Transcript Development of ARV FDC for Pediatric use

Development of ARV FDC for
Pediatric use
Alan Parr, Pharm.D., Ph.D.
GlaxoSmithKline
Research Triangle Park, NC
Presentation Outline
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Introduction
Physical/Chemical considerations
Formulation consideration
Packaging considerations
Conclusions
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 2
Introduction
• Development of formulations for pediatric
population is very challenging for the following
reasons:
– Requires a wide range of doses (not achievable using
solid dosage forms)
– Limited patient populations to evaluate efficacy of
compound/product
– Difficulty in doing studies in this patient population
– Potential biological differences (e.g., metabolic
differences) between pediatric patients and adult
patients
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 3
Overall Formulation considerations
for Pediatric Formulations
• Need to be aware of taste preference
which differ significantly around the world
• Need to be aware of sweetness
preferences which differ from around the
world
• Need to be aware of the limit of inactive
ingredients administered per the dosing
regimen
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 4
Physical/Chemical considerations
for Pediatric formulations
• Solubility of drug substance
• Stability of the drug substance in solution
• Compatibility of drug substance with
excipients (e.g., flavors, sweeteners,
preservatives)
• Stability of multiple drug substances in a
given formulation
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 5
Formulation consideration for
Pediatric formulations
(Chemical basis)
• Chemical stability of the drug substance
• Chemical stability of the preservative
system
• Chemical stability of flavor and sweetening
system
• Impact of the buffering system on drug
substance stability
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 6
Formulation consideration for
Pediatric formulations
(Physical basis)
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Loss of taste (e.g., sweetness and flavor)
pH of the product
Viscosity of the product
Change of color of the product
Mouth feel
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 7
Packaging considerations for
Pediatric formulations
• Compatibility of packaging components with:
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The drug substance
The preservatives
The flavors and sweeteners
The pH and buffering system
• Absorption or adsorption of drug and inactive
ingredients
• Amount and type of leachables
• Headspace in the container
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 8
Conclusions
• Development of a pediatric formulation is
very challenging and complex
• It requires a balance between a number of
different variables to ensure a consistent
product with appropriate stability,
preservative system, and acceptable taste
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 9
Back-up Slides
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 10
Available Formulations that could
be used in Pediatric Patients
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Abacavir (Ziagen®) Pediatric Oral Solution (GSK)
Didanosine (Videx®) Pediatric Powder (BMS)
Lamivudine (Epivir®) Oral Solution (GSK)
Stavudine (Zerit®) Oral Solution (BMS)
Zidovudine (Retrovir®) Syrup (GSK)
Nevirapine (Viramune®) Suspension (BI)
Amprenavir (Agenerase®) Pediatric Oral Solution (GSK)
Fosamprenavir (Lexiva®) Suspension* (GSK)
Lopinavir/Ritonavir (Kaletra®) Pediatric Oral Solution (Abbott)
Nelfinavir (Viracept®) Powder for Oral Suspension (Agouron/Pfizer)
Ritonavir (Norvir®) Oral Solution (Abbott)
* Under development
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 11
Formulation Options for
Pediatric patients
• Oral solutions
• Oral suspensions
• Sachets
– Note: need to re-constitute with a specific
volume of liquid to dose on a mg/kg or mg/m2
WHO Meeting
03NOV2004
E://presentations/WHO110304a
Slide 12