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Related Concept Videos

Solvents01:12

Solvents

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A solvent is a substance, most often a liquid, that can dissolve other substances. Here, the substance being dissolved is called a solute. When a solvent and a solute combine, they form a solution - a homogenous mixture of both the solvent and the solute. Water is a universal biological solvent. Its polar structure allows it to dissolve many other polar compounds. The ability of water to dissolve is governed by a balance between water molecules binding to each other and binding to the solute.
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Diffusion01:12

Diffusion

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Diffusion is the passive movement of substances down their concentration gradients—requiring no expenditure of cellular energy. Substances, such as molecules or ions, diffuse from an area of high concentration to an area of low concentration in the cytosol or across membranes. Eventually, the concentration will even out, with the substance moving randomly but causing no net change in concentration. Such a state is called dynamic equilibrium, which is essential for maintaining overall...
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Diffusion01:21

Diffusion

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Diffusion is a type of passive transport. In passive transport, a substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across the space. For example, take the diffusion of substances through the air. When someone opens a perfume bottle in a room filled with people, the perfume is at its highest concentration in the bottle and is at its lowest at the edges of the room. The perfume vapor will diffuse, or spread away, from the...
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Pharmaceutical Equivalents01:26

Pharmaceutical Equivalents

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As defined by regulatory standards, pharmaceutical equivalents require generic drug products to have identical dosage forms and chemically identical active pharmaceutical ingredients (APIs). They must adhere to compendial or applicable standards for potency, content uniformity, disintegration times, and dissolution rates. In the case of modified-release dosage forms, variations in drug content are permissible as long as the delivered amount remains consistent with the innovator drug product.
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Titration in Nonaqueous Solvents01:16

Titration in Nonaqueous Solvents

1.4K
Most acid-base titrations are performed in an aqueous medium. In aqueous titrations, water competes with weaker acids or bases for proton donation or acceptance, leading to ambiguous endpoints in the titration curve. Water also affects the partial ionization of weak acids or bases. For example, water accepts a proton from acetic acid to form hydronium and acetate ions. The hydronium ion formed is a stronger acid than acetic acid, and the acetate ion is a stronger base than water. As a result,...
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Ionic Crystal Structures02:42

Ionic Crystal Structures

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Ionic crystals consist of two or more different kinds of ions that usually have different sizes. The packing of these ions into a crystal structure is more complex than the packing of metal atoms that are the same size.
Most monatomic ions behave as charged spheres, and their attraction for ions of opposite charge is the same in every direction. Consequently, stable structures for ionic compounds result (1) when ions of one charge are surrounded by as many ions as possible of the opposite...
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High-Contrast and Fast Photorheological Switching of a Twist-Bend Nematic Liquid Crystal
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Microfluidic droplet liquid reactors for active pharmaceutical ingredient crystallization by diffusion controlled

Robert M Tona1, Thomas A O McDonald, Nima Akhavein

  • 1Advanced Manufacturing Technologies, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. david.x.lai@gsk.com.

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|May 23, 2019
PubMed
Summary
This summary is machine-generated.

A new microfluidic method enables rapid, low-cost screening of active pharmaceutical ingredient (API) crystal forms and habits. This technique controls crystallization by adjusting solvent extraction rates in droplets, impacting crystal size and morphology for better manufacturability.

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Area of Science:

  • Chemical Engineering
  • Materials Science
  • Crystallography

Background:

  • Screening crystal polymorphism and habit is crucial for active pharmaceutical ingredient (API) manufacturability.
  • Traditional methods are often time-consuming and require significant API quantities.

Purpose of the Study:

  • To develop a novel, rapid, and cost-effective method for screening API crystal polymorphism and habit.
  • To demonstrate control over crystallization parameters within microfluidic droplet reactors.

Main Methods:

  • Utilized a microfluidic droplet liquid reactor with a ternary solvent system (solvent, antisolvent, continuous phase).
  • Controlled API crystallization by manipulating solvent extraction rates from droplets into the continuous phase.
  • Investigated the impact of extraction rates on crystal size, habit, and population per droplet.

Main Results:

  • Solvent extraction rate directly influenced API solubility and crystallization outcomes.
  • Slow extraction promoted growth of larger single crystals, while rapid extraction yielded more nuclei.
  • Crystal habit was tunable, with minimal saturation favoring rhombohedral and higher saturation favoring acicular habits.

Conclusions:

  • The microfluidic method offers precise control over crystallization processes.
  • This technique enables rapid identification of favorable crystal morphologies for downstream manufacturing using minimal API.
  • The developed method is effective for screening crystal properties of hydrophobic APIs.