PHRM 6201: Physical Pharmacy - Drug Stability and Degradation Study Notes

PHRM 6201: Physical Pharmacy

Be able to understand drug stability and various aspects involved in drug stability
Be able to describe the factors related to drug stability
Be able to describe the role of packaging in drug stability
Be able to identify chemical reactions involved in drug degradation

NDC Code: 59148-046-70
Dosage form: 50 mg per vial
Administration route: For intravenous infusion only
Warning: Cytotoxic agent
Packaging: Single-dose sterile vial - discard unused portion
Storage conditions: Store vials at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) per USP Controlled Room Temperature guidelines.
Composition: Each vial contains 50 mg decitabine and other excipients including hydroxide, sodium hydroxide, phosphate for pH adjustment - 11.6 mg of sodium and 68 mg of monobasic potassium hydrochloric acid.
Further information regarding dosage, indications, reconstitution, and precautions is available in the package insert.
Expiration date based on approved shelf-life.

Physical Stability: Pertains to the drug's physical state, such as appearance, texture, and solubility.
Chemical Stability: Involves the drug's chemical integrity and resistance to degradation.
Microbial Stability: Relates to the drug's safety concerning microbial contamination and viability.
Organoleptic Properties: Sensory properties (taste, smell, appearance) crucial for patient acceptance.
Safety and Efficacy: Must be maintained throughout the drug's shelf life to ensure patient safety.

Hydrolysis: The chemical reaction whereby water interacts with a substance, leading to breakdown.
Oxidation: The process of reaction with oxygen leading to loss of electrons and change in molecular structure.
Photolysis: The breakdown of compounds due to light exposure.
Isomerization and Racemization: Conversion between different structural forms that may have different biological activities.
Drug-excipient Interactions: Reactions between the active ingredients and substances used in the formulation that can affect stability.

Catalyzed by acid or base.
Example Reactions:
- Involves conversion of an ester into a carboxylic acid and alcohol.
Reaction Example:

ext{C}
ext{R-O-C(=O)-R'} + H_2O
ightarrow ext{RCOOH} + ext{R'OH}

Activation of pro-drugs, e.g., conversion of aspirin (acetylsalicylic acid) to salicylic acid upon hydrolysis.

Common forms include the oxidation of thiol groups and primary alcohols, which may result in the formation of intermediate products.
Compounds may form complex degradation products after oxidation.

Cis-trans Isomerization: A reversible change due to the orientation of functional groups about a double bond.
Epimerization: A specific type of isomerization that involves a change in configuration at a single stereocenter.
Racemization: The conversion between enantiomers, altering the effectiveness and safety profile of the drug.

General expressions for reaction rates that describe how quickly a reactant is consumed or a product is formed.
Example: Rate of loss of A in an isomerization reaction is equal to the rate of formation of D
ext{A}
ightarrow ext{D}
For dimerization, the rate of loss of A is twice that of formation of D
2 ext{A}
ightarrow ext{D}

The stability of pharmaceutical formulations is paramount to ensure their safety and efficacy for patients. Understanding the various interacting factors and chemical reactions is essential for pharmacy professionals. Comprehensive knowledge helps in effective storage, handling, and formulation development to maintain drug integrity throughout its shelf life.