Performance Evaluation of Actimask 92S
Ibuprofen: A Novel Taste-Masked Ibuprofen for
Use in Orally-Dispersible Dosage Forms
Author: Brian D. Wilson
Background
Objective
Recently, orally-dispersible dosage forms, including orally-dispersible tablets (ODT)
and orally-dispersible powders (ODP) have become increasingly more popular. The
numerous benefits of orally-dispersible systems include convenience, improved
compliance, increased bioavailability, and is easily dosed to pediatric, geriatric, and
debilitated patients.
To evaluate the physical characteristics,
dissolution characteristics, and
in-formulation characteristics of a
novel, taste-masked ibuprofen.
Results
A major hurdle in developing orally-dispersible dosage forms is the taste profile of
API’s. Amines and carboxylic acids are common API functional groups, which exhibit
sour and bitter taste perceptions, respectively. For this reason it is necessary to
develop taste-masked API’s to avoid an unpleasant taste from the active ingredient
during the ODT or ODP residing time in the mouth.
An ideal taste-masking system should leave no residue, provide a great mouth feel,
and resist fracturing during direct compression. The Actimask® 92S Ibuprofen’s
hydrophilic coating readily wets resulting in pleasing organoleptics. In addition, the
coating is shown to be durable in compression up to 30kN in tablets made with SPI
Pharma’s Pharmaburst 500 ODT system.
The Actimask® taste-masking technology from SPI Pharma provides a barrier to the
initial taste of the product, while still exceeding the compendial target of release in 60
min. The smooth hydrophilic coating technology yields a uniform product with a tight
particle size distribution, great flow, and a high assay value of 92%. Another significant
advantage of the Actimask system is that it is devoid of residual solvents as the entire
taste-masking process is aqueous.
Methods
Physical Characteristics: Bulk density, tapped density, and angle of repose were
evaluated on a Hosokawa Powder Tester. The PSD of the multi-particulate was
determined on a Microtrac particle size analyzer.
Dissolution Characteristics: The dissolution profiles of the raw material and
formulated material were determined with a Varian dissolution tester (900ml USP pH
7.2, Apparatus 2; 50rpm, Temperature 37°C (±0.5°C).
Sampling: (1, 5, 15, 30, 60 min) Ibuprofen was assayed by reverse phase
chromatography.
Formulated Tablets: Orally disintegrating tablets (ODT) containing 108.7mg tastemasked ibuprofen (equivalent to 100mg IBU) and 217.38mg taste-masked ibuprofen
(equivalent to 200mg IBU) were manufactured. Tablet physical characteristics and
ibuprofen dissolution profiles were determined for each of these tablets.
Bulk density, tapped density, angle of
repose, and PSD were determined.
Actimask® 92S Ibuprofen release in
USP pH 7.2 phosphate buffer was as
follows: 1min=7.6%, 5min=25.0%,
15min=54.4%, 30min=79.3%, and
60min=97.0%.
100mg and 200mg ibuprofen
containing ODT’s met USP immediate
release dissolution requirements.
Manufactured ODTs met USP
dissolution requirement (NLT 80%
ibuprofen release in 60 minutes) and
significantly slowed ibuprofen release
at the 1-minute time point compared
with ibuprofen IR Tablets per f2
analysis.
Conclusion
Actimask® 92S Ibuprofen was easily incorporated into 100 and 200mg ODT formulations. In manufactured ODT’s, the Actimask delays
early-phase release (taste masking) as compared to IR IBU tablets demonstrating taste-barrier characteristics, but meets USP 60min
dissolution requirements for IR release of ibuprofen.
Actimask® 92S Ibuprofen is an aqueous based, hydrophilic, uniformly coated taste-masked Ibuprophen.
Durable orally disintegrating tablets can be manufactured from various concentrations of Actimask® 92S Ibuprofen and Pharmaburst
500 ODT system by adjusting compression force in accordance to dilution with active.
Ibuprophen ODT’s manufactured with Actimask® 92S Ibuprofen and Pharmaburst 500 at various compression forces exhibited USP/
EP disintegration times of under 30 seconds over the majority of design space.
