Lipids for API microencapsulation

Effect of processing conditions on

product performance
Diogo G. Lopes
Index
1. Microparticles
i. Market demand
ii. Technologies
2. Advantages of Lipids as coating excipient
3. Physical behavior of lipids
i. Aging effect
ii. Lipid composition
iii. Polymorphism
iv. Microstructure
v. Blooming effect
4. Approaches to have stable products
5. Our approach


21.08.2014 RCPE Prsentationstitel 2
1. i. Market demand for microparticles
Improving product performance
Maximize drug absortion
Minimizing mucosa irritation
Reducing inter- and intrapatient variability

Increasing patient adherence
Improving swallowing
Size reduction
Taste and smell masking
Personalize doses
Nasogastric feeding

21.08.2014 RCPE Prsentationstitel 3
1. ii. Microencapsulation technologies
21.08.2014 RCPE Prsentationstitel 4
S. Gouin / Trends in Food Science & Technology 15 (2004) 330 - 347
Microcapsule
Microsphere /
Micromatrix
1. ii. Fluidized bed coating
Fluidized bed
Very efficient
Flexible
Either microcapsules or microspheres
Basically any kind of coating material
21.08.2014 RCPE Prsentationstitel 5
Schematic process of fluid bed microencapsulation Hot-melt fluid bed coater
2. Lipids as coating excipients
Functional properties
Improve stability by preventing the physical or chemical dregradation
Taste masking
Sustain drug release
Lubrification
Compressebility

Using GRAS excipients
Pediatrics
Predominant digestible

21.08.2014 RCPE Prsentationstitel 6
Lipid coating
Drug
2. Advantages of Lipids as coating
excipient
Industrial point of view
Toxicity and risk of explosion
Costly solvents and residue recovery step
Energy input
Microbial contamination risk

Advantages over polymers
Generally less amount
Relatively inexpensive
Drug release should not be influenced by the presence of alcohol


21.08.2014 RCPE Prsentationstitel 7
Organic solvents
Aqueous solvents
3. i. Aging effect
10% Cafene dispersion in Gelucire 50/13
Storage at 37 C
21.08.2014 RCPE Prsentationstitel 8
N. Khan; D. Craig / Journal of Pharmaceutical Sciences 93 (2004) 2962-71
Drug release profile DSC analysis
SEM images
3. Physical behavior of Lipid excipients
Lipid
Composition
Polymorphism
Microstructure
Macroscopic
properties
21.08.2014 RCPE Prsentationstitel 9
Processing
Conditions
3. ii. Lipid composition
Lipid
Composition
Polymorphism
Microstructure
Macroscopic
properties
21.08.2014 RCPE Prsentationstitel 10
Hydrogenated
vegetable oils
PEGs 200 -
2000
Saturated
Polyoxylglycerides
(Gelucires

)
Waxes
Fatty acids and partial glycerides
(Compritol

; Precirol

)
3. iii. Polymorphism of triglycerides
21.08.2014 RCPE Prsentationstitel 11
K. Sato / Chemical Engineering Science 56 (2001) 2255-2265
Lipid
Composition
Polymorphism
Microstructure
Macroscopic
properties
3. iv. Microstructure
Lipid
Composition
Polymorphism
Microstructure
Macroscopic
properties
21.08.2014 RCPE Prsentationstitel 12
A. Marangoni / Soft Matter 8 (2012) 1275-1300
3. v. Blooming effect
21.08.2014 RCPE Prsentationstitel 13
H. Mayama / Soft Matter 5 (2009) 856-859
4. Approaches to have stable products
Aging Step S. Salle / EP 1 479 383 A1 2004
Fluid bed at 10-15 C below the solidification point
Curing at 40C for 1 day

Tempering Step K. Chansanroj / J.Drug Del. Sci. Tech 17 2007
Fluid bed at solidification point
Curing at solidification point temperature for 3 hours

seeds approach Y. Kakiguchi / US 2003/0091648 A1
Fluid bed at no higher than solidification point
Adding -form seeds to the fluid bed
Curing for ten to several tens hours


21.08.2014 RCPE Prsentationstitel 14
4. Approaches to have
stable products
Tempering Step
Hydrogenated soybean oil (HSO)
Fluid bed at solidification point
Curing at solidification point temperature for 3 hours



21.08.2014 RCPE Prsentationstitel 15
N. Chansanroj / J. Drug Del. Sci. Tech 17 (2007) 347-352
5. i. Our Approach
Aim
Produce stable lipid coatings:
To have controlled drug release
Avoiding the aging step
Avoiding the bloomed surface
Produce microcapsules with:
Taste masking
Protection of the core drug from the environment


21.08.2014 RCPE Prsentationstitel 16
5. i. Theory
Theory

21.08.2014 RCPE Prsentationstitel 17
Lipid Composition
Polymorphism
Microstructure
Macroscopic properties