Fang Liu University of Hertfordshire

Transcription

1 Fang Liu University of Hertfordshire

2 Increasing attention from industry and academia in developing formulations for children since 2007 Raising recognition of the need of older patients There are similarities and differences in developing formulations for children and elderly What can the old learn from the young?; here we draw an emphasis on geriatric formulations

3 POSITIVE Converting NEGTIVE INTERNAL Strengths Weaknesses Matching EXTERNAL Opportunities Threats Converting No point of listing without an action plan!

4 Proceeding EMA Guideline on Pharmaceutical Development of Medicines for Paediatric Use Increasing availability of formulations designed for children Development of new formulations mini-tablets, multiparticulates, fast-dissolving films Understanding the suitability of excipients used for children Development of taste-testing and taste-masking techniques

5 Less attention and research in the area, however; Older patients could potentially benefit from the available medicines for children Research into new formulations for children could also be adapted for the elderly

6 Physiological differences from normal adults Physiological functions of the body Children development Ageing Swallowing difficulties

7 Children - taste and compliance (only an issue for the young?) Elderly - subdivision of age groups - disease states, comobidity, polypharmacy

8 Big change in 2007: EU legislation on medicines for paediatric use came into force, which increases: - the number of formulations suitable for children developed by industry - knowledge on critical aspects on developing paediatric formulations: dosage form suitability, palatability, excipients, manipulation

9 The world is ageing: - Proportion of over 65s in Europe rose from 8.8% to 15.9% between 1960 and 2005 and is estimated to rise to 29.9% by 2050 Society: increasing recognition in ageing and older people European Year of active ageing and solidarity between generation Regulation: EMA roadmap 2015 and Geriatric Medicines Strategy published in 2011 improving focus on needs of geriatric patients Pharmaceutical industry: adaptation in response to the ageing population in future development portfolio - treatment for age-related diseases e.g. Alzheimer's disease

10 Small market: - limits the investment in innovative and sophisticated formulations - simple dosage forms such as liquids are still dominant

11 In need of regulation similar to paediatrics - Less driving force for industrial investment - Knowledge and development lag behind paediatrics

12 Paediatrics - more and better medicines for children on the market fuelled by research in physiological changes in children, excipients, tast-testing/masking and new formulations Geriatrics - legislative movement in geriatric medication - guideline on pharmaceutical development of medicines for geriatric use

13 Physiological changes during ageing: affecting formulation design and performances - e.g. gastrointestinal physiology in elderly: ph, transit time, fluid volume, colon bacteria Taste concerns and preferences in elderly Excipients used for old patients

14 Disease states/comobidity affecting older people s swallowing ability and medication management - Drug administration in hospital wards/care homes/communities: identify potential risks: drug interaction/stability/bioavailability identify specific drugs/formulations with particular problems - Patient/carer perspectives We need to know where the problems lie!

15 A combined and bigger market: developing innovative and complex formulations which are commercially viable for example, modified release formulations - better efficacy/safety profile - more convenient to patients

16 Regulation requirement and incentive to pharmaceutical industry to consider geriatric patients in their medicinal product development Regulatory, industrial and academic experts to get together and discuss guideline for pharmaceutical development of medicines for elderly Understanding the physiological changes during ageing and their relevance to formulation design and in vivo performance More knowledge required for palatability issues in older patients and how this affect their medication adherence

17 Excipient considerations when used in older patients - does toxicity of excipients needs to be tested in the elderly? To start with, a database can be drawn from literature reports on such toxicity issues Conducting clinical investigations on the reality of drug administration/management by older patients and/or their care givers Developing more sophisticated formulations which could benefit both the old and the young and to be commercially viable

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19 Swallowing difficulties in the elderly A pilot study questionnaires to nursing homes (majority caring for elderly) in Herts & Beds (response 19.4%, n=37) - Semi-structured interview of 12 nursing staff % of patient identified by nursing home who: Have a Swallowing Difficulty Spit Out Medication Suck or Chew Medication Mean Median Std. Deviation Minimum Maximum Missing Responses Hide Medication

20 Methods to overcome swallowing difficulties 100 Percentage of homes (%) Tablet Capsule Omitting the Changing to Using an Hiding the crushing opening dose a liquid injectable dose in food formulation formulation and drink for oral delivery

21 Areas causing swallowing difficulties 27% 33% Size of tablet/capsule Shape of tablet/capsule 20% 20% Modified release preparations Liquid formulations

22 Tailored drug delivery: Modified release Microencapsulation: aqueous based formulations Enteric coating Controlled release Taste masking

23 Enteric coated microparticles using fluidised bed coating Particle size: 110 µm Eudragit L 30 D-55 aqueous coating 20 No particle agglomeration, yield: 5 90% 0 Percentage Drug Release (%) Acid stage Time (min) Buffer stage Percentage weigh gain 30% 40%

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