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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.


Three possible scenarios of drug dispersion from solid dispersions. (A) Particles dissolve rapidly and release drug into a highly supersaturated solution; subsequently drug precipitates as amorphous and/or crystalline particles onto which polymer adsorbs as a stabilizer; (B) drug and polymer are gradually released while drug remains amorphous in the undissolved particles; and (C) drug and polymer are gradually released but drug is present as crystals in the undissolved particles especially near their surfaces. The free drug concentration is dependent on the solubility of either amorphous or crystalline drug which in turn depends on the drug/polymer ratio, polymer dissolution rate and drug crystallization rate.
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f0030: Three possible scenarios of drug dispersion from solid dispersions. (A) Particles dissolve rapidly and release drug into a highly supersaturated solution; subsequently drug precipitates as amorphous and/or crystalline particles onto which polymer adsorbs as a stabilizer; (B) drug and polymer are gradually released while drug remains amorphous in the undissolved particles; and (C) drug and polymer are gradually released but drug is present as crystals in the undissolved particles especially near their surfaces. The free drug concentration is dependent on the solubility of either amorphous or crystalline drug which in turn depends on the drug/polymer ratio, polymer dissolution rate and drug crystallization rate.

Mentions: Depending on the type of solid dispersion, dissolution can occur in three possible ways (Fig. 6). When the drug loading is low, the drug and polymer in the solid dispersion dissolve rapidly (Fig. 6A) after which drug is continuously absorbed and can undergo precipitation in the presence of polymer and endogenous compounds such as bile acids, phospholipids and mucin. As described in detailed by Friesen et al.9, various structures may form including free drug (the major species, if not the only species, being absorbed, so its concentration is what matters for absorption), drugs in bile salt/phospholipid micelles, amorphous drug nanoprecipitates with polymers, and possibly drug nanocrystals stabilized with polymers, all of which are in dynamic exchange with each other. Since such nanoparticles can escape filtration or centrifugation, the apparent solubility of a drug can be erroneously high. Nevertheless, with the proper choice of polymers, the free drug concentration can be maintained at the solubility of amorphous drugs9,35. However, it should be noted that, in theory, the highest concentration of free drug in the dissolution media is even higher, corresponding to the spinodal amorphous phase separation line, above which the drug forms amorphous aggregates spontaneously36.


Fundamental aspects of solid dispersion technology for poorly soluble drugs.

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

Three possible scenarios of drug dispersion from solid dispersions. (A) Particles dissolve rapidly and release drug into a highly supersaturated solution; subsequently drug precipitates as amorphous and/or crystalline particles onto which polymer adsorbs as a stabilizer; (B) drug and polymer are gradually released while drug remains amorphous in the undissolved particles; and (C) drug and polymer are gradually released but drug is present as crystals in the undissolved particles especially near their surfaces. The free drug concentration is dependent on the solubility of either amorphous or crystalline drug which in turn depends on the drug/polymer ratio, polymer dissolution rate and drug crystallization rate.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0030: Three possible scenarios of drug dispersion from solid dispersions. (A) Particles dissolve rapidly and release drug into a highly supersaturated solution; subsequently drug precipitates as amorphous and/or crystalline particles onto which polymer adsorbs as a stabilizer; (B) drug and polymer are gradually released while drug remains amorphous in the undissolved particles; and (C) drug and polymer are gradually released but drug is present as crystals in the undissolved particles especially near their surfaces. The free drug concentration is dependent on the solubility of either amorphous or crystalline drug which in turn depends on the drug/polymer ratio, polymer dissolution rate and drug crystallization rate.
Mentions: Depending on the type of solid dispersion, dissolution can occur in three possible ways (Fig. 6). When the drug loading is low, the drug and polymer in the solid dispersion dissolve rapidly (Fig. 6A) after which drug is continuously absorbed and can undergo precipitation in the presence of polymer and endogenous compounds such as bile acids, phospholipids and mucin. As described in detailed by Friesen et al.9, various structures may form including free drug (the major species, if not the only species, being absorbed, so its concentration is what matters for absorption), drugs in bile salt/phospholipid micelles, amorphous drug nanoprecipitates with polymers, and possibly drug nanocrystals stabilized with polymers, all of which are in dynamic exchange with each other. Since such nanoparticles can escape filtration or centrifugation, the apparent solubility of a drug can be erroneously high. Nevertheless, with the proper choice of polymers, the free drug concentration can be maintained at the solubility of amorphous drugs9,35. However, it should be noted that, in theory, the highest concentration of free drug in the dissolution media is even higher, corresponding to the spinodal amorphous phase separation line, above which the drug forms amorphous aggregates spontaneously36.

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.