Water-delivery system.
The agglomeration stage is critical in the MADG process and depends on the characteristics of the drug, type and amount of
binders and fillers, and the addition of water. Because the amount of water used in the MADG process is small (e.g., 1–4%),
it is important that the water be delivered accurately and distributed uniformly during the agglomeration stage. The selection
of a spray system that provides accurate delivery and a well-defined spray pattern is important. A suitable spray system,
Schlick MADG Spray Kit, is available for laboratory use from Orthos Liquid Systems (Buffton, SC).
The preferred mechanism to deliver water spray consistently would be an airless spray system, which enables the water to be
directed onto the powder bed in a high-shear granulator. Any airless spray nozzle with a gear pump or pressure vessel, where
the spray pattern can be reproduced and the exact amount of water delivered, would be adequate. Spray nozzles with an orifice
of 0.1 mm or 0.15 mm can be attached to a syringe to deliver a low (5–10 mL) volume of water for small experiments.
Selection of the granulator for the MADG process.
Although it has been reported that a simple planetary blender can be used for the MADG process, the authors believe that
a high-shear granulator would be more suitable for the process (1). An ideal high-shear granulator has efficient impellers
or blades and choppers to allow good mass movement and proper mixing. It also allows water to be sprayed only on the powder
bed and not on the blades, choppers, or granulator wall. Also, the blades and bowl configuration should be such that they
would not allow wet pockets or dead spots to remain after the moisture-distribution or absorption stages. Additional sifting
or sizing of the granulation is required if such pockets or spots form. In other words, if good water distribution is achieved,
further granulation sifting or sizing is unnecessary. Using this approach, the authors have successfully manufactured various
products at batch sizes ranging from 100 g to 30 kg using equipment such as Bohle, Diosna, Fuji, Collette, or PMA Aeromatic-Fielder
high-shear granulators.
Granulation sizing and milling.
An optimized MADG formulation and process should not produce large lumps in the granulation that require sizing or milling.
Therefore, once lubricant is blended in with the granulation, the result may be the final blend that can be directly used
for tablet compression, encapsulation, or powder filling. At times, small amounts of lumps in the granulation may stem from
material buildup on the blades, choppers, walls, or the bottom of the granulator during agglomeration. In such situations,
it may be necessary to pass the granulation through a screen such as 10 mesh or any other suitable size. Often, sizing or
sifting is needed only if the formulation or process contains imperfections.
Note
MADG process-based formulation-development studies carried out with various pharmaceutical compounds will be described in
Part II of this article, which will appear in the December 2009 issue of Pharmaceutical Technology.
Ismat Ullah is president of Simple Pharma Solutions (Cranbury, NJ). Jennifer Wang* is a senior research investigator, Shih-Ying Chang is a principal scientist, Gary J. Wiley is a retired research scientist, Nemichand B. Jain is a director of biopharmaceutics research and development, and San Kiang is a research fellow, all at Bristol–Myers Squibb, 1 Squibb Dr., New Brunswick, NJ 08903, tel. 732.227.5684, jennifer.wang@bms.com
*To whom all correspondence should be addressed.
Submitted: Jan. 15, 2009. Accepted: Feb. 23, 2009.
What would you do differently? Submit your comments about this paper in the space below.
References
1. I. Ullah et al., Pharm. Technol.
11 (9), 48–54 (1987).
2. C. Chen et al., Drug Dev. Ind. Pharm.
16 (3), 379–394 (1990).
3. L.H. Christensen, H.E. Johansen, and T. Schaefer, Drug. Dev. Ind. Pharm.
20 (14), 2195–2213 (1994).
|
