In Vitro Dissolution Profiles Similarity Assessment in Support of Drug Product Quality: What, How, When—Workshop Summary Report

Suarez-Sharp, Sandra; Abend, Andreas; Hoffelder, Thomas; LeBlond, David; Delvadia, Poonam; Kovács, E.; Diaz, Dorys Argelia

doi:10.1208/s12248-020-00458-9

Cited by 26 publications

(11 citation statements)

References 18 publications

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“…Nevertheless, all plotted dissolution data from 0 to 90 min show stage one and stage two time points. The authors understand that there is no scientific consensus on several aspects performing f 1 and f 2 profile similarity factors . Accordingly, these factors were applied in individual stages of two-stage dissolution profiles generated in the present study.…”

Section: Resultsmentioning

confidence: 86%

“…The authors understand that there is no scientific consensus on several aspects performing f 1 and f 2 profile similarity factors. 42 Accordingly, these factors were applied in individual stages of two-stage dissolution profiles generated in the present study. The f 1 and f 2 results (Table 3) were consistent with the dissolution profiles reported in Figure 7.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach

2021

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The current research work focuses on understanding the reported discrepancies and our observations in the dissolution profiles of warfarin sodium tablets and potential patient-based failure modes during oral warfarin therapy. It was hypothesized that freely soluble crystalline warfarin sodium (WARC) at first transforms into noncrystalline warfarin sodium (WARNC) under stress conditions. The WARC → WARNC conversion facilitates the rapid formation of the poorly soluble unionized form, which could lead to dissolution failures and potential poor in vivo performance. Depressed warfarin concentrations locally in the gastrointestinal tract (GIT) may in turn lead to inadequate absorption and thereby affect bioavailability. A low volume two-stage dissolution method was developed to mimic in vivo GIT conditions. Warfarin sodium tablets exposed to room temperature and 75% relative humidity for 1 week showed approximately 23% decrease in drug release. The decline in drug release supports the hypothesis that WARNC is converted to the unionized form faster than WARC does under the same conditions. Solid state characterization (powder X-ray diffractometry and differential scanning calorimetry) data demonstrated the disproportionation of warfarin sodium to unionized warfarin after solubility and dissolution studies. The findings support the hypothesis and a possible failure mode of warfarin sodium tablets. This work is a second case study from our laboratory on narrow therapeutic index drug products in which the instability of the solid state of the drug substance is potentially responsible for observed clinical failures.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach

2021

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“…Dr. For prediction of an overall profile, one can also evaluate f 1 and f 2 , the difference and similarity factors, although there is a great deal of debate and discussion as to the applicability of these factors and the situations in which they are relevant, as well as alternative methods of comparing dissolution profiles (29)(30)(31).…”

Section: Model Selection and Developmentmentioning

confidence: 99%

Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation - Workshop Summary Report

Zaborenko¹,

Carducci²,

Ryckaert³

et al. 2022

Dissolution Technol.

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To date, few examples of dissolution models for real-time release testing (RTRT) have been approved for commercial drug products or published in literature. Thus, a structured approach has not been established by which a novice to the field could design, develop, validate, and implement an RTRT dissolution model. Moreover, with scant examples available, there has not been a body of work by which to learn of general regulatory expectations for such models.To address these gaps and to encourage conversation between regulatory and industrial experts on these topics, a virtual (web-based) workshop entitled "Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation" was held November 11-12, 2021. This article summarizes key points from the podium presentations, panel discussions, and breakout sessions focusing on (1) the current best practices to establish predictive model specifications; (2) designing models to predict the "safe space" of a release test and creating models utilizing process analytical technology (PAT); and (3) exploring the strategy of compliant regulatory submissions, including model validation and post-approval lifecycle management. Industrial case studies were presented showcasing attempted approaches to and successful implementations of RTRT of dissolution for drug product manufacturing.

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“…In addition, the use of this technique for BCS class II drugs is complicated because there are difficulties in choosing the medium for dissolution [13]. Inconsistency in rules and criteria between different countries, differences in the interpretation of test results for assessing the similarity of dissolution profiles is another key point that complicates this procedure and does not allow its use for rapid pilot identification of anomalous lots of generic nimesulide drugs [14,15]. Till date, only few works have been published in the available literature on methods of pilot discriminant analysis of generic nimesulide granules for oral suspension, which would allow rapidly and without the use of equipment for hundreds of thousands of dollars to detect differences between lots of generic and original drugs and send suspected or anomalous lots for additional complex abovementioned studies.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A survey and optical microscopy in pilot comparative analysis of generic and original nimesulide granules

Leonenko

Ostanina

Kokoieva

et al. 2021

Heliyon

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Background: Secondary to increased development of generic nonsteroidal anti-inflammatory drugs (NSAIDs), there is a lack of simple and inexpensive ways of pilot detection of differences between the batches of generic drugs and the original ones. Objectives: To determine the peculiarities of the use of generic NSAIDs in routine practice through a pilot survey of dentists and to conduct a pilot comparative analysis of generic and original NSAIDs containing nimesulide granules using optical microscopy. Methods: The first part of the study included a pilot survey Convenience sampling of 192 dentists to study the use of generic NSAIDs in their routine practice. The second part included the use of a pilot optical microscopy of nimesulide particles isolated from four drugs: original drug (NA) and generic ones (NB, NC, ND). Results: In the questionnaires, dentists pointed to a 68.7% lower clinical efficacy and a 62.6% higher percentage of side effects of generic NSAIDs compared to the original ones. Based on the results of pilot optical microscopy, a statically significant difference in the size distribution of the drug substance particles in all generic nimesulide granules was determined as follows: NB (χ 2 : 15.15; p < 0.01); NC (χ 2 : 11.09; p < 0.05); ND (χ 2 : 1625.34; p < 0.001) compared with the original drug NA. Conclusions: A pilot survey of dentists showed that doctors noted the practical difference in the effects of the original and generic NSAIDs. A significant difference in the size of nimesulide particles and their distribution in generic drugs NB, NC, ND compared to the original NA suggests a possible difference in bioavailability and bioequivalence.

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In Vitro Dissolution Profiles Similarity Assessment in Support of Drug Product Quality: What, How, When—Workshop Summary Report

Cited by 26 publications

References 18 publications

Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach

Molecular Insights into Warfarin Sodium 2-Propanol Solvate Solid Form Changes and Disproportionation Using a Low Volume Two-Stage Dissolution Approach

Predictive Dissolution Models for Real-Time Release Testing: Development and Implementation - Workshop Summary Report

A survey and optical microscopy in pilot comparative analysis of generic and original nimesulide granules

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