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Re-imagining yourODT Formulation
Introducing a New Lactose Product
SuperTab® 50ODT
Mara van Haandel, MScInnovation Manager, DFE PharmaDDF Berlin, 12 March 2019
Spray-dried Granulated
Anhydrous
Moving from standard offerings to innovative solutions,
while maintaining the same focus on product consistency
DFE Pharma Direct Compression Portfolio: Evolution of lactose grades
•Standard offering
•Compactable, spherical morphology enhancing flowability
SuperTab® 11SD
•Enhanced compactabilityby reducing the primary particle size
SuperTab® 14SD •Rapid disintegration due
to microporous structure
•Enhanced mouthfeel
SuperTab® 50ODT
•Standard offering
•Highly compactable
SuperTab® 21AN
•Improved flowability by fines reduction
SuperTab® 22AN
•Agglomerated anhydrous
•Increased compactability and reduced disintegration time
SuperTab® 24AN
•Agglomerated anhydrous and lactitol
•Excellent flow, excellent compactibility, soluble
SuperTab® 40LL
•Great all-round product with good compactabilitycombined with good flowability and disintegration properties
SuperTab® 30GR
ODTs differ from traditional tablets in that they are designed to be dissolved on the tongue rather than swallowed as a whole. The regulatory condition to meet the ODT requirement:
- disintegrate in less than 30 seconds for US ODT products
- less than 3 minutes for European ODT products.
Main challenge of orally disintegrating tablet
ODT’s are a novel way for product line extensions and a new manner helping to deliver medication to pediatrics and geriatric patients, or to those who suffer from Dysphagia.
Challenges:• Tablet should dissolve fast• Tablet should have a pleasant mouthfeel• Tablet should have robust tablets (high hardness and low friability)
Good
Mouthfeel
FastDisintegration
Low
Friability
Pleasant mouthfeelMildly sweet -disaccharide
Robust tablet hardnessLow friability ensuring consistent performance
Fast dissolving speed Fast disintegration due to macropores by design
SuperTab® 50 ODT : Re-imagine your ODT formulation
New future possibilities
- ODT market is growing - Product Line extension - Increased comfort of taking medication- Proceed in pursuit of excipient excellence
Key users criteria
SuperTab® 50 ODT
Friability
Tablet tensile strenght
Source: Invivo Friesland Campina global sensory development Wageningen - CATA RATA method
Sensory is…
As perceived by the senses
The awareness through the senses
Sensory testing: using people as “measuring device”
The five senses
Interaction between product properties, sensory properties and consumer behavior
Sensory: product perception & measurement by ensuring quality and objectivity
7
We use people as a “measuring device”
Screening:
Only the best tasters are selected
- Basic taste test
- Ranking tests
- Odour & Flavour recognition test
Training:
Dedicated panelists are extensively trained on tablets
- Generate attributes
- Determine definitions
- Ranking & scaling of products on attributes
Monitoring:
Panelists are continuously monitored on:
- Reproducibility
- In line with each other
- Distinguish between products on all attributes
Procedure for tablet production and sensory evaluation
Tablet production:• Formulation: 95.5 wt% of filler, 4 wt% superdisintegrant, 0.5 wt% lubricant. • Blending process: Turbula blender 90 rpm 8+2 min.• Compression process: Tablets (250 mg, 9 mm flat bevelet) were produced at 50 N
tablet hardness
The 50ODT panel : • #14 trained people• Age: 20-60 years old • Randomly tested (single
blind)
Sensory evaluation: 1. Attribute generation & reduction (only keeping the
relevant attributes for the panel and the requester)2. Training the panel on the attributes; focusing on
definitions 3. Practicing the scale for the RATA attributes (Rate all
that apply)4. Practice test & check quality of results 5. Final (short) training session based on practice test
results6. Official CATA/RATA test for project
a. Taste one product and evaluate the attribute listb. Neutralize: cracker + waterc. Taste next product etc.
Test set-up
Testing method: a combination of CATA (Check All That Apply) and RATA(Rate All That Apply). The RATA method is used when possible for attributes that require more differentiation in the results.
