Excipients in Polymeric Drug Delivery and Formulations - Pharmaceutical Technology

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Excipients in Polymeric Drug Delivery and Formulations
A roundtable with John Doney, Jiao Yang, Hans Baer, and Elena Draganoiu.

Pharmaceutical Technology

Carbomer combinations in controlled-release matrix tablets

Draganoiu: 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 extension.

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 Corporation.


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