Pharmaceutical Excipients Overview

Polymorphism

• Drug substances can exist in more than one crystalline form with different internal lattice arrangements
• Polymorphic forms can vary in properties such as solubility, hygroscopicity, diffusivity, dissolution rate, melting point, or stability
• Different polymorphic forms can influence therapeutic efficacy, stability, and manufacturing ability of a dosage form
• Solvates (pseudopolymorphs) contain entrapped solvent within their structure, affecting their properties
• Aqueous solubility of hydrate compounds can be significantly less than their anhydrous forms
• The most stable polymorph typically has the highest melting point and lowest solubility

Stability of Oxidizable Drugs

• Trace metals can catalyze oxidation reactions, affecting drug stability
• Light can also act as a catalyst for oxidation reactions
• Temperature, pH, and chelating agents can affect the stability of oxidizable drugs
• Packaging in light-resistant or opaque containers can help maintain stability

Racemization

• Racemization is the conversion of an optically active compound into its inactive, racemic mixture
• This can affect the pharmacological activity of the drug
• For example, levo-adrenaline is 15-20 times more active than dextro-adrenaline

Polymerization

• Polymerization is a continuous reaction between molecules, resulting in a polymer
• This can affect the flow properties of drug powders
• Methods such as angle of repose, flow through an orifice, compressibility index, and shear cell can measure flow properties

Crystallinity

• Crystallinity refers to the internal structure of a crystal
• Crystal morphology (habit) can influence properties such as powder flow properties, compaction, and stability
• A single internal structure can have multiple habits, depending on the environment during crystal growth

Amorphous Form

• Amorphous forms are non-crystalline, possessing no long-range order
• These forms are thermodynamically unstable and tend to revert to a more stable form
• Amorphous compounds can have a decrease in chemical stability
• Stable amorphous compounds can have better bioavailability, such as the stabilized amorphous form of novobiocin

Pharmaceutical Excipients

• Pharmaceutical excipients are inactive, non-medicinal substances intentionally included in a drug product
• Examples include bulking agents, disintegrants, stabilizers, solvents, lubricants, binders, and preservatives
• Excipients ensure the drug product is acceptable to regulatory authorities and patients in terms of manufacturability, appearance, and therapeutic efficacy

Classification of Dosage Forms

• Dosage forms can be classified based on the method or route of administration or physical form
• Classification based on route of administration includes oral, parenteral, topical, and other routes

Bioavailability and Pharmacokinetics

• Bioavailability is determined by measuring pharmacokinetics in subjects following intravenous doses for reference and the intending dosing route
• Bioavailability is calculated as the ratio of the dose-normalized AUCs from the extravascular and intravenous routes
• Bioavailability may differ between species, making these studies critical in preclinical and clinical stages of drug research and development