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Related Concept Videos

Colloidal precipitates01:09

Colloidal precipitates

723
The high insolubility of some precipitates can result in an unfavorable relative supersaturation. This can lead to colloidal particles with a large surface-to-mass ratio, where adsorption is promoted. For instance, in the precipitation of silver chloride, silver ions are adsorbed on the surface of the colloidal particles, forming a primary layer. This layer attracts ions of opposite charge (such as nitrate ions), forming a diffuse secondary layer of adsorbed ions. This electric double layer...
723
Precipitation Processes01:12

Precipitation Processes

560
The experimental conditions in a gravimetric analysis should be optimized to maximize the particle size and purity of the obtained precipitate. Ideally, the concentration of the precipitating reagent should be low with effective stirring to maintain low relative supersaturation for the growth of large crystals. In homogeneous precipitation, the precipitant is slowly generated by a chemical reaction in the solution to avoid local reagent excesses. For example, urea decomposes gradually to...
560
Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism

374
Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
374
Factors Influencing Drug Absorption: Pharmaceutical Parameters01:28

Factors Influencing Drug Absorption: Pharmaceutical Parameters

180
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
180
Washing, Drying, and Ignition of Precipitates00:52

Washing, Drying, and Ignition of Precipitates

1.0K
After filtration, the precipitate is washed to remove coprecipitated impurities and any remaining mother liquor. Colloidal precipitates, such as silver chloride, are washed with an electrolyte (such as dilute nitric acid) to prevent the peptization of the precipitate. In the case of slightly soluble precipitates, the wash solution contains a common ion to reduce solubility. Lead sulfate, which is slightly soluble in water, is washed with dilute sulfuric acid. Similarly, wash solutions may be...
1.0K
Precipitate Formation and Particle Size Control01:16

Precipitate Formation and Particle Size Control

906
In precipitation gravimetry, the precipitating agent should react specifically or selectively with the analyte. While a specific reagent reacts with the analyte alone, a selective reagent can react with a limited number of chemical species.
The obtained precipitate should be either a pure substance of known composition or easily converted to one by a simple process, such as ignition or drying. In addition, the precipitate should be insoluble and easily filterable. In general, filterability...
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Densifying Co-Precipitated Amorphous Dispersions to Achieve Improved Bulk Powder Properties.

Derek S Frank1, Ashish Punia2, Mairead Fahy3

  • 1Process Research & Development, Merck & Co., Inc., Rahway, NJ, USA. derek.frank@merck.com.

Pharmaceutical Research
|October 22, 2022
PubMed
Summary

Hot washing amorphous solid dispersions (ASDs) improved powder flow and density without crystallization. This annealing process enhances materials for pharmaceutical processing compared to non-densified powders.

Keywords:
amorphous dispersionannealingco-precipitationco-processed APImicroprecipitated bulk powder

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Area of Science:

  • Pharmaceutical Science
  • Materials Science
  • Chemical Engineering

Background:

  • Amorphous solid dispersions (ASDs) are crucial for improving the solubility and bioavailability of poorly soluble drugs.
  • Co-precipitation using high-shear devices offers controlled precipitation but can yield powders with poor bulk properties.
  • Downstream processing of pharmaceutical powders requires adequate flowability and bulk density.

Purpose of the Study:

  • To investigate annealing co-precipitated amorphous dispersions (cPAD) using heated anti-solvent washes.
  • To enhance the bulk powder properties of cPAD for improved downstream drug product processing.
  • To evaluate the impact of hot wash densification on material properties and dissolution behavior.

Main Methods:

  • Co-precipitation of amorphous dispersions into a pH-modified aqueous anti-solvent.
  • Washing the precipitated dispersions with heated anti-solvent.
  • Assessment of bulk density, flowability, and dissolution profiles.
  • Comparison with non-heated washed cPAD and spray-dried intermediates.

Main Results:

  • Heated anti-solvent washing significantly improved the flowability and bulk density of cPAD.
  • Densification occurred via annealing above the material's wet glass transition temperature (Tg), collapsing the porous structure without inducing crystallization.
  • Alternative low-shear precipitation resulted in crystallinity, whereas hot wash densification maintained an amorphous state.
  • Densified cPAD showed reduced dissolution rates but achieved equivalent drug concentrations to spray-dried materials within 90 minutes.

Conclusions:

  • Hot wash densification is a viable method to improve the bulk properties of co-precipitated amorphous dispersions.
  • This technique addresses the poor flowability and low bulk density issues associated with high-shear precipitation.
  • Densified cPAD offers a promising alternative for pharmaceutical processing compared to non-densified counterparts.