Effect of Polyox™ Molecular Weight on Drug Release and Physicochemical Properties of Liquisolid and Physical Mixture Formulations

The liquisolid (LS) technique is a relatively recent approach for developing sustained-release dosage forms. This study investigated the effect of Polyox™ molecular weight (MW) on the physicochemical properties and drug-release behavior of LS formulations containing the highly water-soluble model drug diltiazem (DTZ) HCl, using corresponding physical mixture (PM) formulations for comparison. LS formulations were prepared using polysorbate 80 as the liquid vehicle and different grades of Polyox™. Higher-MW Polyox™ grades generally produced slower drug-release profiles than lower-MW grades in both LS and PM matrixes. Based on the release exponent ( n ), LS formulations containing Polyox™ grades up to and including WSRN1105 (MW = 9 × 10 5 ) exhibited Case-II or Super Case-II-type transport, whereas formulations containing WSR301 (MW = 40 × 10 5 ) and WSR303 (MW = 70 × 10 5 ) exhibited anomalous transport. Thus, the observed transition in release mechanism occurred between Polyox™ MWs of 9 × 10 5 and 40 × 10 5 . Similarity-factor analysis indicated that LS formulations containing Polyox™ with MWs ≤ 3 × 10 5 had release profiles similar to their PM counterparts, whereas formulations containing Polyox™ with MWs ≥ 9 × 10 5 showed greater release retardation and dissimilar release profiles. Physicochemical analysis showed that LS formulations containing Polyox™ with MWs below 9 × 10 5 generally had larger particle size distributions, more irregular particle morphology, and lower bulk and tapped densities than their PM counterparts. LS formulations containing Polyox™ with MWs ≥ 9 × 10 5 also exhibited lower net electrostatic charge than the corresponding PM formulations, which may influence powder-handling behavior. Solid-state analyses revealed no detectable drug–Polyox™ interactions. Overall, higher-MW Polyox™ grades, particularly those with MWs ≥ 9 × 10, 5 and provided greater retardation of DTZ release from LS tablets, while the transition in the n-based release mechanism occurred between 9 × 10 5 and 40 × 10 5 .