OIA1011 CRYSTALLINE VS. AMORPHOUS SOLIDS & SOLUBILITY

What are the two main types of solid phases?

Crystalline and amorphous

Define crystalline solids.

Solids with particles arranged in a regular, repeating lattice structure

Define amorphous solids

Solids with no long-range molecular order, leading to a more random particle arrangement

Why is solubility important in pharmaceutics?

Poor solubility leads to poor absorption, reduced bioavailability, and increased drug development costs

What are unit cells?

The smallest repeating structure in a crystal lattice

Name the most common types of unit cells in pharmaceutics.

Triclinic, monoclinic, and orthorhombic

What are the characteristics of crystalline solids?

Thermodynamically stable, sharp melting points, and low solubility

Provide an example of a crystalline solid used in pharmaceuticals.

Sodium chloride

What is the glass transition temperature (Tg)?

The temperature at which an amorphous solid transitions from a brittle state to a rubbery state

Why are amorphous solids often used in drug formulations?

They exhibit higher solubility, faster dissolution rates, and improved bioavailability

What are common examples of amorphous materials?

Glass, rubber, and certain polymers

What is polymorphism?

The ability of a solid to exist in more than one crystalline form with different physical and chemical properties

Provide an example of a drug affected by polymorphism.

Ritonavir, where polymorphic changes caused solubility and bioavailability issues

How does polymorphism affect drug properties?

It influences solubility, stability, melting point, and bioavailability

What is the significance of Form I and Form II in polymorphism?

Form I is typically the most stable, while Form II may exhibit higher solubility but lower stability

How do crystalline and amorphous solids differ in stability?

Crystalline solids are more thermodynamically stable, while amorphous solids are less stable and prone to crystallization

Compare the solubility of crystalline and amorphous solids.

Amorphous solids generally have higher solubility than crystalline solids

Which solid type is preferred for drugs with poor water solubility?

Amorphous forms are preferred to enhance bioavailability

What is a disadvantage of using amorphous solids in formulations?

They are less stable and may revert to crystalline forms over time

How does the solubility of a drug affect its bioavailability?

Higher solubility improves absorption and bioavailability

What is the impact of poor solubility during drug development?

It can lead to rejection in clinical trials, increasing costs and development time

Why is flowability important in drug formulation?

It affects the manufacturability and quality of solid dosage forms

How can polymorphism influence drug manufacturing?

Different polymorphs may have varied flow properties and compressibility

What is dissolution rate, and why is it important?

The speed at which a drug dissolves, critical for its absorption

How does solubility depend on pH?

Drugs may have pH-dependent solubility, affecting absorption at physiological pH

What factors influence solubility in polymorphs?

Packing efficiency, intermolecular interactions, and Gibbs free energy

Why is the most stable polymorph often used in formulations?

It minimizes the risk of conversion to other forms during storage

How can metastable polymorphs benefit drug formulations?

They may enhance solubility and bioavailability despite lower stability

How did polymorphism affect the development of Ritonavir?

A less soluble polymorph (Form II) appeared post-market, leading to reduced bioavailability and financial losses

What are the challenges of using polymorphs in bioequivalence?

Different polymorphs can result in varying dissolution rates and therapeutic efficacy