(M0930-03-18) Evaluating the Versatility of Klucel™ Xtend HPC in Dual Active Allergy Relief Extended-Release Dosages

Purpose: Dual-active extended-release formulations for allergy relief provide several benefits over single-component products, including reduced dosing frequency, improved seasonal allergic rhinitis (SAR) control with moderate-to-severe nasal congestion symptoms, and improved patient compliance. Common hydrophilic matrix-forming polymers such as Hydroxypropyl Methylcellulose (HPMC) are usually used at 20 to 35 percent by weight of a tablet to achieve an acceptable release profile and also need intra-granular binders to avoid a burst effect when dealing with highly water-soluble drugs. This study evaluates the process versatility and tablet size reduction capabilities of the new hydroxypropyl cellulose (HPC) Klucel™ Xtend, matching the release profile of commercially available Zyrtec-D® (pseudoephedrine HCl 120mg extended-release tablet and cetirizine HCl 5mg per tablet).

Methods: Zyrtec-D was reverse-engineered to identify the level and Mw of the control release polymer, HPMC, and other inactive ingredients (Table 1). The polymer gel strengths of hydrated tablets of the new hydroxypropyl cellulose (HPC) Klucel™ Xtend HPC and hydroxypropyl methylcellulose (HPMC) K100M were determined using a TA Instruments Discovery Hybrid Rheometer (DHR-3) with a Peltier heating stage. To evaluate the impact of various levels of Klucel Xtend HPC, microcrystalline cellulose, and lactose on the properties of pseudoephedrine HCl tablet formulations and their drug release profiles, a three-level full factorial design was employed. This involved creating twelve DOE tablet formulations with Klucel™ Xtend HPC levels ranging from 15% to 25%, microcrystalline cellulose levels from 26% to 40%, and lactose levels between 0% to 11% (as can be seen in Figure 1). Following this, each monolayer core tablet was coated with a barrier layer, then with a drug layer of cetirizine HCl utilizing a Freund Vector LDCS® Tablet Coater, before being cosmetically film-coated. All tablets were characterized for dimensions, hardness, friability, and dissolution release profiles. Dissolution testing of each formulation was conducted in 900 mL of DI water maintained at 37°C with USP Apparatus 1 (baskets) at 100 RPM. Samples were taken at intervals of up to 12 hours; quantitation was by HPLC with UV detection for both drugs.

Results: Total Hydroxypropyl Methylcellulose (HPMC) is up to 35 percent by tablet weight. The new hydroxypropyl cellulose (HPC) Klucel™ Xtend HPC had six times greater gel strength than HPMC, indicating a stronger gel matrix. Due to the stronger gel, the Cetirizine HCl / Pseudoephedrine HCl extended-release tablets formulated with new hydroxypropyl cellulose (HPC) Klucel™ Xtend required significantly lower controlled release polymer (20%). The lower use level enabled smaller and slightly stronger tablets than Zyrtec-D. With a 15% thinner and 10 % total volume reduction, the tablet formulations with Klucel™ Xtend HPC are likely to have better consumer compliance and lower production costs than commercial tablets. Also, Cetirizine HCl / Pseudoephedrine HCl tablets with Klucel™ Xtend HPC showed comparable drug release to marketed Zyrtec-D with a similarity factor of 82 at similar tablet hardness (Figure 2).

Conclusion: Although HPMC is a commonly used polymer for controlled release, it may not be the best option for highly water-soluble drugs. The introduction of Klucel™ Xtend, a new hydroxypropyl cellulose, provides a promising solution with superior gel strength. This innovative polymer can significantly reduce the burst effect during drug delivery and allows for reduced polymer usage levels, resulting in smaller tablet sizes while maintaining a similar dissolution profile to commercial tablets. Despite HPMC's continued popularity, Klucel™ Xtend HPC's functionality makes it a game-changer for highly soluble drugs.


Figure 1: Experimental design


Table 1: De-formulation results of Zyrtec-D tablet


Figure 2: Dissolution of Zyrtec-D® compared to Cetirizine HCl / Pseudoephedrine HCl extended-release with 20% Klucel Xtend HPC in the Pseudoephedrine HCl extended-release core.