Carbomer combinations in controlled-release matrix tablets
Carbomers are highly efficient gel-matrix formers for controlling drug release in tablets, capsules, and multiparticulate
systems. In many cases carbomers have demonstrated slower drug-release rates at lower concentrations than other commercially
available excipients, enabling overall formulation cost savings and smaller tablet sizes. Additionally, tablet formulations
using carbomers have demonstrated excellent hardness and low friability over a wide range of compression forces. Carbomers
can enable scientists to develop patentable technologies that offer the benefits of product differentiation and/or life-cycle
Carbomers are widely compatible with commonly used tablet ingredients and can be used alone or in combination with other extended-release
excipients (e.g. hypromellose, hydroxypropyl cellulose, sodium alginate) to achieve a desired release profile. Select carbomers
are available in both powder and granular forms; therefore, they can be used in all types of tablet-manufacturing processes.
A free-flowing granular product is available for use in direct-compression processes.
A new concept in controlled release is the use of carbomer combinations that allow formulators to include the polymer both
intra- and extra-granularly. This approach provides flexibility in achieving target release profiles. An example is the use
of a combination of powder-grade ("Carbopol" 971P NF, Lubrizol, Wickliffe, Ohio) and granular-grade ("Carbopol" 71G NF) carbomer
homopolymers in a metoprolol extended-release formulation.
The powder-grade polymer and active drug were incorporated by wet granulation and the resulting granules blended with the
granular-grade polymer. Use of carbomers both intra- and extra-granularly enables inclusion of a higher total polymer level
compared with the amount of carbomer that can be used in wet granulation without affecting the processability of the wet mass.
Intra-granular addition of the powder-grade polymer allows more efficient drug release at lower polymer levels than direct
compression with the granular-grade polymer alone (lower cost; smaller tablets). The difference in hydrogel formation and
controlled-release performance is a result of the larger surface area of the powder-grade carbomer compared with the granular-grade
carbomer. This approach allows for formulation flexibility by varying total polymer level and the intra-versus extra-granular ratio.
By combining both types of carbomers, it is possible to achieve a desirable balance with regard to processing (generally easier
at lower polymer levels) and controlling drug release (more efficient at higher polymer levels).
Metoprolol extended-release tablets were successfully formulated using a combination of carbomers. Various inclusion levels
of the powder-grade and granular-grade polymers for two formulations were used. One formulation (Formulation A) contained
an intra-granular addition of 6% weight/weight (w/w) of the powder-grade carbomer homopolymer (Carbopol 971P NF) and an extra-granular
addition of 24% w/w of the granular-grade carbomer homopolymer (Carbopol 71G NF). The second formulation (Formulation B) contained
an intra-granular addition of 8% w/w of the powder-grade carbomer homopolymer (Carbopol 971P NF) and an extra-granular addition
of 24% w/w of the granular-grade carbomer homopolymer (Carbopol 71G NF).
The active drug, powder-grade polymer, and filler were mixed and granulated with deionized water. The resulting granules were
blended with granular-grade polymer then with the glidant and the lubricant, and compressed at target weight and hardness.
Formulations A and B met US pharmacopeial requirements and matched the release profile of the reference commercial product.
The carbomer combination in these formulations provided easier handling during the wet-granulation process and enabled less
complex processing compared to other extended-release technologies.
Elena Draganoiu, PhD, is a senior research and development pharmacist in the Pharmaceutical Ingredients business of The Lubrizol