Robustness in pharmaceutical solid oral dosage forms means consistently providing the same drug-dissolution performance and
shelf life from the dosage form when manufactured within the limits of the defined variations of key quality parameters, which
include excipients, active pharmaceutical ingredients (APIs), and the manufacturing process. Under ideal circumstances, formulators
would have available to them excipients with a broad range of properties with which to assess the impact of excipient variability
on the formulation robustness. Realistically, however, the ability of the supplier to manufacture products at the extremes
of a product specification is challenging given that manufacturing processes are designed to operate under optimal process
conditions to produce a consistent product.
For polyethylene oxide (PEO), blends may be the answer. When formulating PEO-based matrix systems, the key polymer attributes
that affect drug dissolution are polymer viscosity and particle-size distribution. Because PEO does not have the additional
complication of chemical substitution seen with many other excipients, blending is a straightforward approach for producing
samples for formulation studies, provided the performance of the blended polymer mixture is representative of the standard
product. PEO blends can provide a range of samples across a viscosity specification to achieve the necessary variability in
product viscosity more easily than using batches of a single PEO product. These samples can then be used to assess the impact
of product viscosity variability on formulation properties. This study used two standard PEO products—Polyox 205 National
Formulary (NF) water-soluble resins (WSR) and Polyox N-12K NF WSR (Dow Chemical, Midland, MI)—to develop a series of samples
across the viscosity-specification range of another standard product, Polyox 1105 NF WSR, which has a viscosity between these
two grades. Polymer viscosity, molecular weight, tablet hardness, and drug dissolution were measured to determine the effect
of PEO blends on excipient performance in extended-release matrix tablets.
Materials. Excipients used for blending included Polyox 205 NF WSR and Polyox N-12K NF WSR (The Dow Chemical Company) with approximate
molecular weights of 6 x 105 and 1 x 106 Da, respectively. Excipients used as standards for comparison were three samples of Polyox 1105 NF WSR (The Dow Chemical
Company) with varying solution viscosities with an approximate molecular weight of 9 x 105 Da. The APIs were theophylline and diltiazem hydrochloride (HCl) (Spectrum Chemicals and Laboratory Products, Gardena, CA).
Other ingredients included microcrystalline cellulose (MCC, Avicel PH 102, FMC Biopolymer, Newark, DE) and magnesium stearate
(Spectrum Chemicals and Laboratory Products).
Table I: Viscosity of polyethylene oxide samples.
Methods. Three blends (25/75, 50/50, and 75/25) were prepared with Polyox 205 NF WSR and Polyox N-12K NF WSR using a mixer (Turbula
T2F Heavy Duty Shaker–Mixer, Glen Mills, Clifton, NJ). Viscosity determinations for PEO samples were made using a digital
viscometer (Brookfield DV-II+ viscometer, Brookfield Engineering Laboratories, Middleboro, MA), 5% aqueous solution, with
spindle 2 at 2 rpm, except for the sample of Polyox N-12K NF WSR, which was run at 2% aqueous solution, spindle 1 at 10 rpm.