These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Theoretical evaluation of supersaturation of amorphous solid dispersion formulations with different drug/polymer combinations using mathematical modeling.
    Author: Hirai D, Tsunematsu H, Kimura SI, Itai S, Fukami T, Iwao Y.
    Journal: Int J Pharm; 2022 Sep 25; 625():122110. PubMed ID: 35970282.
    Abstract:
    Amorphous solid dispersion (ASD) is a preparation widely used for improving the solubility and low oral absorbability of poorly water-soluble drugs, but the quantitative analysis of its dissolution profiles and its supersaturation status remains an important issue. We previously reported a new mathematical model for analyzing the dissolution characteristics of ASD preparations that enabled evaluation of theoretical solubility of ASDs and crystal precipitation rate constants of ASD preparations. In this study, to analyze the relationship between the mathematical parameters of the model and the dissolution behavior in detail, we simulated the dissolution behaviors upon changing parameters. We quantitatively evaluated the supersaturation of ASD preparations composed of various combinations of two drugs (ibuprofen or indomethacin) and three polymers (polyvinylpyrrolidone (PVP), copovidone or hydroxypropylmethylcellulose (HPMC)). Based on parameter comparison, the difference in the peak of drug concentration between IB/PVP and IB/HPMC ASDs was found to be derived from precipitation rate constant, not the theoretical solubility. In addition, although IMC/PVP ASD had higher solubility than IMC/HPMC ASDs, HPMC could suppress crystal precipitation and maintain supersaturation at higher concentrations than IMC/PVP ASD by comparing parameters derived from model fitting. Thus, our results show that the use of mathematical parameters can illuminate theoretical mechanical information regarding dissolution behaviors of various ASDs and permit a visualization of the character of the dissolution process.
    [Abstract] [Full Text] [Related] [New Search]