T U R B I S C A N. Automatic stability analyses for pharmaceutics

Transcription

1 Automatic stability analyses for pharmaceutics

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

3 Stability of pharmaceutics Need for an accurate and objective technique to measure stability Turbiscan technology

4 Multiple Light Scattering BS=k(1/l*) Backscattering With k (dh) : dh = detector height l * =k (d/φ) Transport length of the photon With : d = particle mean diameter φ = volume fraction

5 Multiple Light Scattering - Effect of the volume fraction- Flux (%) ESTAPOR latex suspension (polystyrene in water) d = 0.3µm, np = 1.59, nf = 1.33, Wavelenght = 880nm T(%) BS(%) Model Model 0,0001 0,001 0,01 0, DILUTED REGIME Volume fraction (%) CONCENTRATED REGIME

6 Multiple Light Scattering - Effect of the particle size - BS (%) Latex suspensions from ESTAPOR (polystyrene in water) φ = 1%, np = 1.59, nf = 1.33, Wavelength= 880nm Experiment Model 0,01 0, Diameter (µm)

7 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

8 Backscattering (%) Principle of measurement One scan Height (mm) Multi scans Height (mm) Acquisition time of each profile

9 Principle of measurement Particle migration Sedimentation or creaming t=0 min t=15 min Particle size variation Coalescence or flocculation t=0 min t=15 min

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

11 Parenteral emulsions Stability profile of TPN emulsion 80% 70% 60% 50% 40% 30% 20% 10% CLARIFICATION CREAMING 0mm 20mm 40mm 60mm Fig.2 : Typical backscattering versus sample height and time for the clarification and the creaming of TPN mixtures. Experiment duration : 12 days, température : 37 C. j 1j 2j 5j 5j 7j 8j 8j 12j Effect of temperature on clarification 3 2,5 2 1,5 1 0,5 TPN 1 TPN 2 TPN 3 TPN 4 TPN 5 TPN 6 TPN Temperature ( C) Fig.3 : Linear relationship between the kinetic of clarification of TPN mixture and the temperature of storage. 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

12 Parenteral emulsions -Effect of antibiotic on injectable emulsions- Without antibiotic With 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) Effect of an additive on the stability of injectable emulsions

13 Ophthalmic suspensions o Mainly used as anti-inflammatory agents (corticosteroids) o Main destabilisations sedimentation flocculation o Need to be homogeneously redispersible

14 Ophthalmic suspensions -Sedimentation of dexamethasone suspension- 0.1% dexamethasone 0.1% dexamethasone % benzalkonium chloride 0.1% dexamethasone % polysorbate 80 Shape of sedimentation profiles informs on the aggregation behaviour B. Klinke, R. Süverkrüp «Sedimentation characterisation of dexamethasone ophthalmic suspensions by near infrared turbidimetry»

15 Pressurized Metered Dose Inhaler o Application: Asthma treatment o Working principle 10-40µm 5 µm o Requirements for high and constant quality Same dose each time (25-150µL) Same amount of active per dose Evaporation of the propellant Drug particles into lungs

16 Pressurized Metered Dose Inhaler o Turbiscan analysis : Sample in crimped cell Measurement in fixed position at the bottom and the top to follow fast destabilisation o Comparison with Timed Medication Delivery (TMD): measurement of the delivered dose

17 N. Govind, S. Liljedahl, Assessment of pressurized metered dose inhaler suspension formulations using the Turbiscan, Respiratory Drug Delivery VIII, 2002 Pressurized Metered Dose Inhaler Delta BS (%) 0,5 0,4 0,3 0,2 0,1 0 -Formulation 1 creaming Time (s) Creaming of the drug insufficient dose after 30s Measured dose (%) Bottom TMD

18 Pressurized Metered Dose Inhaler -Formulation 2 sedimentation- Delta BS (%) 0,75 0,6 0,45 0,3 0, Time (s) Sedimentation of the drug too much dose after 30s Measured dose (%) Bottom TMD N. Govind, S. Liljedahl, Assessment of pressurized metered dose inhaler suspension formulations using the Turbiscan, Respiratory Drug Delivery VIII, 2002

19 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

20 Conclusion The Turbiscan technology is: o Easy to use o Reliable o Time saving o Objective So you have more time and information to focus on formulation