Automatic stability analyses for pharmaceutics

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Automatic stability analyses for pharmaceutics
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Stability of pharmaceutics

• Pharmaceutical formulations
• suspension (eye drops, drug powder, )
• emulsion (cream, lotion, parenteral emulsion, )
• aerosol (pMDI, sprays, )
• Stability is a critical issue
• particle size (risk of embolism, )
• sediment packing (drug dose, ease of
  redispersion)
• creaming (drug dose, emulsion breaking)

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Stability of pharmaceutics
Need for an accurate and objective technique to
measure stability
Turbiscan technology
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Multiple Light Scattering

BSk(1/l)
lk(d/f)
Backscattering
Transport length of the photon
With k (dh) dh detector height
With d particle mean diameter f volume
fraction
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Multiple Light Scattering
- Effect of the volume fraction-
DILUTED REGIME
CONCENTRATED REGIME
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Multiple Light Scattering
- Effect of the particle size -
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Principle of measurement
Acquisition of the - Transmitted flux
(T) and - Backscattered flux (BS)
Analysis of diluted to concentrated products
1 Acquisition every 40 µm
High vertical resolution
One scan lasts 20 seconds
Measurement of fast destabilisations
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Principle of measurement
One scan
Multi scans
Acquisition time of each profile
Backscattering ()
Height (mm)
Height (mm)
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Principle of measurement
Particle size variation
Particle migration
Coalescence or flocculation
Sedimentation or creaming
t0 min
t0 min
t15 min
t15 min
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Parenteral emulsions

• Total Parenteral Nutrition (TPN) emulsions
• lipid (base emulsion)
• glucose
• amino-acids
• vitamins
• Formulated in hospital and tailored upon patient
  health requirements
• Need to be highly stable for time of delivery

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Parenteral emulsions
Stability profile of TPN emulsion
Effect of temperature on clarification
? Creaming is exponentially dependent on
temperature and time of storage
V. Baradel, H. Constant, F. Falson, F. Pirot
Study of Parenteral Emulsion Stability using the
Optical Analyzer Turbiscan, Pharmaceutical
Science Fair 2005
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Parenteral emulsions
-Effect of antibiotic on injectable emulsions-
Without antibiotic
The antibiotic (amphotericin) has a small effect
on the emulsion C, and a more important one on
the emulsions from other suppliers (A, B and D)
With antibiotic

• ? Effect of an additive on the stability of
  injectable emulsions

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Ophthalmic suspensions

• Mainly used as anti-inflammatory agents
  (corticosteroids)
• Main destabilisations
• sedimentation
• flocculation
• Need to be homogeneously redispersible

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Ophthalmic suspensions
-Sedimentation of dexamethasone suspension-
0.1 dexamethasone
0.1 dexamethasone 0.01 benzalkonium chloride
? Shape of sedimentation profiles informs on the
aggregation behaviour
0.1 dexamethasone 0.01 polysorbate 80
B. Klinke, R. Süverkrüp  Sedimentation
characterisation of dexamethasone ophthalmic
suspensions by near infrared turbidimetry 
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Pressurized Metered Dose Inhaler

• Application Asthma treatment
• Working principle
• Requirements for high and constant quality
• Same dose each time (25-150µL)
• Same amount of active per dose

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Pressurized Metered Dose Inhaler

• Turbiscan analysis
• Sample in crimped cell
• Measurement in fixed position at the bottom and
  the top to follow fast destabilisation
• Comparison with Timed Medication Delivery (TMD)
  measurement of the delivered dose

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Pressurized Metered Dose Inhaler
-Formulation 1 creaming-

• Creaming of the drug insufficient dose
  after 30s

N. Govind, S. Liljedahl,Assessment of
pressurized metered dose inhaler suspension
formulations using the Turbiscan, Respiratory
Drug Delivery VIII, 2002
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Pressurized Metered Dose Inhaler
-Formulation 2 sedimentation-

• Sedimentation of the drug too much dose
  after 30s

N. Govind, S. Liljedahl,Assessment of
pressurized metered dose inhaler suspension
formulations using the Turbiscan, Respiratory
Drug Delivery VIII, 2002
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Long term stability analysis
-Automated analyses-

• Automatic handling with robot (80 runs per hour)
• Automatic data processing on whole group of
  samples
• Automatic sorting of samples with warning level
• Automatic reporting

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Conclusion
The Turbiscan technology is

• Easy to use
• Reliable
• Time saving
• Objective

• So you have more time and information to focus
  on formulation