Pharmaceutical Manufacturing Handbook: Production and

TABLE 2 FDA Registered Oral ER Formulations Containing Commonly Used
Excipients in Hydrophilic Matrix Tablets
Hydrophilic Polymer
a
Hydroxypropyl methyl
cellulose [24]
Hydroxypropylcellulose
[120, 121]
Polyethylene oxide [68, 128]
Sodium alginate [134]
Xanthan gum [125, 137 – 140]
Hydroxyethyl cellulose
[117 – 119]
Carbomer [129]
Methyl cellulose [121]
shown that degradation of PEO to lower molecular weight might occur due to the
high temperature used in the extruder. Extrusion to small pellets based on hydrophilic
polymers hydroxyethyl cellulose (HEC) and HPMC has been performed, and
isopropyl alcohol instead of water was used to avoid lump formation [12] . Also
Carbopol [14 – 16] , pectin [114] , and xanthan [115, 116] have been extruded and used
as matrix carrier materials for extended release.
The choice of hydrophilic polymer is one determining factor for the drug release
rate, as discussed above. The most common type used for hydrophilic matrix systems
is HPMC (hypromellose, hydroxypropyl methyl cellulose) [24, 83] but some alternatives
are HEC [117 – 119] , HPC [120, 121] , methyl cellulose [121] , xanthan [122 – 127] ,
PEO [68, 128] , Carbopol [129 – 131] , pectin [131 – 133] , and alginate [134 – 136] ; see
Table 2 . HPMCs are available in several approved degrees of substitution [60] . To
achieve different release durations, different viscosity grades of the polymers may
be used (the higher the viscosity grade, the slower the release rate). If the desired
viscosity is not available, one can mix two polymer grades with different viscosity
grades [68] .
6.8.5
COMPARISON AND SUMMARY OF DIFFERENT TECHNOLOGIES 1211
Fraction of
Excipient (%)
10 – 80
15 – 35
5 – 85
5 – 50
10 – 99
40 – 97.5
20 – 75
5 – 75
Source : http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm .
a Examples of references using them are given.
Number of Hits on
FDA Homepage
Other Names
of Excipients
COMPARISON AND SUMMARY OF DIFFERENT TECHNOLOGIES
The main principles for oral extended drug release reviewed here are the
membrane - coated reservoir systems and hydrophilic or hydrophobic matrix systems.
They all have advantages and drawbacks and Table 3 summarizes some aspects of
the different formulation principles.
There are a number of commercial variants of the above - mentioned principles.
Examples of commercial matrix - based formulations can be found in a review by
Varma et al. [137] . One of the oldest commercial hydrophilic matrix systems is
12
4
4
3
3
3
1
1
Hypromellose,
HPMC,
MHPC
HPC
PEO
Carbopol,
polyacrylic
acid
MC