Advantol™ 200 "Soft-Melt" for Nutraceutical Tablets
SPI Pharma’s Advantol platform uses proprietary co-processing technology. It can be used to develop a “soft-chew” or a “quick-melt” solid dosage form for nutraceutical applications. Advantol is a robust, off-the-shelf excipient system that allows the formulator to carry out product development work in their lab giving the nutraceutical company control of the development and testing activities. In addition, Advantol requires no special manufacturing equipment or tooling. Advantol formulations utilize a standard rotary tablet press with standard tooling under normal tableting temperature and humidity conditions to make robust “soft-melt” tablets. In contrast to using wet granulation or spray drying methods, SPI’s technology allows customers to simply add the active to Advantol, dry blend and compress, thus reducing the production cycle time and lowering costs. Table 1. Typical Properties of Advantol 200
| | Appearance | White granular free-flowing powder
| Loss on Drying
| NMT 2.6%
| Bulk Density
| 0.35-0.55 g/cc
| Tapped Density
| 0.53-0.73 g/cc | Angle of Repose
| 30-40° | | Angle of Fall | 21-27°
| Carr's Index
| 12.0 (28.0%) | Particle Size
| NMT 5 (% on) 30
NMT 45 (% Thru) 140
| Total Polyol Content
| 60-75%
|
Using Advantol 200 –Simply Dry Blend and Direct Compression
Formulations containing Advantol 200 are easily manufactured by direct compression process. The active(s) are blended with flavors, sweeteners, colors, etc. The mixture is blended with Advantol 200 for a specified mixing time. The lubricant is then added in the final step and blended for a minimum of 5 minutes. To demonstrate the simplicity of the formulations and versatility of Advantol 200, examples ranging in dose from very low 0.5 mg to as high as 500 mg were prepared. The formulations are provided in Tables 2-4. Figure 1. Particle Size Distribution of Advantol 200 Table 2. Advantol 200 Vitamin B12 with Folic Acid (47-034)
| | INGREDIENT | %
| mg/tablet
| | Advantol 200 | 94.67
| 246.14
| Vitamin B12
| 0.192
| 0.50
| | Folic Acid (10%) | 1.538
| 4.00
| Cherry Flavor
| 1.50
| 3.90
| Sucralose
| 0.50
| 1.30 | Red #40 (Al Lake 16%)
| 0.10
| 0.26
| Magnesium Stearate
| 1.50
| 3.90
| Total
| 100.00
| 260.00
|
| Table 3. Advantol 200 Vitamin C, 125 mg (47-036) | INGREDIENT
| %
| mg/tablet
| Advantol 200
| 79.03
| 592.75 | Ascorbic Acid
| 16.67
| 125.00
| Grape Flavor
| 2.00
| 15.00
| Sucralose
| 0.50
| 3.75
| Purple Lake Blend (LB-1898)
| 0.30
| 2.25
| Magnesium Stearate
| 1.50
| 11.25 | | Total | 100.00
| 750.00
|
| Table 4. Advantol 200 Glucosamine, 500 mg (47-026) | | INGREDIENT | %
| mg/tablet
| Advantol 200
| 63.91
| 1054.59
| Glucosamine (96.7%)
| 31.29
| 516.21
| Citric Acid
| 1.00
| 16.50
| Tutti-Frutti Flavor
| 0.50
| 24.75
| Sucralose
| 0.50
| 8.25
| | Yellow #6 (Al Lake 42%) | 0.30
| 4.95
| Magnesium Stearate
| 1.50
| 24.75
| Total
| 100.00
| 1650.0
|
Figure 2a. Oral Disintegration Times and Friability - Vitamin B12 + Folic Acid (Low dose) Tablet weight = 260 mg
Figure 2b. Oral Disintegration Times and Friability - Ascorbic Acid (Medium dose)
Tablet weight = 750 mg
Figure 2c. Oral Disintegration Times and Friability - Glucosamine (High dose) Tablet weight = 1650 mg Advantol 200 Produces Robust Tablets
Advantol allows robust tablets (low friability) to be manufactured while retaining its quick disintegration properties. Figures 2a-b show that Advantol tablets compressed at moderate tablet hardness will orally disintegrate in less than 60 seconds for small and medium sized tablets. Larger tablets, as shown in Figure 2c with Glucosamine, may take a little longer to disintegrate. For such large tablets one may wish to label the product as a “Soft-Melt” tablet; indicating that the consumer may need to bite into the tablet to facilitate quicker disintegration. Figure 3a. Compaction Profile for Ascorbic Acid Advantol Tablets As with any “Soft-Melt” system, the quantity of Advantol required in a formulation will depend on the type and level of active per tablet. Initial studies should be carried out on
your potential formulation by varying the Advantol 200 percentage from 60% to 95%. Figures 3a and 3b show the effect of varying levels of Advantol 200 with a typically poorly
compactible active - Ascorbic acid. Blends were compressed containing 10%, 20%, and
30% ascorbic acid. The figures show the effect upon compactibility (3a) and oral disintegration time (3b). Figure 3b. ODT as a Function of Tablet Hardness for Ascorbic Acid Advantol Tablets Packaging
The nature of the Advantol product is to absorb water rapidly to allow quick disintegration. Figure 4 illustrates the adsorption and desorption properties of Advantol 200 at 25°C. These hygroscopic properties therefore demand attention to packaging. For Advantol based tablets, Aclar® PCTFE* fluropolymer films are recommended as blister material and aluminum foil laminated with child resistant, peel-off paper backing for the lidding. When Advantol based products are packaged in bottles, HDPE bottles with induction sealing and desiccant are recommended. If the packaging or sealing is inadequate, tablet hardness will decrease resulting in higher friability of tablets. Figure 4. Adsorptive and Desorptive Properties of Advantol
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