For all manufactured ODT’s, the release at 1 min (taste-masking period) was significantly less than IR formulations, demonstrating the
efficiency of taste-masking provided by Actimask® 92S Ibuprofen in the formulated systems. Conversely, at 15 minutes, active release
was complete, demonstrating the ability of Actimask® 92S Ibuprofen to meet USP requirements of Ibuprophen release for IR tablets.
Thus, Actimask® IBU provides for both taste-masking and speed to efficacy.
Figures 1 and 2: Actimask® 92S Ibuprofen
Figures 3 and 4: Actimask® 92S Ibuprofen (SEM’s)
Uniform
Hydrophilic
Coating of Active
ODT Formulas - Dissolutions
++321z
Figure 5: 100 mg IBU ODT Formula
1.00%
1.50% 1.00% .40%
15.50%
2.50%
3.00%
3.00%
Composition
% (By Weight)
mg / Tablet
Actimask IBU 92S
15.50
108.70
Pharmaburst 500
72.10
504.50
Crospovidone XL
3.00
21.00
Grape Flavor
3.00
21.00
SSF
2.50
17.50
Tartaric acid
1.50
2.80
Sucralose
1.00
7.00
Silicon Dioxide
1.00
7.00
Colorcon purple
0.40
10.50
Final Tablet Weight
700.00
72.10%
Manufacturing
1. Weigh and screen each ingredient through a #20 mesh (Co-screen color with lubricant).
2. Blend all non-lubricant ingredients in a PK blender (25rpm) for 15 minutes.
3. Add color and lubricant co-screen to blend 2 and blend 5 minutes.
4. Compress 700mg tablets on a GP-8 tablet press outfitted with 0.5” x 0.5” Arc Square - Reduced Cup Depth “D” punches at
25rpm and 600N pre-compression. Compress to a tablet hardness of 5 – 7 kP.
100mg IBU ODT
TW (mg)
T (mm)
H (kp)
Fr (%)
USP/EP DT (sec)
700
6.6
5.3
0.173
13
++215z
Figure 6: 200 mg IBU ODT Formula
1.00%
1.00%
5.00%
.08%
.03%
18.12%
Composition
2.5%
1.25%
2.00%
% (By Weight) mg / Tablet
Actimask IBU 92S
18.12
217.39
Pharmaburst
69.03
828.41
Natural Orange Flavor
2.00
24.00
Sucralose
1.25
15.00
SSF
2.50
30.00
Crospovidone XL
5.00
60.00
Silicon Dioxide
1.00
12.00
Critic Acid
1.00
12.00
FD&C Yellow #5
0.08
0.90
FD&C Red #40
0.03
0.30
Final Tablet Weight
69.03%
1200.00
Manufacturing
1. Weigh and screen each ingredient through a #20 mesh (Co-screen color with lubricant).
2. Blend all non-lubricant ingredients in a PK (25rpm) blender for 15 minutes.
3. Add lubricant and color co-screen to blend 2 and blend 5 minutes.
4.Compress 1200mg tablets on a GP-8 tablet press outfitted with 0.57” x 0.57” Arc Square “D” punches at 25 rpm and 1 kN of precompression. Compress to a tablet hardness of 6 – 8 kP.
200mg IBU ODT
TW (mg)
T (mm)
H (kp)
Fr (%)
USP/EP DT (sec)
1200
9.1
6.5
0.235
18
100%
Compression Force (kN)
80%
60%
40%
100mg TM IBU
200mg TM IBU
20%
Ibuprophen powder
0%
0
10
20
30
Time (min)
40
50
60
100%
Compression Force (kN)
80%
60%
40%
100mg TM IBU
200mg TM IBU
20%
Ibuprophen powder
0%
0
10
20
30
40
50
60
Time (min)
rpm Media: 900ml 0.1 N HCl Temperature: 37 °C
10%
Compression Force (kN)
8%
6%
4%
100mg TM IBU
200mg TM IBU
2%
Ibuprophen powder
0%
0
10
20
30
40
50
60
Time (min)
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