Absorption of drugs from non-oral extravascular routes is a vital area in pharmaceutics and pharmacokinetics for B.Pharm students. This topic covers how drugs enter systemic circulation when administered via routes such as transdermal, sublingual, buccal, nasal, pulmonary, rectal, vaginal, intramuscular, and subcutaneous. Key concepts include permeability barriers, Fick’s law, pKa and ionization, lipid solubility, blood flow, formulation factors, lymphatic uptake, local metabolism, and bioavailability. Understanding these principles helps optimize therapeutic effect and minimize adverse reactions. Mastery of route-specific factors and absorption kinetics is essential for dosage form design and clinical application. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which factor most directly increases transdermal drug absorption?
- Increasing drug molecular weight
- Enhancing skin hydration
- Decreasing drug lipophilicity
- Applying at a cold temperature
Correct Answer: Enhancing skin hydration
Q2. The main barrier to percutaneous absorption is:
- Stratum corneum
- Dermal capillaries
- Hypodermis fat layer
- Hair follicles
Correct Answer: Stratum corneum
Q3. Which route bypasses hepatic first-pass metabolism most effectively?
- Oral
- Rectal (upper rectum)
- Sublingual
- Gastrostomy
Correct Answer: Sublingual
Q4. For a weakly basic drug, absorption from vaginal route is favored when the vaginal pH is:
- Much higher than pKa
- Much lower than pKa
- Equal to pKa
- Irrelevant to pKa
Correct Answer: Much higher than pKa
Q5. Which statement about intramuscular (IM) injections is correct?
- IM absorption is independent of blood flow
- IM injections always provide slower absorption than subcutaneous
- IM absorption can be increased by massage
- IM route bypasses lymphatic uptake
Correct Answer: IM absorption can be increased by massage
Q6. Lymphatic uptake of drugs is most important for:
- Very small hydrophilic molecules
- Large lipophilic molecules and lipophilic drug-lipid complexes
- Strong acids with low molecular weight
- Inorganic ions
Correct Answer: Large lipophilic molecules and lipophilic drug-lipid complexes
Q7. Which formulation strategy enhances nasal absorption of peptides?
- Increase enzymatic degradation
- Include protease inhibitors
- Lower residence time in nasal cavity
- Reduce mucoadhesive properties
Correct Answer: Include protease inhibitors
Q8. The primary mechanism for drug uptake across alveolar epithelium (pulmonary route) is:
- Active transport via carriers
- Endocytosis only
- Passive diffusion across the epithelial membrane
- Filtration through tight junctions exclusively
Correct Answer: Passive diffusion across the epithelial membrane
Q9. Which factor does NOT significantly affect subcutaneous absorption?
- Local blood flow
- Particle size of suspension
- Ambient temperature
- Gastric pH
Correct Answer: Gastric pH
Q10. Buccal absorption is especially useful for drugs that:
- Have extensive hepatic first-pass metabolism
- Require delivery to the colon
- Are unstable in saliva
- Are highly ionized at buccal pH
Correct Answer: Have extensive hepatic first-pass metabolism
Q11. Which property favors passive diffusion across biological membranes?
- High molecular weight and high polarity
- High lipophilicity and low molecular weight
- Strong ionization at physiological pH
- Strictly charged molecules
Correct Answer: High lipophilicity and low molecular weight
Q12. Rectal administration can partially avoid first-pass metabolism because:
- All rectal veins drain to hepatic portal vein
- Lower rectal veins drain directly to systemic circulation
- Rectal mucosa has no enzymes
- Rectal pH completely ionizes all drugs
Correct Answer: Lower rectal veins drain directly to systemic circulation
Q13. Which enhancer mechanism increases transdermal drug delivery?
- Strengthening hydrogen bonding in stratum corneum
- Extracting lipids from stratum corneum to increase permeability
- Decreasing drug solubility in the vehicle
- Raising skin electrical resistance
Correct Answer: Extracting lipids from stratum corneum to increase permeability
Q14. Tmax after sublingual administration compared to oral administration is generally:
- Longer due to slower absorption
- Shorter due to rapid transmucosal uptake
- Identical always
- Dependent only on gastric emptying
Correct Answer: Shorter due to rapid transmucosal uptake
Q15. Which ocular route factor limits drug absorption into the anterior chamber?
