Supersaturating Drug Delivery Systems: The Answer to Solubility-Limited Oral Bioavailability?

Brouwers, Joachim; Brewster, Marcus E.; Augustijns, Patrick

doi:10.1002/jps.21650

Cited by 827 publications

(650 citation statements)

References 95 publications

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“…The success of HPMC as the matrix of amorphous solid dispersions can be attributed to the following reasons: (1) HPMC has a high glass transition temperature around 155°C (HPMC 2910 (Nyamweya and Hoag, 2000)) ensuring appropriate physical as well as chemical stability for the drug at storage temperature (Hancock et al, 1995). (2) The precipitation of the supersaturated drug in the dissolution media can be effectively inhibited with the use of HPMC (Brouwers et al, 2009). For instance, addition of small amount (5%) of HPMC into a surfactant-based formulation of poorly soluble paclitaxel resulted in a 10-fold increase in oral bioavailability in rats due to the precipitation inhibition effect (Gao and Morozowich, 2006).…”

Section: Introductionmentioning

confidence: 99%

AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution

Balogh

Farkas

Verreck

et al. 2016

International Journal of Pharmaceutics

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Section: Introductionmentioning

confidence: 99%

AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution

Balogh

Farkas

Verreck

et al. 2016

International Journal of Pharmaceutics

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“…1) (4). A supersaturation ratio is defined here as the maximum drug concentration over the plateau concentration.…”

Section: Model Development Parameterization Of In Vitro Drug Concentrmentioning

confidence: 99%

“…Precipitation is a function of both concentration and time; the peak concentration and its duration depend on the drug, drug form, dose, and formulation components (the exact dependence of which is the focus of intense current investigation) (5,28,29,(38)(39)(40)(41)(42)(43). If both the peak drug concentration and duration of that peak in vivo were equal to the values determined from the in vitro dissolution profile (Fig.…”

Section: Relationship Between In Vitro Drug Concentration Profile Andmentioning

confidence: 99%

“…Once drug precipitation is complete, drug concentration remains constant. 4 5. There is excess solid drug remaining at the end of absorption.…”

Section: Development Of Mathematical Equations Describing Drug Absorpmentioning

confidence: 99%

“…It is often assumed that the higher the amorphous peak concentration, the higher the bioavailability. However, a higher degree of supersaturation does not always lead to increased absorption, indicating that this parameter alone is not a suitable predictor of bioavailability for potential amorphous formulation (4,5).…”

Section: Introductionmentioning

confidence: 99%

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Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Kleppe

Forney-Stevens

Haskell

et al. 2015

AAPS J

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Abstract. Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closedform analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort.

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Solubility and Dissolution Considerations for Amorphous Solid Dispersions

Ilevbare¹,

Xu²,

John³

et al. 2015

Pharmaceutical Sciences Encyclopedia

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This chapter presents differences between dispersions, amorphous materials, and crystalline forms, and discusses the impact of excipient selection, especially polymers. It provides guidance for solubility and dissolution testing of amorphous dispersions. Crystalline solids are mostly used in pharmaceutical drug formulations because of their physical and chemical stabilities. Amorphous solids are commonly described as condensed phases that lack the long‐range translational order typical of a crystalline solid, although the molecules may have short‐range order. The success of amorphous solids as a supersaturating dosage form depends on the choice of processing conditions to yield a pure amorphous solid with no or minimal crystallization of the amorphous drug during storage and upon dosing. The use of amorphous solid dispersions has become a well‐known strategy for inhibiting crystallization, as the amorphous solid dispersions can have increased physical stability over neat amorphous material.

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Supersaturating Drug Delivery Systems: The Answer to Solubility-Limited Oral Bioavailability?

Cited by 827 publications

References 95 publications

AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution

AC and DC electrospinning of hydroxypropylmethylcellulose with polyethylene oxides as secondary polymer for improved drug dissolution

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Solubility and Dissolution Considerations for Amorphous Solid Dispersions

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