Exam 1 - Basics Flashcards
Drug considerations in dosage form development:
- aqueous solubility, pKa, partition coefficient
* stability in solution
Biopharmaceutical considerations in dosage form development:
- site of action – local? systemic?
- site, mechanism, and extent of absorption
- first pass metabolism?
- desired onset / duration of action
Drug Product:
- dissolution, skin permeability
- storage stability, rate of degradation, storage restrictions
- packaging
- excipient compatibility
- patient compliance – taste, smell, mouth-feel, size, dosing frequency, “pharmaceutical elegance”
“Manufacturability”:
- powder flow / powder & tablet compaction
- robust process
- cost of goods
- quality control/assurance
Pharmaceutics is:
the science of pharmaceutical systems and application to the
design and manufacture of dosage forms
Science of pharmaceutics incorporates:
- physical pharmaceutics (chemistry)
- biopharmaceutics
- dosage form design
- manufacturing scale – small, intermediate, large
- microbiology
- product performance/quality testing
Drug:
Active Pharmaceutical Ingredient (API)
Drug Product:
Dosage Form/Drug-Delivery System
Goal of Dosage Form Design:
“Achieve a predictable, reproducible, therapeutic response in a dosage form that is amenable to large-scale manufacture” of predefined and controlled product quality.
Important dosage form characteristics:
- stability (chemical/physical)
- uniformity of dosage units
- patient/prescriber acceptability
- appropriate packaging & labeling
- protection from microbial contamination
Chemical properties of API:
solubility
particle size,
crystalline/amorphous form
Dosage form/API is determined by:
- convenient and efficacious treatment of the disease
- most direct and effective route of delivery to the disease target
- minimize exposure at systemic targets unrelated to disease (minimize adverse effects)
Factors guiding design of dosage forms:
- Biopharmaceutics
- Physicochemical characteristics of the
active pharmaceutical ingredient (API) - Therapeutic intent – drug target / indication / patient satisfaction
Biopharmaceutical Considerations for Dosage Form Design:
• Drug must be in solution
• Absorption generally via passive diffusion or carrier
mediated transport
• Passive diffusion rate – lipid solubility & degree of ionization
• Knowledge of transport carriers/mechanisms can guide drug design
Routes of administration that allow drug to be absorbed directly into systemic circulation:
buccal respiratory rectal im sc
Routes of administration that allow drug to be directly delivered into systemic circulation:
Intravenous
Barriers to systemic circulation when drug is administered orally:
GI transit time, absorption rate, portal circulation with potential first pass clearance
Rectal administration:
- generally for local effects
- useful for drugs inactivated by the GI environment via oral route
- vomiting or unconscious patients
- avoids first pass
- inconvenient and absorption can be irregular
Parenteral administration:
SC, IM, IV, intracardiac, intrathecal
Particle size affects:
- dissolution rate
- absorption rate
- product content uniformity and stability
Solubility affects passive absorption:
- low solubility – erratic or incomplete absorption
- pH
- can be enhanced by particle size reduction; complexation with hydrophilic polymers (e.g., cyclodextrins)
- can be diminished by excipients (lubricants) or manufacturing processes (over blending, over compaction)
Noyes-Whitney Equation:
The process by which molecules of a solid in contact with a liquid leave the solid phase and form a one-phase, homogeneous, molecular mixture with the solvent.
Biopharmaceutics Classification System (BCS):
Class I high solubility/high permeability propranolol; metoprolol
Class II low solubility/high permeability ketoprofen; carbamazepine
Class III high solubility/low permeability ranitidine; atenolol
Class IV low solubility/low permeability hydrochlorothiazide; furosemide
Therapeutic Considerations in Dosage Form Design:
Delivery of API based on indication
Patient population