Implications of crushing paracetamol tablets prior
to administration in yoghurt to elderly patients:
Is there a dilemma?
S. Carson, E. Pardoe, S. Robertson and B. Glass
School of Pharmacy and Molecular Sciences,
James Cook University, Townsville, QLD.
1
Introduction
• What is the dilemma?
– Aged population
– Medication load in the elderly
– Increase in swallowing difficulties
• Dysphagia
• CVA
• Parkinson’s Disease
• Dementia
• Decreased Consciousness
– Majority of medications are tablets or capsules
– Most oral medications are crushed
– Trans-dermal products, rectal administration
Medication Safety for Older People, Adelaide, March 2011 2
Introduction
• Crushing of medication
– enables easier administration to the elderly with dysphagia
– enables ‘covert’ administration
– is necessary as limited availability of liquid formulations
Medication Safety for Older People, Adelaide, March 2011 3
Introduction
• Lipitor ® (Atorvastatin)
– Size of a cashew nut or
more than 2cm
• Caltrate® (Calcium Carbonate)
• Fish Oil
Medication Safety for Older People, Adelaide, March 2011 4
Introduction
WHY NO ORAL LIQUIDS?
• Limited market size – but need is increasing
• Stability of liquid formulations
• Often paediatric formulations
– Expense
– Paracetamol 1000mg qid = 20ml qid (48mg/ml)
• Available liquid preparations:
– Digoxin
– Frusemide
– Haloperidol
– Risperidone
– Some Opioids
Medication Safety for Older People, Adelaide, March 2011 5
Objective
• To determine whether crushing paracetamol tablets and mixing
the powder in a vehicle (yoghurt) had implications on:
– Stability
– Dissolution profile
– Bioavailability
of this simple analgesic
Medication Safety for Older People, Adelaide, March 2011 6
Why paracetamol in vanilla yogurt?
• Registered nurses in aged Medication being Number of
crushed patients
care facility in Townsville
were surveyed: Coloxyl and Senna 20
– Vehicle for administering tablets
crushed medications.
• Chocolate syrup Paracetamol 500mg 19
• Jam tablets
• Custard
Aspirin 100mg tablets 10
• Mashed banana
• Audit of medication charts
for crushed medications Frusemide 40mg 7
tables
Medication Safety for Older People, Adelaide, March 2011 7
Unlicensed Use
• Crushing / opening capsule alters the dosage form
resulting in:
– Unlicensed use of medication
– Manufacturer is released of liability
• Liability moves to
– Person crushing / administering medicines
– Doctor (if ordering medicine to be crushed)
• Pharmacist can give advice on altering dosage form
– Expert on dosage forms – design and excipients
Medication Safety for Older People, Adelaide, March 2011 8
Altering a dosage form
• Potential to cause a primary loss of dose:
– By the process of crushing, transferring and administration
– Important in medications with low therapeutic index
• Warfarin
• Potential for secondary loss of dose by:
– Altered absorption
– Stability changes
– Local (gastrointestinal) irritation
– Altered taste/texture
– Change to intended site of action
Medication Safety for Older People, Adelaide, March 2011 9
Paracetamol - Stability
METHOD
• Pure paracetamol powder mixed with yoghurt
• Mixture dissolved in methanol
• Solution diluted and filtered
• Concentration of paracetamol measured by UV
spectrophotometry
RESULT
• Yoghurt demonstrated not to interfere with analysis
• Analytical method validation
• Specificity
• Measured paracetamol concentration agreed with amount
added method of analysis valid
Medication Safety for Older People, Adelaide, March 2011 10
Paracetamol - Stability
METHOD
• Paracetamol (Panamax®) 500mg tablet crushed in a
mortar and pestle
• Crushed drug (plus excipients) mixed with vanilla yoghurt and let
stand for time periods up to 60 minutes
• Mixture dissolved in methanol and analysed by UV
spectrophotometry as previous testing.
