AAPS Open editor-in-chief coauthored and presented research on using a computer program in a new way.
T he computer program ASAPprime has been used successfully for some time to predict the stability of active pharmaceutical ingredients (APIs) in solid-dosage forms. In the recently published AAPS Open article Prediction of the changes in drug dissolution from an immediate-release tablet containing two active pharmaceutical ingredients using an accelerated stability assessment program (ASAPprime®), the authors demonstrated that the ASAPprime program can also be used to predict the slow-down in dissolution of two APIs in an immediate-release tablet.
“Most, if not all, accelerated stability studies involve the collection of data obtained by exposing the sample to some kind of ‘stressed’ condition and then extrapolating the data to predict the expiration date at the intended storage condition,” explained Christopher M. Riley, Ph.D., coauthor of this paper and editor-in-chief of AAPS Open.
“Traditional stability studies are often time consuming, particularly if more than one factor is involved, and always introduce some degree of uncertainty arising from the errors in the measurements. Ken Waterman and others have demonstrated that errors due to extrapolation of data can be minimized by the application of isoconversion kinetics to give a more reliable prediction of the effects temperature and moisture have on the chemical stability of solid dosage forms. However, this approach has been much less widely used to predict effects of physical instability, such as slow-down in dissolution, on shelf life, and storage conditions. In the study we present in this paper, we were able to show that changes in dissolution of two drugs in a fixed-dose combination tablet seen at high temperature and high relative humidity did not translate to any meaningful changes in product performance under ambient conditions.”
In addition to showing that ASAPprime could be used to model the effects of temperature and relative humidity on dissolution, the software was also used to demonstrate that no special precautions were necessary to protect the tablets from moisture and that they could be stored in Aclar blisters. It was further shown that the water content of the tablet was not a critical quality attribute and need not be included in the drug product specification.
Sharing this research on the next level, Riley presented his team’s findings at the AAPS Workshop on Stability Challenges Not Addressed by Harmonized Guidance, April 3–4 in Rockville, Md. “I believe our approach was well received by the participants,” said Riley. “Rather than simply regurgitating the results from the paper, we challenged the participants to read the paper ahead of time and come to the workshop prepared to discuss our work and offer ideas how the approach could be improved.
“I have been attending scientific conferences and workshops for over 40 years, and I have observed that audience participation has become more and more passive and less and less interactive. The first conference I ever attended as a young graduate student was in 1977 at the Solvay Conference sponsored by the Royal Society of Chemistry in Great Britain on the burgeoning technique of high-performance liquid chromatography. The pioneers of the technique were invited to present their latest unpublished results and the article was provided to the participants ahead of time to prepare their criticisms. The debates were very lively and left a great impression on me as I started my career in pharmaceutical analysis. Nowadays, it may be too much to expect a member of the audience to interrupt a speaker in the middle of a talk and pronounce that ‘you are wrong.’ However, I do believe AAPS leaders have an obligation to provide a forum for healthy debate and more lively discussions, which we encouraged in our session at the stability workshop.”
Do you want to learn more about predicting changes in dissolution through ASAPprime? Read the AAPS Open article, free for download.