New set of biorelevant media for better prediction of in vivo performance of poorly water-soluble compounds
Jakobsson, Laura (2020-03-10)
New set of biorelevant media for better prediction of in vivo performance of poorly water-soluble compounds
Jakobsson, Laura
(10.03.2020)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2020042722493
https://urn.fi/URN:NBN:fi-fe2020042722493
Tiivistelmä
In the development of new oral drug compounds, poorly water-soluble compounds are a challenge for the pharmaceutical industry. Dissolution tests are performed to evaluate the dissolution properties of the compound and to select a suitable formulation. Dissolution tests in miniaturized scale enable the use of test also in the early phases of the drug development process, when a limited amount of the compound is available. Dissolution tests that predict better the performance of the compound in patient’s body are needed. More precise in vitro dissolution tests would enable shorter times needed for formulation development. In addition, these more precise tests will reduce the number of clinical studies required.
Our aim was to combine two recently developed applications, a new set of biorelevant media and controlled suspension, for the intrinsic dissolution rate (IDR) determination of poorly water-soluble compound in a miniaturized format. This study was performed from the industry aspect, to see whether the combination of the applications would provide a new tool for the development process of new candidates. This combination of two new methods could improve the prediction of compounds in vivo performance by showing, which factors of the dissolution medium are affecting the most the dissolution rate of the compound. These found factors can be further considered in the development process and possibly streamlines e.g. formulation development.
In this study, the IDR of five poorly water-soluble compounds was determined. The IDR of two research compounds from Orion Corporation and three commercial well-characterized compounds were studied in 13 different biorelevant media. Controlled suspension method was used in the studies. The statistical analyses of the IDR results showed that certain factors of the dissolution medium are affecting the dissolution rate of two studied compounds. Even though logical results were obtained, there was also illogical results, and it is concluded that more optimization work will be needed before these new methods can be further utilized in the pharmaceutical industry.
Our aim was to combine two recently developed applications, a new set of biorelevant media and controlled suspension, for the intrinsic dissolution rate (IDR) determination of poorly water-soluble compound in a miniaturized format. This study was performed from the industry aspect, to see whether the combination of the applications would provide a new tool for the development process of new candidates. This combination of two new methods could improve the prediction of compounds in vivo performance by showing, which factors of the dissolution medium are affecting the most the dissolution rate of the compound. These found factors can be further considered in the development process and possibly streamlines e.g. formulation development.
In this study, the IDR of five poorly water-soluble compounds was determined. The IDR of two research compounds from Orion Corporation and three commercial well-characterized compounds were studied in 13 different biorelevant media. Controlled suspension method was used in the studies. The statistical analyses of the IDR results showed that certain factors of the dissolution medium are affecting the dissolution rate of two studied compounds. Even though logical results were obtained, there was also illogical results, and it is concluded that more optimization work will be needed before these new methods can be further utilized in the pharmaceutical industry.