Pharmaceutical Manufacturing Handbook: Production and

1200 ORAL EXTENDED-RELEASE FORMULATIONS
TABLE 1 FDA Registered Oral ER Formulations Containing Commonly Used
Excipients in Insoluble Matrix Formulations
Excipient
Lipid based
Number of Hits on
FDA Homepage
Carnauba wax
9
Stearyl alcohol
4
Glyceryl behenate
3
Castor oil
2
Cottonseed oil, hydrogenated
2
Cetyl alcohol
2
Paraffi n
2
Stearic acid
2
Castor oil, hydrogenated
1
Vegetable oil, hydrogenated
1
Mineral oil
1
Microcrystalline wax
Insoluble polymer
0
Ethylcellulose
9
Ammonia methacrylate copolymer
5
Polyvinyl acetate
1
Polyethylene
Inorganic
0
Calcium phosphate (dibasic)
6
Source : http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm .
Content Interval (mg)
46 – 300
25 – 244
15 – 51
23
58 – 402
44 – 59
50 – 150
26 – 180
295 – 410
228
15 – 309
37 – 138
46
33 – 335
exposure of lipid - based formulations to erosion, which can be the result of enzymatic
degradation of the lipids [38] . This will of course also infl uence the drug
release rate.
In the compositions of insoluble matrix systems, excipients other than the carrier
material are needed to obtain products with processability and that meet requirements
from the pharmacopedias. Examples of categories of excipients included in
insoluble matrix tablets are binders, lubricants, glidants, colorant, taste maskers,
and channeling agents. As mentioned above, the drug release rate can be regulated
by the porosity in the insoluble matrix system. The properties and amounts of drugs
and excipients that can create pores will have a large impact on the release rate.
Examples of channeling agents are sugars, salts such as sodium chloride, and polyols
[2] . The pore structure also depends on other factors such as the particle sizes of
the excipients and the drug, the size and porosity of the granules, and the compaction
pressure.
The choice of process steps depends on the properties of the drug and the chosen
excipients. For insoluble matrix tablets one often mixes the active substance with
the excipients. Either this mixture can be directly compressed to matrix tablets or
the powder mixture can be exposed to a granulation technology to enlarge the
particle sizes. One such technique is dry granulation, that is, compaction of the
mixture in, for example, a roller compactor, followed by milling to desirable granule
sizes. Another granulation technique is melt granulation, where the melted granulation
liquid agglomerates the particles to granules. The most common granulation