Variability of USP Lot P Prednisone Reference Standard Tablets - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Variability of USP Lot P Prednisone Reference Standard Tablets
The authors demonstrate that anecdotal reports of prednisone tablet variability are inaccurate.


Pharmaceutical Technology


Study 1. This study was conducted to compare the dissolution variability of USP Prednisone Lot P RS Tablets to that of four commercially available products (13). Two of the products dissolved so quickly that no meaningful comparison was possible. Reference 13 and the present article thus present data only for ranitidine hydrochloride and metformin tablets compared to the USP Prednisone Lot P Tablets.

Study 1 was a single-laboratory study. Each of the three products was tested by two six-tablet experiments on each of three assemblies configured as Apparatus 2 (paddles), each by two analysts, for a total of 12 experiments. Following log transformation, the variance for each set of six was calculated and pooled over the two experiments. The pooled variance was then converted to the intra-experiment %CV as described above. These intra-experiment %CVs include contributions from, at least, the tablets tested, variability among positions in each assembly, the assay, and the position of the tablet when dropped into the vessel. As conducted, position stands for the physical position as well as the particular combination of shaft, paddle, and vessel used at that position. The "combined" results were obtained by a random-effects ANOVA. The following were included as random effects: assembly, position nested within assembly, analyst, and experiment nested within analyst and assembly. The data were analyzed by SAS Proc Mixed [SAS Inc., Cary, NC]. The residual %CVs thus obtained include contributions from the same sources as for the assembly- and analyst-specific %CVs except for position within the assembly.

Study 2. This study was conducted to evaluate the reproducibility of PVT results following the relocation of equipment between different laboratory sites (16). Dissolution experiments with USP Lot P Prednisone RS Tablets were conducted at two sites (Site 1 and Site 2). Equipment from two manufacturers was used for the experiments. Three dissolution experiments (six tablets per experiment) were repeated by the same two analysts at each of the sites. Experiments were performed at Site 1. The testers were then moved to Site 2, a thorough mechanical calibration was performed, and PVT experiments were repeated. Finally, the equipment was moved back to Site 1, the mechanical calibration was repeated, and PVT experiments were repeated. Vessels, paddles, and shafts were serialized and retained the same position in the instrument throughout the experiments. The reported %CVs were pooled across the three experiments as described for Study 1. Contributions to these intra-experiment %CVs are also as described for Study 1.

Study 3. This study was conducted to evaluate the contributions of analyst and assembly to dissolution results using both Apparatus 1 and Apparatus 2 (2). The study focused on intermediate precision within a single laboratory. Five assemblies were used, each by at least four of six analysts. For each analyst–assembly combination and for each of Apparatus 1 and Apparatus 2, there were six experiments, and each experiment was performed using six to eight tablets, depending on the equipment.

The data were first analyzed by a random-effects ANOVA separately for each assembly. Random effects were position, analyst, and experiment nested within analyst. The %CVs reported are from the residual variance from the ANOVAs. These intra-experiment %CVs include contributions as for the Study 1 ANOVA results, namely from, at least, the tablets tested, the assay, and position of the tablet when dropped into the vessel.

Study 4. This study was conducted to evaluate the relationship between vessel dimensions and dissolution results (12). This was a single-laboratory study, and all work was done by one analyst on one assembly configured as Apparatus 2. Three sets of six vessels were evaluated, and each set was obtained from a different manufacturer. For each set, six dissolution experiments were conducted, and each consisted of six tablets of USP Lot P Prednisone RS Tablets. Following log transform, the variance for each set of six was calculated and pooled over the six experiments for a given vessel manufacturer. The pooled variance was then converted to the intra-experiment %CV as described above. As with Study 1, these intra-experiment %CVs included contributions from, at least, the tablets tested, variability among positions in each assembly, the assay, and the position of the tablet when dropped into the vessel.


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerRelationship-building at Top of Mind for Clients
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerRisk Reduction Top Driver for Biopharmaceutical Raw Material Development
Jill Wechsler Regulatory Watch Jill Wechsler Changes and Challenges for Generic Drugs
Faiz Kermaini Industry Insider Faiz KermainiNo Signs of a Slowdown in Mergers
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Sandoz Wins Biosimilar Filing Race
Source: Pharmaceutical Technology,
Click here