Amorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus®: Drug-Polymer Miscibility and Intermolecular Interactions

Sarpal, Kanika; Munson, Eric J.

doi:10.1016/j.xphs.2020.12.022

Cited by 19 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the miscibility between drug and polymer can also be investigated using the T 1 and T 1ρ relaxation times obtained from 1 H SS-NMR [59,[63][64][65][66][67]. At present, measuring the T g using differential scanning calorimetry (DSC) is the most widely used approach for determining the miscibility of amorphous solids.…”

Section: Solid-state Nuclear Magnetic Resonance (Nmr)mentioning

confidence: 99%

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Wang

Cheng

et al. 2021

Crystals

View full text Add to dashboard Cite

The amorphous form of a drug usually exhibits higher solubility, faster dissolution rate, and improved oral bioavailability in comparison to its crystalline forms. However, the amorphous forms are thermodynamically unstable and tend to transform into a more stable crystalline form, thus losing their advantages. In order to investigate and suppress the crystallization, it is vital to closely monitor the drug solids during the preparation, storage, and application processes. A list of advanced techniques—including optical microscopy, surface grating decay, solid-state nuclear magnetic resonance, broadband dielectric spectroscopy—have been applied to characterize the physicochemical properties of amorphous pharmaceutical solids, to provide in-depth understanding on the crystallization mechanism. This review briefly summarizes these characterization techniques and highlights their recent advances, so as to provide an up-to-date reference to the available tools in the development of amorphous drugs.

show abstract

Section: Solid-state Nuclear Magnetic Resonance (Nmr)mentioning

confidence: 99%

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Wang

Cheng

et al. 2021

Crystals

View full text Add to dashboard Cite

show abstract

“…A difference of

value less than 7 (MPa) 0.5 predicts adequate [ 58 ]. The Flory-Huggins interaction parameter, derived from the melting point depression method, can also be used in molecular interaction studies between two components [ 59 ].…”

Section: Amorphous Drug Loaded Transdermal Systemsmentioning

confidence: 99%

“…Interaction between the coamorphous drug and vehicle needs to be studied. PEG 400 is reported as a vehicle by several researchers [ 46 , 59 ]. The degree of supersaturation may vary in different vehicles.…”

Section: Amorphous Drug Loaded Transdermal Systemsmentioning

confidence: 99%

Amorphization of Drugs for Transdermal Delivery-a Recent Update

et al. 2022

View full text Add to dashboard Cite

Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.

show abstract

“…An inhomogeneous phase of ASDs can restrict physical intimacy and thus affect the formation of drug−polymer interaction. 21,22 Intermolecular interaction formed between drug and polymer directly influenced not only the in vitro dissolution but also the in vivo performance of ASDs. 23−26 Strong drug−polymer interaction guaranteed fast initial drug dissolution rate, as well as relatively high bioavailability.…”

Section: Introductionmentioning

confidence: 99%

“…An inhomogeneous phase of ASDs can restrict physical intimacy and thus affect the formation of drug–polymer interaction. , Intermolecular interaction formed between drug and polymer directly influenced not only the in vitro dissolution but also the in vivo performance of ASDs. − Strong drug–polymer interaction guaranteed fast initial drug dissolution rate, as well as relatively high bioavailability. , Despite the scientific correlation and significance, there are few comprehensively designed studies to elucidate how the phase structure of ASDs impact the formation of drug–polymer interaction and its influence on dissolution mechanism as well as in vivo performance.…”

Section: Introductionmentioning

confidence: 99%

Inhomogeneous Phase Significantly Reduces Oral Bioavailability of Felodipine/PVPVA Amorphous Solid Dispersion

et al. 2022

View full text Add to dashboard Cite

Inhomogeneity is a key factor that significantly influences the dissolution behavior of amorphous solid dispersion (ASD). However, the underlying mechanisms of the effects of inhomogeneous phase on the dissolution characteristics as well as the bioavailability of ASDs are still unclear. In this study, two types of felodipine/PVPVA based ASDs with 30 wt % drug loading but different homogeneity were prepared: homogeneous "30 wt % ASD" prepared by spray drying, as well as inhomogeneous "30 wt % PM" prepared by physically mixing the sprayed dried 70 wt % ASD with PVPVA. We aimed to investigate (1) drug−polymer interaction mechanism and "apparent" interaction strength within the two ASDs and (2) dissolution mechanism as well as in vivo performance of the two ASDs. DSC thermogram revealing a single T g in 30 wt % ASD confirmed its homogeneous phase. 1 H NMR, FT-IR, and DVS studies collectively proved that strong hydrogen bonding interactions formed between felodipine and PVPVA in ASDs. Moreover, homogeneous "30 wt % ASD" has more numbers of interacting drug−polymer pairs, and thus exhibits stronger "apparent" interaction strength comparing with that of inhomogeneous "30 wt % PM". Unexpectedly,in the in vitro dissolution studies, inhomogeneous "30 wt % PM" showed much faster dissolution and also generated drug concentration ∼4.4 times higher than that of homogeneous "30 wt % ASD". However, drug precipitate recrystallized much slower in homogeneous "30 wt % ASD", presumably because much more polymer coprecipitated with amorphous drug in this system, which helps inhibiting drug crystallization. Surprisingly, homogeneous "30 wt % ASD" showed a significantly higher bioavailability in the in vivo pharmacokinetic studies, with the maximum plasma concentrations (C max ) and the area under the curve (AUC) values of about 2.7 and 2.3 times higher than those of inhomogeneous "30 wt % PM". The above findings indicated that the amorphous state of drug precipitate contributes significantly to increase bioavailability of ASDs, while traditional in vitro dissolution studies, for instance, if we only compare the dissolved drug in solution or the capability of an ASD to generate supersaturation, are inadequate to predict in vivo performance of ASDs. In conclusion, the phase behavior of ASDs directly impact the formation of drug−polymer interaction, which controls not only drug supersaturation in solution but also drug crystallization in precipitate, and ultimately affect the in vivo performance of ASDs.

show abstract

Amorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus®: Drug-Polymer Miscibility and Intermolecular Interactions

Cited by 19 publications

References 45 publications

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Amorphization of Drugs for Transdermal Delivery-a Recent Update

Inhomogeneous Phase Significantly Reduces Oral Bioavailability of Felodipine/PVPVA Amorphous Solid Dispersion

Contact Info

Product

Resources

About