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Industry voice
Delayed release coating technology for nutritional supplements
Instanute DR is a new "pH dependent delay release ready
to use film coating system" for food supplements accepted in EU and US,
claim Dario Luini, Chetan Rajsharad and Suresh Pareek
Dario Luini
Area Manager, EMEA Ideal Cures, Europe Srl |
Chetan Rajsharad
VP – Technical
Ideal Cures |
Nutrition is a key aspect of health which often gets ignored.
People are too busy and preoccupied to pay attention to having a balanced diet.
This is where the nutraceutical and herbal industry plays a major role. However,
these industries face many challenges. One of the biggest challenge is to protect
and safeguard the nutritive value of their products. In case of solid oral dosage
forms, one consideration is the protection of certain active ingredients from
gastric degradation and masking unpleasant tastes and odours caused by their
release in the stomach. Usually a delayed release film is applied by film coating
process to postpone the release of active ingredients in the intestine.
The most used DR film coating systems in the EU and US markets
are based on the combination of Shellac (as sub- coating agent) and pre-gelatinised
starch (as top-coating agent). These are not based on pH dependent polymers/materials.
Therefore, the delay release mechanism is linked to the formation of a physical
barrier on the surface of the coated dosage form (insoluble in acid, neutral
and basic pH) which should protect it from the gastric environment.
The aim of this work is to characterise and evaluate the
performance of two food supplements approved as DR coating systems on nutritional
tablets.
Experimental methods
- Materials: Instanute DR and Shellac + pre-gelatinised
acetylated starch were selected as delayed release (DR) coating systems. Instanute
DR is a fully formulated pH dependent aqueous film coating system, based on
a natural polymer, designed specifically to meet the regulatory requirements
for food supplements, nutritional and herbal products in Europe and in the
US regions.
Both were characterised for mechanical properties (tensile
strength, elastic modulus, elongation strength) and coating performances on
multivitamine tablets.
Instanute DR has been dispersed at room temperature DI water (25°C) and
kept under soft stirring for 60 minutes prior to use (according to manufacturer's
guideline1).
The pre-gelatinised acetylated starch has been dispersed in hot water (90°C)
added with plasticiser (glycerol) and keep under stirring for two hours prior
to use (as per manufacturing guideline2). Dispersion quantities are listed in
Table 1.
| |
Instanute DR
|
Acetylated Starch
|
| Batch size (kg) |
3.5
|
3.5
|
| Weight gain (%) |
14
|
14
|
| Solid content (%) |
11
|
12
|
| DI water (25°C) (g) |
4005
|
|
| DI water (90°C) (g) |
|
3960
|
| Total dispersion (g) |
4500
|
4500
|
| Table 1: Dispersion composition |
- Tablet film coating: Multivitamin tablets were
coated in a conventional solid wall coating machine (Labcoat, Logica Progetti,
(Mi); 15 inches pan; equipped with 970 ABC gun, Schlick, D). The coating dispersion
was mixed continuously during coating. Process parameters are listed in Table
2.
- Film preparation: The dispersions were prepared
in hot stirred water (90°C) for the acetylated starch while the Instanute
DR was dispersed in cold and stirred water (25°C).
| |
Instanute DR
|
Acetylated Starch
|
| Batch size (kg) |
3.5
|
3.5
|
| Inlet Temperature (°C) |
60
|
80
|
| Exhaust Temperature (°C) |
40.2
|
50.2
|
| Product Temperature (°C) |
37.8
|
48
|
| Spray rate (g/min) |
15
|
10
|
| Atomising air pressure (bar) |
1.8
|
1.8
|
| Pattern air pressure (bar) |
1.8
|
1.8
|
| Air volume (m3/h) |
112
|
110
|
| Pan Speed (rpm) |
18
|
18
|
| Warm up time (min) |
10
|
10
|
| Total coating time (min) |
300
|
420
|
| Table 2: Film coating process
parameters |
Suresh Pareek
Managing Director,
Ideal Cures |
Free films were prepared by spraying the coating formulations
with a two-substance nozzle gun (Labcoat Nozzle Mod. 970 Form 7-1 S75 with Anti-Bearding-Cap,
nozzle tip bore 1.2 mm, Schlick) onto an horizontal roll (90 mm diameter, 150
mm length) covered with a silicone-coated paper rotating at 150 rpm. The atomising
air pressure was set at 0.8 bar and pattern pressure at 0.8 bar. A peristaltic
pump delivered the coating suspensions at 4.5 g/min (Evolution System, Logica
Progetti, I) and the suspension was kept under constant magnetic stirring. The
spraying nozzle was fixed at 220 mm from the roll and a hair-dryer was positioned
above the nebuliser with a 30° angle pointing towards the centre of the
spraying cone at 120 mm from the surface of the roll (air flux 10 m/s, temperature
100°C, Thermo-anemometer, Bergamo Collaudi, I). The temperature of the rotating
surface was checked with an IR-thermometer. During the film preparation the
temperature was 35-40°C.
