Using Polyethyline Oxide Blends to Assess the Effect of Excipient Variability - Pharmaceutical Technology

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Using Polyethyline Oxide Blends to Assess the Effect of Excipient Variability
The authors discuss a study that demonstrates the use of polyethylene oxide mixtures to investigate the effect of polymer viscosity on formulation robustness.


Pharmaceutical Technology
Volume 33, Issue 12


Table III: Tablet hardness for theophylline formulations containing polyethylene oxide (PEO) compared with formulations containing PEO blends.
Effect of blending on molecular weight. Several questions can arise concerning blends of materials that contain different molecular weights. Will the blend have a bimodal distribution or show a tailing effect at the high end? Will such differences in molecular weight have the potential to affect other formulation properties?


Table: IV: Tablet hardness for formulations of diltiazem hydrogen chloride containing polyethylene oxide (PEO) compared with formulations containing PEO blends.
Table II shows the molecular-weight data obtained via SEC–MALLS for the Polyox 1105 NF WSR samples, the Polyox 205 NF WSR and Polyox N-12K NF WSR blend components, and the blends. The weight-average molecular-weight values of the blends were between the values for each component, decreasing with increasing amounts of the lower weight-average molecular-weight component (Polyox 205 NF WSR). Standard deviations for the blends were < 1.6%. The weight-average molecular-weight values of the Polyox 1105 NF WSR samples were very similar, with standard deviations of < 0.36%. These standard deviations indicate excellent reproducibility for the SEC-MALLS measurement. A comparison of the approximate molecular weight of standard Polyox WSR samples provided in product literature (viscosity-average molecular weight) to the molecular weight determined by SEC-MALLS (weight-average molecular weight) shows significantly higher values for the SEC measurement. As discussed by Flory (1), viscosity-average molecular weight should be greater than number-average molecular weight and less than weight-average molecular weight for polymers with a polydispersity > 1. This principle explains why molecular-weight data in product literature is not directly comparable to results obtained by SEC-MALLS.


Figure 3: Drug dissolution for theophylline formulations containing polyethylene oxide compared with formulations containing polyethylene oxide blends. (FIGURE COURTESY OF THE AUTHORS)
Molecular-weight distribution obtained from SEC-MALLS showed little difference between Polyox 1105 NF WSR individual samples and both the Polyox 205 NF WSR and POLYOX N-12K NF WSR blend components or the blends themselves. PEO showed a broad molecular-weight distribution regardless of polymer molecular weight (see Figure 1). The molecular-weight distribution can vary to some degree for a specific PEO product as observed for Polyox 1105 NF WSR where PDI ranged from 4.52 to 5.74 (see Table II). The molecular-weight distributions for Polyox 205 NF WSR and Polyox N-12K NF WSR blend components were similar to that of Polyox 1105 NF WSR (see Figure 1). Blends of Polyox 205 NF WSR and Polyox N-12K NF WSR also had molecular-weight distributions similar to Polyox 1105 NF WSR (see Figure 2). Neither bimodality nor high-end tailing was observed in the blends. The SEC-MALLS results showed that blending of Polyox NF WSR product grades adjacent to the targeted Polyox product grade does not adversely impact molecular-weight distribution.


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