacy m.gul@ucl.ac.uk

1. Coping with the management of medicine at old age: What older people think? What formulations scientists can do? Dr Mine ORLU GUL Lecturer in Pharmaceutics UCL School of Pharmacy m.gul@ucl.ac.uk

2. Patient centric drug delivery: A changing paradigm in healthcare • Key challenges and opportunities • What is patient centric ? • Development paradigm and the reality • Patient centric product design • Case studies • Conclusions

3. Patient Public Involvement

5. Demographic change • Elderly to constitute 20 % of India’s population by 2050 • By 2025, more than 20 % of the European population will be 65 years of age or older • By 2050, India and China will have about 80 % of the world's elderly living there • By 2050, 65 years or older Americans =88.5 million Need for investment in quality of health care Awareness is growing

6. Current Vision National EMA Workshop: `Ensuring safe and effective medicines for an ageing population` (March 2012) From EU: € 31 million to help address major concerns shared by all Europeans inc. coping with the challenge of an ageing population Major cross Research Councils UK initiative: Lifelong Health & Wellbeing World Health Day 2012: Ageing and health European UK Prime Minister visited the UCL Dementia Research Centre (March 2012) Dementia sufferers rise to a million by 2021 and 1.7 million by 2051 + rise in costs to £27bn by 2018 Dementia research funding will be doubled to £66 million by 2015 Global

7. Heterogeneity– there is no standard geriatric patient; ageing occurs at different rates “We are born as copies and die as originals” from Bo. G. Eriksson thesis on Studying ageing

8. Comorbidity • Defined as those with three or more diagnoses during the last 12 months, 19 days at hospital or three or more stays in hospital or more than seven visits to specialised physicians in outpatient care

9. Categorized as a • geriatric syndrome !! • Unfavourable adherence • Incalculable interactions • Accumulated ADR risk • Increased risk of hospitalization • Increased risk of medication errors • Increased costs Polypharmacy Threshold value to define critical polypharmacy: 5 or more POM + OTC risk

10. Polypharmacy • ED-North London 1 month data from ≥ 75 Banerjee et al. International Journal of Emergency Medicine 2011, 4:22 45% were on five or more POM

11. What is patient centric ?

12. Regulatory framework

15. Individualization of drug delivery strategyrequired = PATIENT-CENTRIC MEDICINE The product should be designed to meet patients’ needs From: ICH Q8 (R2)

16. Different Factors Affecting Acceptability of Medicines in Paediatric and Geriatric Patients Frailty & heterogeneity Immaturity Dispersing in liquids Adaptations to pill burden Aged/infirm care-giver Healthy care-giver Co-morbidity & Variation is more complex Variation is mainly due to body weight Palatability Dysphagia Senior friendly & simple Child-proof

17. Patient centric product design

18. Addressing motoric dysfunction • Ability to open pharmaceutical packaging in impacted by disease (Parkinson, stroke, dementia, RA)

19. Addressing visual decline • Visual impairments and poor vision are common in elderly. As the most important sensory organ this might impact the drug therapy • Polypharmacy is common among older adults increasing the challenge of product identification

20. Addressing cognitive capabilities • Health literacy • Set of skills needed to read, understand, locate and interpret healthcare information

21. Addressing cognitive capabilities

22. Addressing swallowing problems • Swallowing functions are declining with age and dysphagia are increasing with impact on • Oral medicines intake • Nutritional and hydration state • Morbidity and co-morbidity • Participation to social life

23. Drug delivery considerations as we age Decline in tear flow, tear volume; increase in tear evaporation rate Fluctuations in drug plasma conc. due to re-administration Weak tongue, poor control of muscles in the mouth Forced vital capacity reduction; decrease in inspiratory residual volume; thickened pulmonary arteries; thickening mucus layer; calcification of bronchial cartilage Increased gastric pH; increased gastric emptying time; decreased GI surface area Replenishment of SC declines; increased SC dryness; decrease in skin surface lipids; reduction in sebaceous gland activity; atrophy of skin capillary network

24. Strategies to overcome limitations From: Stegemann S. 2005 Pharm Ind

25. Multi-particulate formulations

26. Dual-release (sprinkle)

27. Fixed dose combinations

28. Research Themes in Geriatric Drug Delivery Group • Formulation of better medicine for older people • Tailored conventional formulations considering the effect of ageing on physiological and functional capacity • Advanced drug delivery systems designed for older people (micro- nano- particles / bubbles) • Improving off label medicine use in elderly including manipulations and extemporaneous dispensing • Developing palatable formulations and taste assessment

29. Ongoing research projects • Development of Amorphous Solid Dispersions of Melatonin for Pulmonary Delivery • DQAsomes for lung delivery of curcumin • Brief-access taste aversion (BATA) model (lickometer) for in vivo taste assessment) • Human Panels (‘swirl and spit’) for in vivo taste assessment • Production of dye-tagged ternary polymericmicroparticles with novel K-type microfluidic junction

30. Ongoing research projects • Study into Thin orodispersible film Acceptability as Medicine for Preschool children (STAMP) • Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CLOSED study) • Learning about carer errors and resilience strategies (CARE-ERRS): Equipment usability in using home enteral nutrition for older people • Investigation of the potential influence of thickening agents co-administered with medicine • Investigating the stability of repackaged medicine stored in multicompartment compliance aids • Development of fixed dose combinations using electrohydrodynamic approaches for the treatment of older people

31. APS Age Related Medicines Focus Group Main interest area Medicines for the older adult while being cognisant of and learning from the various paediatric initiatives Aims and objectives • Creating a platform that facilitates rapid translation of ideas to the older person`s and carer`s benefit • Involving pharmaceutical scientists / clinical researchers / representatives of the pharmaceutical industry committed to work in age-related medicines to prioritise and deliver the focus group`s research agenda • Providing strategic leadership and facilitating collaboration for joint research and grant applications • Developing links to associations / other age related networks / charities devoted to helping older people and carers http://www.apsgb.co.uk/focus_groups/

32. Interaction with scientific community Meetings / conferences • Interaction with regulatory bodies APS FG position statement on clinical and practical issues of geriatric drug delivery to the EMA Quality Working Party, as a contribution to the Reflection Paper that they will be drafting Submitted and acknowledged • Interaction with professional associations “Age-related medicines – Better outcomes for vulnerable patients” “Use of medicines in older people: the role of pharmaceutical sciences in the forgotten majority” “Pharmaceutical approaches into overcoming polypharmacy”

33. Geriatric Medicine Society A multidisciplinary network place to address the challenge of medicines for older patients from a holistic perspective Established in 2010 Registered non-for-profit organisation www.geriatric-medicine.org

34. Conclusions • Geriatric patient populations have their special drug delivery requirements with increasing importance considering current regulatory expectations and demographic trends of the older • Older patients deviate from the standard patient with regards to PK and PD, especially considering multimorbidity in old patients. These changes require dose adaptations and careful choice of excipients and dosage forms/application routes • Polypharmacy in geriatric patients represents a significant compliance challenge • New drug delivery systems and taste testing systems are now commercially available and developed trying to fulfill patient centric delivery requirements • Improvement of packaging aspects help to facilitate geriatric delivery • Patients will get more involved in therapeutic decision through their own perception of the disease and available therapies

35. Thank you.. Dr Mine ORLU GUL m.gul@ucl.ac.uk