RATA: CATA:
Taste and mouthfeel attributes
Attribute Taste/Mouthfeel Description CATA/RATA
Sweet Dextro Taste Grape sugar CATA: No | Yes
Chalky Taste Taste like chalk CATA: No | Yes
Sweet Taste Overall sweet taste RATA: Not | a little bit | a bit | average | very | extremely
Paper/cardboard/ mouldy Taste Paper taste RATA: Not | a little bit | a bit | average | very | extremely
Soft/creamy Mouthfeel Granules present during melting
CATA: No | Yes
Powdery Mouthfeel Sandy texture of tablet during melting
CATA: No | Yes
Dissolves into paste Mouthfeel Product dissolves at once instead of melting gradually
CATA: No | Yes
Melts immediately Mouthfeel Product starts melting/ dissolving immediately when in mouth
CATA: No | Yes
Crumbling at end Mouthfeel Tablet becomes granules at the end
CATA: No | Yes
Dissolving speed Mouthfeel The speed of dissolving Rata: Extremely fast | very fast | fast | normal | slow | very slow
Amount of effort needed Mouthfeel Effort to dissolve RATA: From little effort needed till a lot of effort needed
The outcome of Sensory testings
High dissolving
Very sweet
High dissolving speed; Directly starts to melt; Powdery; Dry; Paper
Directly starts to melt; Powdery; Dry
Very low in sweetness; Paper; Melts in phases; Crumbly; Powdery; Dry
Very low dissolving speed; Crumbly
Very sweet; Dextro sweet; Fruity; High dissolving speed; Dircetlystarts to melt; Dissolves into paste; Velvet
Very sweet; Dextrosweet; Directly starts to melt
Observations (axes F1 and F2: 61,39%)
F1 (37,98%)
F2
(23,
41%
)
CompA
CompB
CompC
CompD
SuperTab® 50ODT
Disintegration In-vivo vs In-vitro
Co-processed SuperTab® 50 ODT Mannitol
Dissolving speed
In-vitro: Measured in 800ml water Invivo: Measured Real environment
Co-processed
High
Medium
Low
SuperTab® 50 ODT supports faster disintegration due tomacropores by design
• SuperTab® 50 ODT shows a rapid disintegration resulting from spray drying.
• A 100% inert, stable, soluble and palatable excipient
• Lactose based ODT excipient allowing steering capability by adding a superdisintegrant finding the balance best fitting the formulation.
Co-processed SuperTab® 50 ODT Mannitol
Dissolving speed
Source: Invivo Friesland Campina global sensory development Wageningen
High
Medium
Low
0
10
20
30
40
50
60
70
80
90
100
1 10 100 1000
Cu
mu
lati
ve u
nd
ers
ize
(%
)
Particle size (um)
SuperTab 50 ODT
SuperTab® 50 ODT enhances mouthfeel due to macroporous by design
• SuperTab® 50 ODT was found to have a mildly sweet taste as it is a disaccharide excipient.
• Modification by spray drying offers porosity which enhances a good mouthfeel defined by its ease of use in the mouth and fast dissolving time
• Powdery/ grittiness is prevented due to primary particle size of less than 35 µm*
Not A little bit A bit Average Very ExtremelyEffort needed (Amount of effort needed to dissolve)
Dissolving speed (dissolves quickly)
Not A little bit A bit Average Very Extremely
Testing method : RATA –Rate All That Apply CATA –Check All That Apply
Immediately starts melting
Melts gradually
Powdery
Crumbly
Aimed: Performance of lactose as alternative excipient versus mannitol in ODT.
* E. Imai, 1995, Oral perception of grittiness: effect of particle size and concentration of the dispersed particles; Beckett, 2008, Industrial Chocolate Manufacture and use
SuperTab® 50 ODT enables robust tablet hardness at a given compaction force
Find the right balance between hardness and disintegration
Robust tablet hardness
Typically ODT’s are tableted soft (at a lowcompaction force). SuperTab® 50 ODT has a lowfriability (<0.5%w/w) ensuring consistentperformance on tablet hardness over time. Thiscombined with a good tensile strength at a givencompaction force.
Friability
Tablet tensile strenght
SuperTab® 50 ODT : A monohydrate lactose modified by spray drying
Microscopy (SEM):lactose monohydrate modified by spray drying
Parameter Spec
<45um(airjet sieve)
Max 20%
<106um(airjet sieve)
30-60%
<250um(airjet sieve)
>90%
0
10
20
30
40
50
60
70
80
90
100
1 10 100 1000
Cu
mu
lati
ve u
nd
ers
ize
(%
)
Particle size (um)
SuperTab 50 ODT
Parameter Typical
Bulk Density 0.64
Tapped density 0.73
HR 1.14
Car’s index 12%
FFC 22
x10 55
x50 130
x90 220
Main techniques used in preparation of orally disintegrating tablets (ODT) :• Freeze drying (lyophilization) • DC of spray dried /co-processed excipients
SuperTab® 50 ODT produced on our spray dryer in Borculo
Product Information
• A 100% lactose based ODT excipient to re-imagine ODT formulations
• Packed in 25kg boxes
• Re-test: 18 months
SuperTab® 50 ODT Reimagine your ODT
Good
Mouthfeel
FastDisintegration
Low
Friability
SuperTab® 50 ODT provides
• Pleasant mouthfeel by it’s ease of use, dissolving speed and disscharide
• 100% natural, inert and soluble• Robust tablet hardness, due to low friability • Unlike polyols, lactose does not decrease small intestinal
transit time*
Targetting:
Pediatric and geriatric patients
Key users criteria
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