Structure and energetics of intermolecular association in two lurasidone co-amorphous drug systems

2021 ◽  
pp. 130709
Author(s):  
Joana F.C. Silva ◽  
Mário T.S. Rosado ◽  
M. Ermelinda S. Eusébio
2017 ◽  
Vol 23 (3) ◽  
pp. 350-361 ◽  
Author(s):  
Hisham Al-Obaidi ◽  
Mridul Majumder ◽  
Fiza Bari

Crystalline and amorphous dispersions have been the focus of academic and industrial research due to their potential role in formulating poorly water-soluble drugs. This review looks at the progress made starting with crystalline carriers in the form of eutectics moving towards more complex crystalline mixtures. It also covers using glassy polymers to maintain the drug as amorphous exhibiting higher energy and entropy. However, the amorphous form tends to recrystallize on storage, which limits the benefits of this approach. Specific interactions between the drug and the polymer may retard this spontaneous conversion of the amorphous drug. Some studies have shown that it is possible to maintain the drug in the amorphous form for extended periods of time. For the drug and the polymer to form a stable mixture they have to be miscible on a molecular basis. Another form of solid dispersions is pharmaceutical co-crystals, for which research has focused on understanding the chemistry, crystal engineering and physico-chemical properties. USFDA has issued a guidance in April 2013 suggesting that the co-crystals as a pharmaceutical product may be a reality; but just not yet! While some of the research is still oriented towards application of these carriers, understanding the mechanism by which drug-carrier miscibility occurs is also covered. Within this context is the use of thermodynamic models such as Flory-Huggins model with some examples of studies used to predict miscibility.


2020 ◽  
Vol 16 (5) ◽  
pp. 529-538
Author(s):  
Gregory K. Webster ◽  
Cynthia A. Pommerening ◽  
Whitney W. Harman ◽  
Mathew A. Gragg ◽  
Jian-Hwa Han ◽  
...  

Background: Enabling formulations have been implemented by the pharmaceutical industry as an effective tool for keeping Active Pharmaceutical Ingredient (API) in an amorphous state. Upon dosing in the amorphous state, many drugs which fail to demonstrate bioactivity due to the limited solubility and bioavailability of their crystalline form become bioavailable. Purpose: The analytical techniques use today for crystallinity detection are challenged by the sensitivity and robustness needed to achieve a 5% quantitation limit in low dose drug products. Our laboratory has developed a novel procedure capable of meeting this sensitivity and selectivity requirement. This is achieved by exploiting the differences in kinetic solubility of the formulated amorphous and free crystalline forms of API currently being used in dosage form platforms. Methods: Representative amorphous drug formulations were prepared and spiked with varying levels of crystalline drug substances to evaluate the selectivity and recovery of the crystalline drug substance from the product formulation. Kinetic solubility testing using a (i) Particle wetting phase, (ii) Particle suspending/erosion phase, (iii) Sampling time point and (iv) A total recovery determination for the drug substance. Results: The method selectively and quantitatively distinguishes crystalline drug substance from amorphous drug substance for samples spiked from 2.5% to 10% of the nominal label concentration of the API in the dosage form matrix. Conclusion: The kinetic solubility approach reported here achieves sensitive crystallinity quantitation for low drug level amorphous drug formulations at levels not yet achieved by complimentary analytical techniques.


2001 ◽  
Vol 276 (50) ◽  
pp. 47671-47674 ◽  
Author(s):  
Yi-Chien Lin ◽  
Jing-Wen Shih ◽  
Chia-Ling Hsu ◽  
Jing-Jer Lin

The protein Cdc13p binds telomeresin vivoand is essential for the maintenance of the telomeres ofSaccharomyces cerevisiae. In addition, Cdc13p is known to bind single-stranded TG1–3DNAin vitro. Here we have shown that Cdc13p also binds DNA quadruplex, G-quartet, formed by TG1–3DNA. Moreover, the binding of Cdc13p causes a partial denaturing of the G-quartet DNA. Formation of DNA quadruplexes may involve the intermolecular association of TG1–3DNA and inhibit the extension of telomeres by telomerase. Thus, our finding suggests that Cdc13p may disrupt telomere association and facilitate telomere replication.


Langmuir ◽  
2007 ◽  
Vol 23 (19) ◽  
pp. 9866-9874 ◽  
Author(s):  
Lennart Lindfors ◽  
Pia Skantze ◽  
Urban Skantze ◽  
Jan Westergren ◽  
Ulf Olsson

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