Molecular mobility in glassy dispersions

Mehta, Mehak; McKenna, Gregory B.; Suryanarayanan, Raj

doi:10.1063/1.4950768

Cited by 7 publications

(7 citation statements)

References 60 publications

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“…This scenario seems to be even more reliable when we take into account a recent paper by Koperwas et al where it was presented that enhanced dipole–dipole interactions warrant better stability of the supercooled liquid. In this context, it is also worth mentioning the paper by Mehta et al, who studied the crystallization of nifedipine dispersed in various polymers. They also found that strong drug–polymer intermolecular interactions reduce the mobility and enhance physical stability of solid dispersions.…”

Section: Resultsmentioning

confidence: 97%

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Studying the Crystallization of Various Polymorphic Forms of Nifedipine from Binary Mixtures with the Use of Different Experimental Techniques

et al. 2017

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In this paper the crystal growth of nifedipine from pure system and from binary mixtures composed of active substance (API) and two acetylated disaccharides, maltose and sucrose (NIF-acMAL, NIF-acSUC, 5:1 weight ratio), was investigated. Optical snapshots supported by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) measurements showed that mainly β and α forms of nifedipine grow up in all investigated samples. They also revealed that the morphology of growing crystals strongly depends on the presence of modified carbohydrates and temperature conditions. Interestingly, it was found that the activation barrier for the crystal growth of the β polymorph is not affected by acetylated saccharides while the one estimated for the α form changes significantly from 48.5 kJ/mol (pure API) up to 122 kJ/mol (NIF-acMAL system). Moreover, the relationship between the crystal growth rate and structural relaxation times for pure NIF and solid dispersions were analyzed. It turned out that there is a clear decoupling between the crystal growth rate and structural dynamics in both NIF-acMAL and NIF-acSUC binary mixtures. This is in line with recent reports indicating the decoupling phenomenon to be a universal feature of soft matter in the close vicinity of the glass transition temperature.

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Section: Resultsmentioning

confidence: 97%

“…In this context, it is also worth mentioning the paper by Mehta et al, 37 who studied the crystallization of nifedipine dispersed in various polymers. They also found that strong drug−polymer intermolecular interactions reduce the mobility and enhance physical stability of solid dispersions.…”

Section: Molecular Pharmaceuticsmentioning

confidence: 94%

Studying the Crystallization of Various Polymorphic Forms of Nifedipine from Binary Mixtures with the Use of Different Experimental Techniques

et al. 2017

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“…Therefore, predicting the behavior these systems in the glassy state will be of much practical utility. We have the ability to measure the mobility in the glassy state, and this was accomplished in nifedipine–PVP and nifedipine–HPMC systems . It will be interesting to investigate the coupling between mobility and stability below T g and the possible approaches to accomplish this were discussed earlier …”

Section: Resultsmentioning

confidence: 99%

Effect of Polymer Molecular Weight on the Crystallization Behavior of Indomethacin Amorphous Solid Dispersions

Mohapatra

Samanta

Kothari

et al. 2017

Crystal Growth & Design

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The influence of the molecular weight of polyvinylpyrrolidone (PVP) on the molecular mobility and physical stability of indomethacin (IMC)–PVP solid dispersions was investigated over a wide temperature range in the supercooled state. As the polymer molecular weight increased, there was a decrease in molecular mobility as evident from the longer α-relaxation times. Inhibition of IMC crystallization also increased as a function of polymer molecular weight. The extent of H-bonding interaction between drug and polymer, quantified by ssNMR, was independent of polymer molecular weight. Over a polymer concentration range of 5–20% w/w, the temperature dependence of mobility and viscosity was reasonably similar for different grades of PVP. It was concluded that the increase in effectiveness in crystallization inhibition as a function of polymer molecular weight is due to the increased viscosity, which slows down the mobility of these systems.

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“…As another example of such behavior, an interesting study was reported . Here the API, nifedipine, was prepared in amorphous form ( T g = 318 K), along with a 10% w/w solid dispersion with PVPK12 ( T g = 319 K) and HPMCAS ( T g = 320 K).…”

Section: What Do We Know About the Fundamental Aspects Of Isothermal ...mentioning

confidence: 99%

What Are the Important Factors That Influence API Crystallization in Miscible Amorphous API–Excipient Mixtures during Long-Term Storage in the Glassy State?

Newman¹,

Zografi

2021

Mol. Pharmaceutics

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In this Perspective, the authors examine the various factors that should be considered when attempting to use miscible amorphous API–excipient mixtures (amorphous solid dispersions and coamorphous systems) to prevent the solid-state crystallization of API molecules when isothermally stored for long periods of time (a year or more) in the glassy state. After presenting an overview of a variety of studies designed to obtain a better understanding of possible mechanisms by which amorphous API undergo physical instability and by which excipients generally appear to inhibit API crystallization from the amorphous state, we examined 78 studies that reported acceptable physical stability of such systems, stored below T g under “dry” conditions for one year or more. These results were examined more closely in terms of two major contributing factors: the degree to which a reduction in diffusional molecular mobility and API–excipient molecular interactions operates to inhibit crystallization. These two parameters were chosen because the data are readily available in early development to help compare amorphous systems. Since T g – T = 50 K is often used as a rule of thumb for the establishing the minimum value below T g required to reduce diffusional mobility to a period of years, it was interesting to observe that 30 of the 78 studies still produced significant physical stability at values of T g – T < 50 K (3–47 °C), suggesting that factors besides diffusive molecular mobility likely contribute. A closer look at the T g – T < 50 systems shows that hydrogen bonding, proton transfer, disruption of API–API self-associations (such as dimers), and possible π–π stacking were reported for most of the systems. In contrast, five crystallized systems that were monitored for a year or more were also examined. These systems exhibited T g – T values of 9–79, with three of them exhibiting T g – T < 50. For these three samples, none displayed molecular interactions by infrared spectroscopy. A discussion on the impact of relative humidity on long-term crystallization in the glass was included, with attention paid to the relative water vapor sorption by various excipients and effects on diffusive mobility and molecular interactions between API and excipient.

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Molecular mobility in glassy dispersions

Cited by 7 publications

References 60 publications

Studying the Crystallization of Various Polymorphic Forms of Nifedipine from Binary Mixtures with the Use of Different Experimental Techniques

Studying the Crystallization of Various Polymorphic Forms of Nifedipine from Binary Mixtures with the Use of Different Experimental Techniques

Effect of Polymer Molecular Weight on the Crystallization Behavior of Indomethacin Amorphous Solid Dispersions

What Are the Important Factors That Influence API Crystallization in Miscible Amorphous API–Excipient Mixtures during Long-Term Storage in the Glassy State?

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