- Tear turnover and nasolacrimal drainage
- High corneal permeability for hydrophilic drugs
- Absence of corneal epithelium
- Presence of a continuous capillary network in cornea
Correct Answer: Tear turnover and nasolacrimal drainage
Q16. The Henderson-Hasselbalch concept is important for extravascular absorption because it predicts:
- Drug crystalline polymorphism
- Fraction of drug ionized at a given pH
- Protein binding percentage only
- The dissolution rate in gastric fluid
Correct Answer: Fraction of drug ionized at a given pH
Q17. Depot formulations given intramuscularly prolong absorption mainly by:
- Rapidly increasing local blood flow
- Providing a slow-release reservoir at injection site
- Converting drug to highly water-soluble salt
- Immediate systemic clearance
Correct Answer: Providing a slow-release reservoir at injection site
Q18. Which nasal delivery attribute enhances systemic absorption of small molecules?
- High mucociliary clearance rate
- Large surface area and rich vascularization of nasal mucosa
- Thick keratinized epithelium
- Poor blood supply
Correct Answer: Large surface area and rich vascularization of nasal mucosa
Q19. Which statement best describes bioavailability (F) for non-oral extravascular routes?
- F is always equal to 1 (100%) for extravascular routes
- F can be less than 100% due to local metabolism, incomplete absorption, or binding
- F only depends on dose volume
- F is not influenced by formulation
Correct Answer: F can be less than 100% due to local metabolism, incomplete absorption, or binding
Q20. Which excipient is commonly used to improve transdermal drug partitioning into skin?
- Hydrophobic polymer with low solubility
- Oleic acid as a chemical penetration enhancer
- Sodium chloride crystals
- Polymers that decrease drug solubility in vehicle
Correct Answer: Oleic acid as a chemical penetration enhancer
Q21. Which route is preferred for rapid systemic effect of emergency drugs without IV access?
- Transdermal patch
- Intramuscular injection
- Topical cream
- Vaginal suppository
Correct Answer: Intramuscular injection
Q22. For inhalation therapy, particle size between 1–5 µm is ideal because it:
- Deposits in oropharynx predominantly
- Reaches lower respiratory tract and alveoli
- Is exhaled without deposition
- Causes immediate systemic toxicity
Correct Answer: Reaches lower respiratory tract and alveoli
Q23. Which condition will decrease absorption from subcutaneous depot of an insulin suspension?
- Increased local blood flow due to heat
- Injection into highly perfused muscle
- Formation of a crystalline depot that slows dissolution
- Administration of a low-viscosity solution
Correct Answer: Formation of a crystalline depot that slows dissolution
Q24. Mucoadhesive formulations for buccal or nasal delivery primarily aim to:
- Decrease contact time with mucosa
- Increase residence time and absorption
- Promote rapid mucociliary clearance
- Prevent any drug permeation
Correct Answer: Increase residence time and absorption
Q25. Which of the following increases rectal mucosal absorption of a drug?
- Formulating as a poorly water-soluble waxy base only
- Using a suppository base that melts at body temperature
- Maximizing particle agglomeration
- Minimizing contact with rectal mucosa
Correct Answer: Using a suppository base that melts at body temperature
Q26. Enzymatic degradation is a significant barrier for which non-oral route?
- Sublingual route for small lipophilic drugs
- Nasal and pulmonary routes for peptides and proteins
- Transdermal for nonpolar molecules
- Intramuscular for inorganic ions
Correct Answer: Nasal and pulmonary routes for peptides and proteins
Q27. Which parameter best describes the rate of absorption from a non-oral extravascular route?
- Bioavailability (F)
- Absorption rate constant (ka)
- Elimination half-life (t1/2)
- Volume of distribution (Vd)
Correct Answer: Absorption rate constant (ka)
Q28. Which of the following increases nasal systemic absorption of small molecules?
- High mucociliary clearance and low residence time
- Use of mucoadhesive polymers to prolong contact
- Strongly basic drug ionized at nasal pH
- Large particulate suspensions >50 µm
Correct Answer: Use of mucoadhesive polymers to prolong contact
Q29. A major advantage of transdermal delivery over oral is:
- Increased hepatic first-pass metabolism
- Steady plasma levels and improved patient compliance
- High fluctuation in plasma concentration
- Requirement for large frequent dosing
Correct Answer: Steady plasma levels and improved patient compliance
Q30. Which formulation approach can protect peptides from degradation in nasal or pulmonary delivery?
- Co-administration with proteases
- Encapsulation in nanoparticles or liposomes
- Using highly aqueous, enzyme-rich vehicle
- Reducing contact time to seconds
Correct Answer: Encapsulation in nanoparticles or liposomes