RESULT
No significant difference observed in paracetamol levels
measured immediately after mixing and those allowed to stand
for 60 minutes
Stability of paracetamol + excipients (Panamax®) in yoghurt is
acceptable
Medication Safety for Older People, Adelaide, March 2011 11
Method - Dissolution
• Paracetamol (Panamax®) 500mg tablet crushed in a mortar and
pestle
• Crushed drug (plus excipients) mixed with different quantities
of vanilla yoghurt and spread across a watch glass
• The paste was spread to increase surface area
• The watch glass was placed in a dissolution apparatus
Medication Safety for Older People, Adelaide, March 2011 12
Method - Dissolution
• USP has guidelines for dissolution of paracetamol
- Minimum of 80% of the drug must be dissolved following 30
minutes at 50rpm in 900ml of pH 5.8 phosphate buffer
• Vankel VK 7000 Dissolution Testing Station
- Simulated motion of stomach with rotating paddle
- Containing phosphate buffer
- pH 5.8 (USP)
- 50 rpm (USP)
Medication Safety for Older People, Adelaide, March 2011 13
Method- Dissolution
Figure 1. Photograph of Dissolution Apparatus - Vankel VK7000
Method - Dissolution
• Comparative dissolution studies were conducted to
determine the difference in dissolution between:
– one whole tablet
– one whole crushed tablet
– one whole crushed tablet mixed with varying amounts of
yoghurt
• At timed intervals, samples removed, filtered, diluted and analysed
by UV spectrophotometry
• All studies performed in triplicate
Medication Safety for Older People, Adelaide, March 2011 15
Results- Dissolution
Paracetamol Dissolution Profiles
100
80
% drug dissolution
60
40
Crushed tablet
Whole tablet
20
Crushed tablet +
spoon yoghurt
0
0 5 10 15 20 25 30 35
Time /min
Figure 2. Dissolution profiles of crushed , whole tablet and crushed tablet in yogurt 16
Discussion
• Disintegration precedes dissolution
• Difference in the crushed and whole tablet reflects the
step of manual disintegration by crushing the tablet
(Figure 2)
– Results comply with the USP Standard
• Dissolution is altered by addition of yoghurt
• Medium retards dissolution
– Does not comply with USP Standard (80% / 30 min)
• Less than 40% of drug dissolved after 30 minutes
Medication Safety for Older People, Adelaide, March 2011 17
Results- Dissolution
100
80
%Drug Dissolution
60
40
20 1.0 g yoghurt
2.0 g yoghurt
3.6 g yoghurt
0
0 5 10 15 20 25 30
Time /min
Figure 3. Dissolution profiles of crushed tablet mixed with various amounts of yogurt 18
Results- Dissolution
Figure 4. Crushed Panamax tablet + 1.0 g of yogurt
Medication Safety for Older People, Adelaide, March 2011 19
Summary
• Is it is acceptable to crush paracetamol and
administer it in yoghurt ?
– Yes as stability is not adversely affected
• Is there an effect on the dissolution profile of
paracetamol once it is crushed and mixed with
yoghurt?
– Yes
• Does the amount of yoghurt used affect dissolution?
– Yes
Medication Safety for Older People, Adelaide, March 2011 20
Is the dilemma solved?
• NO!
Amount of vehicle (yoghurt )used in the practice =
3.6g or more.
– The amount of vehicle (yoghurt) necessary to
• Comply with the USP Standard for dissolution is
1.0 g
– 1.0 g yoghurt + 1 tablet is a thick paste
• Not palatable
• Not easy to swallow
21
Medication Safety for Older People, Adelaide, March 2011
Solving the dilemma
• The process of testing the extracted drug
validated.
• Scope to test other vehicles / amounts
– Custard
– Jam
– Chocolate syrup
– Designer formulation
• Scope to test other medications
– Thyroxine
– Warfarin
– Frusemide
Medication Safety for Older People, Adelaide, March 2011 22
References
• Pardoe E. 2010. „Stability Effects of Crushing Paracetamol tablets: A
model protocol‟ B. Pharm. Hons. James Cook University, Townsville.
• Haywood A, Glass B. 2007. “Managing Extemperaneous Oral Liquids
in Practice” Journal of Pharmacy Practice and Research, Vol .37, no.
2, pp. 131-3.
• Stubbs J, Haw C, Dickens G 2008, „Dose form modifications – a
common but potentially hazardous practice. A literature review and
study of medicaiton administration to older psychiatric inpatients‟ ,
International Psychogeriatrics, Vol 20, no 3, pp.616-27
• Paradiso L, Roughead E, Gilbert A, Cost D, Nation L, Barnes L etal
2002, „Crushing or altering medications: what‟s happening in
residential aged-care facilities? Australasian Journal on Aging’ vol 21
no3. 2002 pp, 123-27
Medication Safety for Older People, Adelaide, March 2011 23
Thank you
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