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Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

Sun DD, Lee PI - Acta Pharm Sin B (2014)

Bottom Line: Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs.So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability.This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto M5S 3M2, Ontario, Canada.

ABSTRACT
Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

No MeSH data available.


Related in: MedlinePlus

Amorphous drug release mechanism: crosslinked hydrogels vs. water-soluble polymers.
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f0025: Amorphous drug release mechanism: crosslinked hydrogels vs. water-soluble polymers.

Mentions: To further illustrate the above described differences in drug release mechanism, Fig. 5 depicts the evolution of supersaturation of amorphous drugs released from crosslinked hydrogels versus that from water-soluble polymers. When used as immediate-release dosage forms, ASD based on water-soluble polymers tends to produce a highly supersaturated local environment upon dissolution of the polymer carrier, which often results in rapid recrystallization of the dissolved drug, thereby reducing the local drug concentration and the achievable supersaturation level of the solid dispersions. It is therefore not surprising that solid dispersions of poorly water-soluble drugs in water-soluble polymers usually experience rapid drug recrystallization from supersaturated drug solution upon dissolution of the water-soluble polymer carriers. Whereas the ASD in hydrogels avoids a sudden surge of supersaturation in the surrounding dissolution medium through the above described feedback-controlled diffusion mechanism and thus achieving a more sustained level of supersaturation than that based on water-soluble polymers. This further demonstrates the potential comparative advantage of designing an oral ASD dosage form based on crosslinked hydrogels.


Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

Sun DD, Lee PI - Acta Pharm Sin B (2014)

Amorphous drug release mechanism: crosslinked hydrogels vs. water-soluble polymers.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590291&req=5

f0025: Amorphous drug release mechanism: crosslinked hydrogels vs. water-soluble polymers.
Mentions: To further illustrate the above described differences in drug release mechanism, Fig. 5 depicts the evolution of supersaturation of amorphous drugs released from crosslinked hydrogels versus that from water-soluble polymers. When used as immediate-release dosage forms, ASD based on water-soluble polymers tends to produce a highly supersaturated local environment upon dissolution of the polymer carrier, which often results in rapid recrystallization of the dissolved drug, thereby reducing the local drug concentration and the achievable supersaturation level of the solid dispersions. It is therefore not surprising that solid dispersions of poorly water-soluble drugs in water-soluble polymers usually experience rapid drug recrystallization from supersaturated drug solution upon dissolution of the water-soluble polymer carriers. Whereas the ASD in hydrogels avoids a sudden surge of supersaturation in the surrounding dissolution medium through the above described feedback-controlled diffusion mechanism and thus achieving a more sustained level of supersaturation than that based on water-soluble polymers. This further demonstrates the potential comparative advantage of designing an oral ASD dosage form based on crosslinked hydrogels.

Bottom Line: Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs.So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability.This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto M5S 3M2, Ontario, Canada.

ABSTRACT
Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

No MeSH data available.


Related in: MedlinePlus