An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD)

Shah, Kosha B; Patel, Piyush; Khairuzzaman, Akm; Bellantone, Robert A.

doi:10.1016/j.ijpharm.2014.04.012

Cited by 23 publications

(7 citation statements)

References 20 publications

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“…26 These measurements can be carried out in relatively simple side-by-side diffusion cells or use more complex pulsatile microdialysis methods. 9 Phase Transitions During Non-Sink Dissolution Testing Two phase transitions are possible during dissolution, crystallization, or LLPS (which may be followed by crystallization). LLPS can only be observed if the dissolution conditions and formulation factors are such that the amorphous solubility can be exceeded on dissolution of the formulation.…”

Section: Determination Of Supersaturationmentioning

confidence: 99%

“…Advanced in vitro dissolution techniques have contributed to the real-time quantification of drug concentrations in a supersaturated state without the interference of undissolved or newly formed nano-sized particulates. [7][8][9][10] Thus, dissolution methods under non-sink conditions have become an increasingly important strategy in measuring the true performance of supersaturating formulations and drug products by assessing the extent of supersaturation that is generated as well as the associated crystal nucleation and growth kinetics. For this reason, concentrationetime profiles generated from supersaturated drug delivery systems under non-sink conditions are generally recognized as a direct evaluation of their ability to achieve and maintain drug supersaturation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems

Sun

Wen

Taylor

2016

Journal of Pharmaceutical Sciences

117

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With recent advances in the development of supersaturating oral dosage forms for poorly water-soluble drugs, pharmaceutical scientists are increasingly applying in vitro dissolution testing under non-sink conditions for a direct evaluation of their ability to generate and maintain supersaturation as a predictive surrogate for ensuring product quality and in vivo performance. However, the scientific rationale for developing the appropriate non-sink dissolution methodologies has not been extensively debated. This calls for a comprehensive discussion of recent research efforts on theoretical and experimental considerations of amorphous solubility, liquid-liquid phase separation, and phase transitions of drugs in a supersaturated solution when dissolution testing is performed under supersaturated non-sink conditions. In addition, we outline the concept of "sink index" that quantifies the magnitude of deviations from perfect sink dissolution conditions in the sink/non-sink continuum and some considerations of non-sink dissolution testing for marketed drug products. These factors should be carefully considered in recommending an adequately discriminatory dissolution method in the performance assessment of supersaturating drug delivery systems.

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Section: Determination Of Supersaturationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems

Sun

Wen

Taylor

2016

Journal of Pharmaceutical Sciences

117

View full text Add to dashboard Cite

show abstract

“…For example, in traditional dissolution testing, an aliquot is removed from the sample solution; the solution is filtered, placed in an organic phase, and then measured for drug concentration. However, for a drug product that is comprised of nanoparticles, the particles may pass through the filter pores, and dissolve into the molecular constituents when preparing the solution for bioanalysis (Figure a). Thus, the typical testing method would produce a higher value of free drug content than is actually present in the solution.…”

Section: Process Development Considerations For Drug Products Containmentioning

confidence: 99%

Product quality for nanomaterials: current U.S. experience and perspective

Tyner

Zou

Yang

et al. 2015

WIREs Nanomed Nanobiotechnol

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In recent years, there has been an increased focus on developing novel drug delivery systems and targeted therapies through the use of nanotechnology and nanomaterials. Such focus is translating to an increasing number of investigational new drug (IND) applications, new drug applications (NDAs), and abbreviated new drug applications (ANDAs) for drug products containing nanomaterials to the United States Food and Drug Administration (FDA). Although subject to the same rigorous regulatory standards and regulatory pathways as any drug product, unique properties that arise from the small size, large surface area, and polydispersity of nanomaterials may lead to additional scientific considerations when following current FDA guidelines and practices for drug evaluation. This review article will discuss these scientific considerations based on the experience with FDA-approved drug products containing nanomaterials.

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“…The most widely recognized practice for the solubility assurance detailed depended on the separation by filtration to isolate non-dissolved nanoparticles from the solution utilizing the membrane filters of different pore sizes (0.1, 0.22, and 0.45m pore size) [18][19][20]. A couple of reports have likewise demonstrated the utilization of molecular weight cut-off filters [21], dialysis bag method [22], centrifugation [23], and ultracentrifugation [24] for the separation of non-dissolved and dissolved nanocrystals while estimating solubility. Although, proof of adequate separation of non-dissolved and dissolved nanocrystals has been unclear.…”

Section: Introductionmentioning

confidence: 99%

A a Review on the Role of Nanocrystals and Nanosuspensions in Drug Delivery Systems

et al. 2019

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Nearly 40% of drugs coming to the market nowadays are having poor solvency related issues and 70% molecules in the discovery pipeline are in effect fundamentally insoluble in water. Nanocrystals is an unmistakable instrument to tackle the issue identified with poor fluid solvency and helps in improving the bioavailability of various drugs as presented in the literature. The particle size reduction came about into the temperamental nanocrystalline system and the phenomenon of ostawald ripening happens. These techniques are preparing to the improvement of nanosized objects, which can play out multiple technological tasks. There are a few couples of noteworthy benefits of nanocrystal formulations, for example, upgrade oral bioavailability, improved dose proportionality, reduced food effects, appropriateness for administration by all routes and probability of sterile filtration because of diminished particle size range. One of the most adequate preferences of nanocrystals is their wide scope of utilization, for example, ophthalmic delivery, oral delivery, transdermal delivery, pulmonary delivery, intravenous delivery and targeted delivery, especially for tumour and brain. The increment in the commercial value of nanocrystals just as the measure of nanocrystal products in the market is picking up more of attention to be utilized as a strategy so as to get commercial advantages. In this paper, a brief and accurate precis of nanosuspension is stated with a specific spotlight on nanosuspension preparation methodologies, benefits and few major applications of nanosuspensions. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s

show abstract

An improved method for the characterization of supersaturation and precipitation of poorly soluble drugs using pulsatile microdialysis (PMD)

Cited by 23 publications

References 20 publications

Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems

Non-Sink Dissolution Conditions for Predicting Product Quality and In Vivo Performance of Supersaturating Drug Delivery Systems

Product quality for nanomaterials: current U.S. experience and perspective

A a Review on the Role of Nanocrystals and Nanosuspensions in Drug Delivery Systems

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