Aqueous Solubility Enhancement Through Engineering of Binary Solid Composites: Pharmaceutical Applications

Moore, Michael D.; Wildfong, Peter L.D.

doi:10.1007/s12247-009-9053-7

Cited by 51 publications

(44 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As poorly soluble new chemical entities enter drug development pipelines, different approaches for solubility enhancement may be attempted as they are considered for adoption as candidate molecules. Among these, preparation of solid amorphous dispersions has received considerable attention . Solid dispersions are prepared by rapid co‐solidification of an active pharmaceutical ingredient (API) and a carrier excipient (frequently a water soluble polymer), by one of several methods, including spray drying, super‐critical fluid processing, lyophilization, hot‐melt extrusion, and high‐shear co‐trituration .…”

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Vasa

Dalal

Katz

et al. 2014

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Fifteen model drugs were quenched from 3:1 (w/w) mixtures with polyethylene glycol 4000 (PEG4000). The resulting solids were characterized using powder X-ray diffraction (PXRD), analysis of pair distribution function-transformed PXRD data (where appropriate), hot-stage polarized light microscopy, and differential scanning calorimetry (DSC). Drug/polymer dispersion behavior was classified using the data from each technique, independent of the others, and limitations to single-method characterization of PEG-based systems are highlighted. The data from all characterization techniques were collectively used to classify dispersion behavior, which was compared with single-technique characterization. Of the 15 combinations, only six resulted in solids whose dispersion behavior was consistently described using each standalone technique. The other nine were misclassified using at least one standalone technique, mainly because the phase behavior was ambiguously interpreted when only the data from one technique were considered. The data indicated that a suite of complementary techniques provided better classifications of the phase behavior. Of all the quenched solids, only cimetidine was fully dispersed in PEG4000, suggesting that it solidified from a completely miscible mixture of molten drug and polymer that did not phase separate upon cooling. In contrast, ibuprofen and PEG4000 completely recrystallized during preparation, whereas the remaining 13 drugs were partially dispersed in PEG4000 at this composition.

show abstract

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Vasa

Dalal

Katz

et al. 2014

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Aqueous solubility enhancement 1) and its prediction methods 2) are recently reviewed. Yalkowsky and He provided an extensive database of aqueous solubility of chemicals including many pharmaceutically interested compounds.…”

mentioning

confidence: 99%

Solubility of Acetaminophen and Ibuprofen in Binary and Ternary Mixtures of Polyethylene Glycol 600, Ethanol and Water

Soltanpour

Jouyban

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Experimental solubilities of acetaminophen and ibuprofen in polyethylene glycol 600-water, ethanol-polyethylene glycol 600, and polyethylene glycol 600-water-ethanol mixtures at 25°C are reported. The solubilities of drugs in the presence of ethanol and polyethylene glycol 600 were increased. The Jouyban-Acree model was used to fit the solubility data of each drug in the binary mixtures in which the overall mean relative deviations (OMRDs) for acetaminophen and ibuprofen were 2.9% and 4.3%, respectively. The OMRDs for ternary solvent mixtures for acetaminophen and ibuprofen were 16.8% and 22.4%, respectively. Generally, the errors associated with ibuprofen are larger than that of acetaminophen in both binary and ternary solvent mixtures. The solubilities were predicted using previously trained versions of the Jouyban-Acree and log-linear models with the OMRDs of 38.8% and 52.1%, respectively. Density of the mixed solvents in the absence of the solute was measured and used to train the model and then the density of the saturated solutions was predicted using the trained model and the density of the saturated solutions in mono-solvent systems with the OMRD of 3.2%.

show abstract

“…Craig proposed two mechanisms of drug release from solid dispersions in water soluble carriers namely drug-controlled and carrier-controlled dissolution, the predominance depending on the solubility of the drug in the concentrated aqueous carrier layer adjacent to the solid surface ( Figure 1) [9,10]. For drug-controlled systems, the dissolution rate of solid dispersions is affected by the properties of the drug but not by those of the carrier.…”

Section: Introductionmentioning

confidence: 99%

The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers

Duong

Mooter

2016

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity. Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs. Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

show abstract

Aqueous Solubility Enhancement Through Engineering of Binary Solid Composites: Pharmaceutical Applications

Cited by 51 publications

References 75 publications

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Solubility of Acetaminophen and Ibuprofen in Binary and Ternary Mixtures of Polyethylene Glycol 600, Ethanol and Water

The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers

Contact Info

Product

Resources

About