Dataset Information

Application of Ultra-Centrifugation and Bench-Top 19F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products.

ABSTRACT: Generic drug products are expected to have the same active pharmaceutical ingredient (API) (Q1) with the same content (Q2) and microstructure arrangement (Q3) as the innovator product. In complex oil-in-water emulsion drugs, the hydrophobic API is mainly formulated in oil droplets stabilized by surfactant and micelles composed of extra surfactant molecules. The API phase partition in oil and water (mainly micelle) is a critical quality attribute (CQA) of emulsion product in demonstrating physicochemical equivalence using difluprednate (DFPN) emulsion product Durezol® as a model, we developed a novel low-field benchtop NMR method to demonstrate its applicability in measuring DFPN phase partition for ophthalmic oil-in-water emulsion products. Low-field 19F spectra were collected for DFPN in formulation, in water phase and oil phase after separation from ultra-centrifugation. The NMR data showed the mass balance of DFPN before and after phase separation. The average water phase content of different Durezol® lots was 32 ± 3% with 1% variation from method reproducibility test. The partition results were 52 ± 2% for the in-house control products prepared in Q1/Q2 equivalence to Durezol® but by a different process. The significant difference in DFPN-phase partition between Durezol® and the in-house formulation demonstrated manufacture difference readily changed the API partition. The newly developed ultra-centrifugation and 19F NMR by benchtop instrument is a simple, robust, and sensitive analytical method for ophthalmic emulsion drug product development and control.

SUBMITTER: Wang X

PROVIDER: S-EPMC6995277 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Application of Ultra-Centrifugation and Bench-Top <sup>19</sup>F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products.

Wang Xinyi X Patil Sharadrao M SM Keire David A DA Xu Xiaoming X Chen Kang K

AAPS PharmSciTech 20180302 4

Generic drug products are expected to have the same active pharmaceutical ingredient (API) (Q1) with the same content (Q2) and microstructure arrangement (Q3) as the innovator product. In complex oil-in-water emulsion drugs, the hydrophobic API is mainly formulated in oil droplets stabilized by surfactant and micelles composed of extra surfactant molecules. The API phase partition in oil and water (mainly micelle) is a critical quality attribute (CQA) of emulsion product in demonstrating physico ...[more]

PMID: 29500761

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Project description:BackgroundThe assessment of spinal stiffness by manual palpation in clinical settings has demonstrated both poor accuracy and reliability. More recently, mechanical methods for assessment of spinal stiffness have demonstrated superior accuracy and reliability. However, mechanical methods of spinal stiffness assessment can be expensive, time consuming and/or unsuited to clinical practice. While a new device has been designed to address these issues (VerteTrack), its benchtop performance remains unknown.AimTo measure the bench-top performance of VerteTrack.MethodsA series of laboratory-based experiments were conducted in February 2018 to investigate the accuracy (precision and bias) of load and displacement measurements obtained by VerteTrack and then were compared against an appropriate reference standard. Measurements of both multiple-level continuous assessment (multiple spinal levels measured), and single-level assessment (single spinal level measured) were performed on a viscoelastic foam medium (AIREX® balance beam, Switzerland) and the resulting stiffness calculated.ResultsVerteTrack demonstrated high precision at all loads and displacements. There was minimal systematic measurement bias identified for applied versus reference load (mean bias = - 0.123 N; 95%CI - 0.182 to 0.428 N, p < .001), and no systematic measurement bias for measured versus reference displacement (mean difference = 0.02 mm; 95%CI - 0.09 to 0.14 mm, p < .001). The magnitude of stiffness obtained during multiple-level continuous assessment was on average 0.25 N/mm (2.79%) less than that for single-level assessment (95%CI - 0.67 to 0.17 N/mm, p < .001).ConclusionsVerteTrack demonstrated high accuracy (high precision, low bias) under bench-top conditions. The difference in stiffness found between multiple versus single spinal levels should be considered in the research context, but is unlikely to be clinically relevant. The results of this study demonstrate that VerteTrack may be suitable for both single and multi-level spinal stiffness measurements in-vivo.

Dataset Information

Application of Ultra-Centrifugation and Bench-Top 19F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products.

Publications

Application of Ultra-Centrifugation and Bench-Top <sup>19</sup>F NMR for Measuring Drug Phase Partitioning for the Ophthalmic Oil-in-Water Emulsion Products.

Similar Datasets

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