Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method and Comparison of Solubilities of Indomethacin and Nifedipine in PVP, PVP/VA, and PVAc

Sun, Ye; Tao, Jing; Zhang, Geoff G. Z.; Yu, Lian

doi:10.1002/jps.22251

Cited by 215 publications

(248 citation statements)

References 11 publications

Supporting

Mentioning

234

Contrasting

Order By: Relevance

“…Utilization of solid dispersions instead of physical mixtures in the evaluation of drug-polymer solubility is one of the features that distinguishes this method from other commonly used, based on melting point depression [18,17]. However, the applicability of this approach depends strongly on the type of a solid dispersion which must reveal an amorphous and supersaturated character and good miscibility between components at the molecular level.…”

Section: Physicochemical Analysis Of Tadalafil Solid Dispersionsmentioning

confidence: 99%

“…4). Thus, thermal degradation of Td and PVP-VA, even at a heating rate of 10 °C/min, prevents the use of conventional methods for solubility assessment, which requires reliable measurements of the melting events of the drug [13,18,17]. …”

Section: Physicochemical Analysis Of Tadalafil Solid Dispersionsmentioning

confidence: 99%

“…While conventional methods employed to determine solubility of drugs in polymer typically use slow heating rates [18,17] to attain solubility equilibrium as close as practically achievable, this is not always possible especially when the drug (or polymer) is known to thermally decompose. On the other hand, by applying fast heating rates decomposition upon/after melting can be diminished or eliminated [14].…”

Section: Modified Melting Point Depression -Hsdscmentioning

confidence: 99%

“…Apart from thermal degradation, the biggest drawback of this method is the risk of solubility underestimation caused by low molecular mobility in a viscous polymer and an inadequate shift of the endotherm. Modifications involving initial milling of physical mixtures, annealing and different heating rates improve the protocol but significantly extend the analysis [18,17].…”

Section: Introductionmentioning

confidence: 99%

“…The duration of the annealing step was optimized to allow the drug to dissolve in the amorphous polymer, similar to the treatment used by Sun et al [17]. Solid dispersions of Td in PVP-VA (Td/PVP-VA) in this investigation were produced by spray-drying.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Wlodarski

Sawicki

Kozyra

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

The aim of this paper was to evaluate physical stability of solid dispersions in respect to the drug, tadalafil (Td), in vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA). Nine solid dispersions of Td in PVP-VA (Td/PVP-VA) varied in terms of quantitative composition (1:9-9:1, w/w) were successfully produced by spray-drying. Their amorphous nature, supersaturated character and molecular level of mixing (a solid solution structure) were subsequently confirmed using DSC, PXRD, SEM and calculation of Hansen total solubility parameters. Due to thermal degradation of both components before the melting point of Td

show abstract

Section: Physicochemical Analysis Of Tadalafil Solid Dispersionsmentioning

confidence: 99%

Section: Physicochemical Analysis Of Tadalafil Solid Dispersionsmentioning

confidence: 99%

Section: Modified Melting Point Depression -Hsdscmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Wlodarski

Sawicki

Kozyra

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

show abstract

Translational Pharmaceutics and Early Phase Clinical Development

Bhattachar

Tan

Stamatis

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Translational pharmaceutics is a relatively new cross‐disciplinary construct that integrates discovery and development for efficiently enabling discovery activities to deliver commercially viable medicines. This article describes the role and deliverables of its various subfunctions, namely, preclinical formulations, physical chemistry, drug product prototyping and development, and biopharmaceutics. The integrated aspects of these deliverables, that enable drug discovery, while also influencing and enabling the selection of compounds for clinical testing, in a manner that embraces the principles of R&D essentialism and design thinking, are also described. This article also illustrates how cost and time savings can be achieved through the application of robust mathematical modeling where possible, to guide the generation of the most relevant experimental data, followed by risk‐based decision‐making to inform commercial product design. Although the article is mostly focused on traditional small molecules, the principles described here can be adapted to include other types of molecular and biologic entities, including the newer molecular modalities that are rapidly gaining importance in the industry.

show abstract

Amorphous Solid Dispersion Screening

Newman¹

2015

Pharmaceutical Sciences Encyclopedia

View full text Add to dashboard Cite

Finding the optimal form for drug development can involve a number of different screening activities, including a search for polymorphs, salts, cocrystals, and/or amorphous solid dispersions. High‐risk compounds will require special formulations that include amorphous solid dispersions. An amorphous dispersion screen is performed to find a suitable amorphous dispersion that exhibits acceptable properties. The screening performed in early development may focus on parameters such as solubility, supersaturation, short‐term physical and chemical stability, and animal bioavailability to get into early‐phase clinical trials quickly and establish proof of concept. Before starting an amorphous dispersion screen project, information on the active pharmaceutical ingredient (API) is needed. This may include chemical structure, solid form, physical stability, chemical stability, log P, hydrogen bond donors/acceptors, calculated solubility parameters, and known solubilities of the solid in various solvents/biorelevant media.

show abstract

Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method and Comparison of Solubilities of Indomethacin and Nifedipine in PVP, PVP/VA, and PVAc

Cited by 215 publications

References 11 publications

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Translational Pharmaceutics and Early Phase Clinical Development

Amorphous Solid Dispersion Screening

Contact Info

Product

Resources

About