Abstract

Abstract

Primary packaging can be a critical determinant of performance for semisolid drug products, particularly when the dose is delivered by a metered device. This study evaluated an airless, pouch-based metered-dose dispenser (Topi-pump™) as a container–closure and dose-delivery system for topical semisolids, focusing on (i) packaging quality attributes, (ii) delivered-dose reproducibility, and (iii) compatibility during in-use/accelerated conditions. Packaging performance was assessed by UV–Vis light transmission (opacity), aqueous extractables screening by UV–Vis, and particulate contamination testing. Dose delivery was benchmarked against two comparable calibrated airless dispensers by quantifying the dispensed mass of semisolid vehicles under predefined handling conditions (orientation and temperature) over 10 days. The schedule comprised 40 recorded actuations per dispenser and did not extend to container exhaustion, so terminal-dose behavior was not characterized. Dispensed mass was evaluated against a 0.5 g ± 5% criterion. Compatibility was examined using model semisolids containing representative steroidal drug substances, compounded in multiple cream bases, under accelerated storage conditions, supported by microbiological testing guided by USP <61>/<62> and acceptance criteria from USP <1111>. The dispenser met predefined packaging criteria, showing low extractables (0.0050 AU; limit =0.20 AU), low particulate burden (largest particle 67 µm; criterion =100 µm), and low light transmission (opacity 0.15%; criterion =1.0%). In the pooled screening across all vehicles and operating conditions, the Topi-pump™ dispenser showed a mean dispensed mass closest to the nominal target and the lowest overall variability by coefficient of variation (screening CV 9.5% vs 18.6–21.2% for comparators), although pooled interquartile ranges were comparable for Topi-pump™ and Pump A, suggesting that the difference reflected observations outside the central portion of the distributions rather than central dispersion. Condition-level conformity and precision were subsequently evaluated within Pentravan® as a single fixed reference matrix, with apparent viscosity considered as part of the formulation context.with apparent viscosity considered as part of the formulation context. In the preliminary vehicle-level screening, using combined data from all three dispensing systems and all evaluated temperature–orientation conditions, observed conformity was 61.4% for Pentravan®, 46.2% for Fitalite™ (Phytobase™), 39.4% for HRT Heavy™, and 7.7% for Salt Stable™ LS Advanced. These proportions pool three devices, three temperatures and three orientations against a ±5% band, and in the most viscous vehicle they reflect a systematic offset rather than erratic delivery: in Salt Stable™ LS Advanced (96.4 Pa·s at 20 °C), Topi-pump™ delivered a median of 0.450 g per actuation with a robust coefficient of variation of 6.7%, comparable to its precision in the other vehicles evaluated, and conformity in that matrix reached 98.1% against the 75–125% individual-dose interval applied in earlier work. Drug assay remained within 90–110% of the label claim throughout the study period, with TAMC/TYMC below the reporting limit (<10 CFU/g) and the specified pathogens absent. Across the tested conditions, the airless metered-dose pouch system met the predefined container–closure acceptance criteria. It showed the lowest conventional coefficient of variation in the pooled screening and low within-condition variability in the focused Pentravan® analysis, indicating suitable performance as a delivery platform for compounded topical semisolids under these conditions.

Related Keywords

• Carolina Souza de Barros Gomes Anna
• Schettino Kegele Carolina
• Taylor Sarah
• Polonini Hudson
• Primary Packaging
• Metered-dose Dispenser
• Topical Semisolids
• Dose Uniformity
• Container–closure System
• Topi-pump
• Airless Packaging
• Compounded Preparations

Related Categories

• PEER-REVIEWED
• TECHNOLOGY
• PATIENT COMPLIANCE