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Background: The replacement of traditional oils with a camphor and menthol-based eutectic mixture is done to prepare oil-less emulsion-like dispersions for co-delivery of cinnarizine (CNZ) and morin hydrate (MH) for managing Meniére's disease (MD). Since two drugs are loaded into the dispersions, the development of a suitable reverse phase-high performance liquid chromatography (RP-HPLC) method for their simultaneous analysis becomes inevitable.
Objective: By applying the analytical quality by design (AQbD) approach, the RP-HPLC method conditions were optimized for the concomitant determination of two drugs.
Methods: The systematic AQbD started with identifying critical method attributes (CMA) through an Ishikawa fishbone diagram, risk estimation matrix, and risk priority number-based failure mode effect analysis followed by screening using fractional factorial design and optimization by face-centered central composite design. The concomitant determination of two drugs by the optimized RP-HPLC method condition was substantiated via specificity checking using combined drug solution, drug entrapment efficiency, and in vitro release of the two drugs from emulsion-like dispersions.
Results: The AQbD optimized RP-HPLC method conditions revealed the retention time for CNZ and MH at 5.017 and 5.323, respectively. The studied validation parameters were found within the ICH-prescribed limits. Exposing the individual drug solutions to acidic and basic hydrolytic conditions yielded extra chromatographic peaks for MH, probably due to the degradation of MH. The DEE % values of 87.40 ± 4.70 and 74.79 ± 2.94, respectively, were noticed for CNZ and MH in emulsion-like dispersions. More than 98% CNZ and MH release was occurred from emulsion-like dispersions within 30 min post-dissolution in artificial perilymph.
Conclusions: Overall, the AQbD approach could be helpful for systematic optimization of RP-HPLC method conditions to estimate concomitantly other therapeutic moieties.
Highlights: The proposed article shows the successful application of AQbD for the optimization of RP-HPLC method conditions to concomitantly estimate CNZ and MH in combined drug solution and dual-drug-loaded emulsion-like dispersions.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1093/jaoacint/qsad068 | DOI Listing |
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