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Fundamental aspects of solid dispersion technology for poorly soluble drugs.

Huang Y, Dai WG - Acta Pharm Sin B (2013)

Bottom Line: The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance.In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

ABSTRACT
The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

No MeSH data available.


Related in: MedlinePlus

The predicted χ–T relationship (Eq. (4)) for the felodipine/poly(acrylic acid) and fenbufen–poly(vinyl pyrrolidone) drug polymer systems. The original melting point depression data used in the calculation are taken from Refs. 14 and 33.
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f0025: The predicted χ–T relationship (Eq. (4)) for the felodipine/poly(acrylic acid) and fenbufen–poly(vinyl pyrrolidone) drug polymer systems. The original melting point depression data used in the calculation are taken from Refs. 14 and 33.

Mentions: As shown by Lin and Huang14, the χ–T relationship allows the whole phase diagram for a drug–polymer solid dispersion to be constructed including both the drug solubility temperature curve and the amorphous phase separation curve. As illustrated in detail by Lin and Huang14, the χ–T relationship is obtained (Fig. 5) by fitting experimental melting point depression data (Tm~ϕ) to the following equation which is based on the Flory–Huggins theory (Eq. (5))30–32.(5)ΔHm0R(1Tm0−1Tm)=lnϕ+(1−1m)(1−ϕ)+χTm(1−ϕ)2Here ∆Hm0 is the enthalpy of melting of pure drug crystals, R is the ideal gas constant, Tm0 and Tm are the melting points of the pure drug crystals and drug crystals in the solid dispersion with drug volume faction of ϕ. Please note that the drug–polymer interaction parameter χ is temperature dependent and the value in Eq. (5) is that at the temperature Tm. When using Eq. (5), χ is usually assumed to be constant and, because the experimentally available Tm range is narrow, this assumption holds true and melting point depression data can give a good fit to Eq. (5). However, when Eq. (5) is used to estimate drug solubility at low temperatures such as at the storage temperature, the χ–T variation cannot be neglected (Fig. 5)33 without overestimating drug solubility.


Fundamental aspects of solid dispersion technology for poorly soluble drugs.

Huang Y, Dai WG - Acta Pharm Sin B (2013)

The predicted χ–T relationship (Eq. (4)) for the felodipine/poly(acrylic acid) and fenbufen–poly(vinyl pyrrolidone) drug polymer systems. The original melting point depression data used in the calculation are taken from Refs. 14 and 33.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590721&req=5

f0025: The predicted χ–T relationship (Eq. (4)) for the felodipine/poly(acrylic acid) and fenbufen–poly(vinyl pyrrolidone) drug polymer systems. The original melting point depression data used in the calculation are taken from Refs. 14 and 33.
Mentions: As shown by Lin and Huang14, the χ–T relationship allows the whole phase diagram for a drug–polymer solid dispersion to be constructed including both the drug solubility temperature curve and the amorphous phase separation curve. As illustrated in detail by Lin and Huang14, the χ–T relationship is obtained (Fig. 5) by fitting experimental melting point depression data (Tm~ϕ) to the following equation which is based on the Flory–Huggins theory (Eq. (5))30–32.(5)ΔHm0R(1Tm0−1Tm)=lnϕ+(1−1m)(1−ϕ)+χTm(1−ϕ)2Here ∆Hm0 is the enthalpy of melting of pure drug crystals, R is the ideal gas constant, Tm0 and Tm are the melting points of the pure drug crystals and drug crystals in the solid dispersion with drug volume faction of ϕ. Please note that the drug–polymer interaction parameter χ is temperature dependent and the value in Eq. (5) is that at the temperature Tm. When using Eq. (5), χ is usually assumed to be constant and, because the experimentally available Tm range is narrow, this assumption holds true and melting point depression data can give a good fit to Eq. (5). However, when Eq. (5) is used to estimate drug solubility at low temperatures such as at the storage temperature, the χ–T variation cannot be neglected (Fig. 5)33 without overestimating drug solubility.

Bottom Line: The solid dispersion has become an established solubilization technology for poorly water soluble drugs.Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance.In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

ABSTRACT
The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug-polymer two-component system, the drug-polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

No MeSH data available.


Related in: MedlinePlus