The spraying procedure was interrupted after 10 minutes of
spraying (45 g of suspension sprayed). The films were removed from the silicone-coated
paper with the aid of a flat spatula and side areas were discarded.
Isolated films were stored in PE bags at room condition until
analysis.
Tensile testing was conducted using a texture analyser AG/MC1 (Acquati, I),
equipped with a 20N load cell. The film was cut into 30 x 20 mm strips and equilibrated
at 25°C for 48 hours. Tensile tests were performed according to ASTM International
Test Method for Thin Plastic Sheeting (D 882-02).
- Acid uptake: Acid uptake evaluations provide an
indication of the ability of the coating to protect the core from the effects
of gastric fluid3. Six tablets coated with Instanute DR and with acetylated
starch were individually weighed and fluid uptake was measured after exposure
to SGF for 60 minutes. After removing the samples from SGF and inspecting
for any defects (cracking, disintegrating, or softening), excess fluid was
removed with a towel and the samples were reweighed. The amount of SGF taken
up by both films was determined by calculating the per cent difference between
weights before and after exposure according to Equation.
- Disintegration testing: DT testing was performed
according to USP 32-NF 27 <2040>. Disintegration and dissolution of
dietary supplements, delayed release tablets (2010 revision)4. SGF and SIF
were prepared according to the USP.
Result and discussion
Instanute DR dispersion was easier to prepare as compared to acetylated starch.
This did not need any particular care in preparation (cold water and no plasticiser
to add). The reconstitution level of Instanute DR was lower due to high polymeric
concentration.
- Film properties: Mechanical properties of free
polymeric films were evaluated; the results are listed in Table 3. Instanute
DR films appeared to be more glossy and smooth; the acetylated starch films
were uniform although more rough. The tensile strength and elongation could
be considered not statistically different; looking at elastic modulus, acetylated
starch films appeared little more elastic.
| Film coating formulations |
Tensile strength (MPa)
|
Elastic Modulus (MPa)
|
Elongation strength (MPa)
|
| Instanute DR |
4.2
|
1.42
|
4.9
|
| Acetylated Starch |
4.5
|
1.16
|
5.4
|
| Table 3: Film properties |
Acid Uptake (per cent): x 100 Where:
Tf: Final tablet weight (mg)
Ti: Initial tablet weight (mg) |
Acid uptake: Acid uptake was evaluated on coated tablets
(n=6). Istanute DR coated tablets showed stronger acidic resistance due to the
real pH dependency nature of the polymer used; acetylated starch-coated tablet
showed 14 per cent, indicating a poor acidic resistance behaviour. Results are
showed in Figure 1.
Figure 1 Fluid uptake for free films |
Film coating process: Considering the total time of
the processes (reconstitution and film coating process) Instanute DR reached
the desiderate gastro-protection faster (see Table 4).
| |
Instanute DR
|
Acetylated Starch
|
| Reconstitution time (min) |
60
|
120
|
| Film coating process time (min) |
360
|
420
|
| Total process time (min) |
420
|
560
|
| Table 4: Process time |
Figure 2 Coated multivitaminc tablets |
Disintegration testing: Uncoated multivitamin tablets
eroded in 45 minutes in SGF. The coated tablets with both the coating formulae
met USP pharma and food supplements delayed release criteria: two hours in SGF.
The tablets coated with Instanute DR showed no evidence of disintegration, cracking
or softening; tablets coated with acetylated starch showed an hydrated surface
(Figure 3).
Figure 3 Coated tablets after two hour exposure to SGF |
When exposed to SIF, Instanute DR coated tablets showed a
complete dissolution of the film within 15 minutes (due to polymer pH dependency)
and complete erosion of the core in 60 minutes more; acetylated starch coated
tablets remained intact after two hours in SIF and took three hours to completely
erode.
Conclusions
Instanute DR is a new “pH dependent delay release ready to use film coating
system” for food supplements accepted in EU and US. The reconstitution
is easy, made in cold and stirred water as a common HPMC-based film coating
system; the delayed release performances satisfy USP requirements for delayed
release for pharmaand nutritional products.
References:
1-Ideal Cures, InstaNute DR Product Information Data Sheet
2-Cunningham C.R. et al. “One step aqueous enteric coating systems: scale
up evaluation” Pharm. Tech., 36-44, November 2001
3-USP 32-NF 27 <2040>
4-Young C.; Staffenino R.; Farrel T. “Performance comparison of two delayed
release coating systems for dietary supplements” presented at AAPSposter,
2010
About the authors: Dario Luini is Area Manager
EMEA Ideal Cures Europe Srl, Chetan Rajsharad is vice president – technical
and Suresh Pareek is managing director Ideal Cures. The authors can be reached
at: info@idealcures.co.in
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