Characterizing the dissolution profiles of supersaturable salts, cocrystals, and solvates to enhance in vivo oral absorption

Hisada, Nozomi; Takano, Ryusuke; Takata, Noriyuki; Shiraki, Koji; Ueto, Takamitsu; Tanida, Satoshi; Kataoka, Makoto; Yamashita, Shinji

doi:10.1016/j.ejpb.2016.04.004

Cited by 42 publications

(17 citation statements)

References 21 publications

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“…All the PG samples of one manufacturer failed the quality test. This might be due to manufacturing inadequacies [24]; at present, we are still investigating the cause.…”

Section: Quality Analysismentioning

confidence: 98%

Substandard and Falsified Medicines in Myanmar

et al. 2020

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Background: substandard and falsified medicines (SFMs) are a threat to public health. The availability of SFMs in Myanmar was reported by the World Health Organization (WHO) in 1999, but there have been few systematic surveys on falsified medicines in Myanmar since then. The aim of this study is to examine the extent of SFMs for sale in Myanmar. Methods: target medicines were tablets of candesartan, metformin, and pioglitazone, and infusions of ciprofloxacin and levofloxacin. Samples were collected from hospitals, pharmacies, and wholesalers located in the Mandalay region in 2015. We carried out observation testing, authenticity investigation, and quality testing to search for SFMs, and analyzed the relationship between SFMs and the price and store type. Results: There were no falsified medicines found in the authenticity check, though there remained a problem due to low response rates from manufacturers and regulatory authorities. In the quality test, some tablets of metformin and pioglitazone made in India failed the dissolution test. Conclusions: although no serious problems were found, some substandard medicines were detected. Regular surveys to monitor SFMs are therefore recommended, together with further regulatory guidance to improve conditions in all medicine manufacturers, distributors, and pharmacies.

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“…All the PG samples of one manufacturer failed the quality test. This might be due to manufacturing inadequacies [24]; at present, we are still investigating the cause.…”

Section: Quality Analysismentioning

confidence: 98%

Substandard and Falsified Medicines in Myanmar

et al. 2020

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“…Therefore, the cocrystals sustained supersaturation state over several hours in these solutions and the reported solubility is named as dynamic solubility here to discriminate from equilibrium solubility because it is a kinetic result. Sustaining the supersaturation state in these solutions will be advantageous for biological absorption via oral administration 47 . Interestingly, the hydrate was not detected in solubility residue of the TAK-441 anhydrate (supporting information 5) although a hydrate is often thermodynamically preferable in aqueous solution 48 .…”

Section: Aqueous Dissolution and Dynamic Solubility Profilesmentioning

confidence: 99%

Cocrystallization Enhanced TAK-441 Aqueous Solubility and Suppressed High Solvatomorphism

Iwata

Karashima

Ikeda

2016

Crystal Growth & Design

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TAK-441 was cocrystallized to enhance its aqueous solubility and suppress its high solvatomorphism. A TAK-441/L-malic acid (2:1) cocrystal and a TAK-441/L-tartaric acid (2:1) cocrystal were observed and they exhibited isomorphism. These cocrystals were 2-3 times more soluble than its free form in aqueous solutions and directly crystallized without solvate formation in various organic solvents. The cocrystals were chemically and physically stable under stress conditions and are predicted to have sufficient stability to ensure an adequate shelf-life. The results demonstrated that the cocrystals had a more preferable pharmaceutical profile and that cocrystallization can both improve oral bioavailability and simplify crystal form control simultaneously. Abstract.TAK-441 was cocrystallized to enhance its aqueous solubility and suppress its high solvatomorphism. A TAK-441/L-malic acid (2:1) cocrystal and a TAK-441/L-tartaric acid (2:1) cocrystal were observed and they exhibited isomorphism. These cocrystals were 2-3 times more soluble than its free form in aqueous solutions and directly crystallized without solvate formation in various organic solvents. The cocrystals were chemically and physically stable under stress conditions and are predicted to have sufficient stability to ensure an adequate shelf-life. The results demonstrated that the cocrystals had a more preferable pharmaceutical profile and that cocrystallization can both improve oral bioavailability and simplify crystal form control simultaneously.Introduction.

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“…The degree of supersaturation and its transformation rate to less soluble forms are determining the in vivo performance of supersaturable systems. 52 Furthermore, in vivo occurrence of supersaturation, precipitation, and re-dissolution of precipitate are largely dependent on physiological conditions of GI such as pH, transit time, and food effect. 53 , 54 …”

Section: Effects Of Supersaturation/precipitation On Cocrystals In VImentioning

confidence: 99%

“…Box 1 summarizes important characteristics to be evaluated in the design of supersaturable cocrystals to efficiently improve oral absorption. 52 , 55 Ability to generate and maintain a high degree of supersaturation for sufficient period of time in vivo is the most important property. The drug plasma exposure may be significantly increased if a sustained level of supersaturated concentration has to be maintained in the GI tract for the time scale that is sufficient for absorption to take place.…”

Section: Effects Of Supersaturation/precipitation On Cocrystals In VImentioning

confidence: 99%

Recent advances in improving oral drug bioavailability by cocrystals

et al. 2018

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Introduction: Oral drug delivery is the most favored route of drug administration. However, poor oral bioavailability is one of the leading reasons for insufficient clinical efficacy. Improving oral absorption of drugs with low water solubility and/or low intestinal membrane permeability is an active field of research. Cocrystallization of drugs with appropriate coformers is a promising approach for enhancing oral bioavailability. Methods: In the present review, we have focused on recent advances that have been made in improving oral absorption through cocrystallization. The covered areas include supersaturation and its importance on oral absorption of cocrystals, permeability of cocrystals through membranes, drug-coformer pharmacokinetic (PK) interactions, conducting in vivo-in vitro correlations for cocrystals. Additionally, a discussion has been made on the integration of nanocrystal technology with supramolecular design. Marketed cocrystal products and PK studies in human subjects are also reported. Results: Considering supersaturation and consequent precipitation properties is necessary when evaluating dissolution and bioavailability of cocrystals. Appropriate excipients should be included to control precipitation kinetics and to capture solubility advantage of cocrystals. Beside to solubility, cocrystals may modify membrane permeability of drugs. Therefore, cocrystals can find applications in improving oral bioavailability of poorly permeable drugs. It has been shown that cocrystals may interrupt cellular integrity of cellular monolayers which can raise toxicity concerns. Some of coformers may interact with intestinal absorption of drugs through changing intestinal blood flow, metabolism and inhibiting efflux pumps. Therefore, caution should be taken into account when conducting bioavailability studies. Nanosized cocrystals have shown a high potential towards improving absorption of poorly soluble drugs. Conclusions: Cocrystals have found their way from the proof-of-principle stage to the clinic. Up to now, at least two cocrystal products have gained approval from regulatory bodies. However, there are remaining challenges on safety, predicting in vivo behavior and revealing real potential of cocrystals in the human.

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Characterizing the dissolution profiles of supersaturable salts, cocrystals, and solvates to enhance in vivo oral absorption

Cited by 42 publications

References 21 publications

Substandard and Falsified Medicines in Myanmar

Substandard and Falsified Medicines in Myanmar

Cocrystallization Enhanced TAK-441 Aqueous Solubility and Suppressed High Solvatomorphism

Recent advances in improving oral drug bioavailability by cocrystals

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