Pre-Formulation Considerations in Drug Development

Flashcards covering key concepts from the lecture on preformulation considerations in drug development.

Preformulation is the investigation of and properties of a new drug substance.

physical and chemical

The primary objective of preformulation is to formulate and dosage forms.

stable and effective

Physical properties include physical description, particle size, crystalline structure, __, and solubility.

melting point

Liquid drugs can be formulated into solid dosage forms only with __ modification.

chemical

The amount of heat absorbed when 1 g of drug substance vaporizes is referred to as __.

heat of vaporization

The percentage of a specified compound or element in an impure sample is called __.

purity

Melting point is defined as the temperature at which solid and liquid exist in __.

equilibrium

The phenomenon where the melting point of a material decreases with a reduction in its size is called __.

melting point depression

Differential Scanning Calorimeters (DSC) measure temperatures and __ associated with thermal transitions.

heat flows

Most physical and chemical properties of drug substances are affected by particle size, including __ and bioavailability.

dissolution rate

Polymorphism is the ability of a solid material to exist in more than one form of __ structure.

crystal

Incompatibility with excipients can lead to physical or __ incompatibility resulting in undesirable products.

chemical

Chemical stability refers to each active ingredient retaining its chemical integrity and labeled __ within specified limits.

potency

Hydrolysis involves drug molecules interacting with __ molecules to yield breakdown products.

water

Decomposition by light is known as __.

photolysis

Polymorphs can cause variations in __, compressibility, and melting point.

solubility

Factors affecting physical stability include temperature, pH, __, air, and humidity.

light

To prevent the effects of air on drug stability, containers should be packed tightly and filled as __ as possible.

full

The presence of oxygen can induce degradation through __.

oxidation

Ionic strength is the concentration of __ in a solution.

electrolytes

The smaller the particle size, the greater the __ due to increased surface area.

reactivity

Dissolution rate is the time it takes for the drug to __ in the fluid.

dissolve

For drugs to exert a therapeutic effect, they must first be in __.

solution

Chemical modification can involve converting the drug into __ or ester forms to increase solubility.

salt

The movement of molecules varies with __, affecting how substances transition states.

temperature

Pure crystalline solids have a defined __ and melting point that can indicate their purity.

melting point

Chromatography techniques may be used to detect __ in drug substances.

impurities

__ is the ability of a compound to exist in multiple crystalline forms, affecting its properties.

Polymorphism

The main goal of the R&D procedure in drug development is to identify leading APIs and __ them.

optimize

Liquid drugs often require special designs to prevent __ loss due to high volatility.

evaporation

Surfactants may be added to improve the __ of immiscible mixtures.

miscibility

Thermal analysis techniques like TGA measure weight changes in materials as a function of __.

temperature

The __ degrades drugs by exposing them to light, which can accelerate chemical reactions.

photolysis

The technique used to determine crystal properties may include hot stage microscopy and __ spectroscopy.

infrared

The dissolution rate can significantly affect the overall __ of a drug from its dosage form.

bioavailability

describes the process of a solid dissolving in a solvent.

Dissolution

Excipients can sometimes cause __ with active ingredients if they form undesirable products.

incompatibility

General acid and base catalysis may affect reaction rates based on the presence of __ ions.

hydroxide and/or hydrogen

The rate of degradation reactions can often be represented by __ curves.

pH vs. Rate of degradation

Adding antioxidants can help minimize the effects of __ in drug formulations.

oxidation

Appropriate packaging like amber bottles can help minimize the effects of __ on drugs.

light

The improper mixing of two substances can affect their physical properties, resulting in __ incompatibility.

physical

stability refers to the maintenance of sterility in pharmaceutical products.

Microbiological

The hydrolysis of aspirin results in the formation of salicylic acid and __ acid.

acetic

Using a highly water-soluble __ of the parent substance can achieve higher dissolution rates.

salt

Increasing temperatures typically increase the rates of __ reactions.

chemical

Solutions with a low dielectric constant may accelerate reactions involving ions of __ charge.

opposite

High-performance liquid chromatography (HPLC) is used to detect __ related impurities.

organic

Particle size affects the __ rate, which can influence drug absorption.

dissolution

Spherical powders tend to flow more freely than __ powders in pharmaceutical applications.

needle-shaped

If a liquid drug is intended for oral administration, it cannot typically be formulated into __ without modification.

tablet form

Thermo Gravimetric Analysis (TGA) is useful for determining the presence of water or other __ solvents in drugs.

residual

To enhance drug bioavailability, it may be necessary to reduce __ size.

particle

An increased __ can lead to the formation of insoluble carbonates with solid dosage forms.

CO2

Chemical reactions like reduction, oxidation, and hydrolysis represent mechanisms of __ instability.

chemical

Polymorphism can influence __ availability, chemical stability, and dosage form processes.

bioavailability

For a drug to enter systemic circulation, it must first resolve its physical state into a __.

solution

Impurities in a drug product can affect stability and potentially introduce __ properties.

toxic

The modifications made to a liquid drug may include converting it to a solid __ or salt form for tablet formulation.

ester

Solubility is highly dependent on the __ forms of acids and bases involved.

pH-dependent

Differential Scanning Calorimetry measures heat flows during thermal __ in materials.

transitions

Polymorphs in pharmaceutical drugs may exist in both __ and non-crystalline forms.

crystalline

Drug formulations generally require a balance between stability and __ factors.

efficacy

Physical instability can result from temperature fluctuations leading to __ in drug formulations.

crystallization

Chemical instability may produce toxic substances during the __ of active ingredients.

degradation

Reconstituting a drug just before dispensing minimizes solvent __ effects.

stability

The formation of __ variably affects solubility, compressibility, and melting point.

polymorphs

Substances that result from chemical reactions can include unexpected byproducts that lead to __ reactions.

toxic

The Henderson-Hasselbalch equation relates pH to the __ of acid-base drugs.

solubility

Incompatibility arises when mixed substances form undesirable __ products.

chemical