North American Pharmacist Licensure Examination (NAPLEX) Pharmaceutics, Compounding, and Drug Delivery Syllabus

What does USP <800> address?

Standards for safe handling of hazardous drugs (HDs) to protect personnel, patients, and the environment — covering receipt, storage, compounding, dispensing, administration, and disposal.

What type of containment device and room pressure are required for compounding sterile hazardous drugs under USP <800>?

A containment primary engineering control (C-PEC, e.g., BSC or CACI) inside a negative-pressure ISO Class 7 buffer room (C-SEC) with at least 12 air changes per hour and external venting.

What reference defines the list of hazardous drugs used by USP <800>?

The NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings.

What is aseptic technique?

A set of practices that prevent microbial contamination of sterile products by maintaining sterility of critical sites and surfaces — including proper garbing, hand hygiene, first-air protection, and disinfection with sterile 70% isopropyl alcohol.

What is 'first air' and why must it never be blocked?

First air is the air directly emerging from the HEPA filter, which is essentially particle-free. Objects placed between the HEPA filter and a critical site disrupt first air and can introduce contamination (shadowing).

List common chemical degradation pathways of drugs.

Hydrolysis (esters, amides), oxidation, photolysis (light-induced), reduction, racemization, decarboxylation, and deamidation.

Give examples of physical degradation/instability of dosage forms.

Polymorphic transformation, crystal growth, caking of suspensions, creaming/cracking of emulsions, vaporization/sublimation, and moisture absorption (deliquescence).

Which functional groups are most susceptible to hydrolysis, and how is it minimized?

Esters and amides (also lactams/lactones). Minimized by adjusting pH to the region of maximum stability, reducing water content, lowering temperature, and using buffers.

How is oxidative degradation typically prevented in formulations?

Add antioxidants (e.g., ascorbic acid, sodium metabisulfite, BHT, BHA), use chelating agents (e.g., EDTA) to bind catalytic metals, displace oxygen with nitrogen, and protect from light.

Define an excipient and name five functional categories.

An excipient is an inactive ingredient added to a formulation. Categories: diluents/fillers, binders, disintegrants, lubricants, glidants, coatings, preservatives, sweeteners/flavors, and suspending/emulsifying agents.

What is the role of a disintegrant versus a lubricant in a tablet?

A disintegrant (e.g., croscarmellose, sodium starch glycolate) promotes tablet breakup in fluid to aid dissolution. A lubricant (e.g., magnesium stearate) reduces friction between tablet and die wall during ejection.

Why is magnesium stearate added in small quantities and added late in blending?

It is a hydrophobic lubricant; excess or overblending coats particles, retarding dissolution and weakening tablet bonding. It is typically used at roughly $0.25\%-2\%$.

How does pH affect the solubility of a weakly acidic drug?

A weak acid becomes more ionized and therefore more water-soluble as pH increases above its $pK_a$. Conversely, low pH favors the nonionized, less-soluble form.

What is the purpose of a buffer in a pharmaceutical formulation?

To resist changes in pH, maintaining drug stability, solubility, and physiological compatibility. Common buffers include acetate, citrate, and phosphate systems.

Name commonly used antimicrobial preservatives in aqueous formulations.

Benzalkonium chloride (ophthalmics), parabens (methyl/propylparaben), benzyl alcohol, chlorobutanol, phenol, and thimerosal/EDTA combinations.

Why must preservatives be avoided in certain parenteral products, and which patients are most at risk?

Benzyl alcohol can cause 'gasping syndrome' and toxicity in neonates; many large-volume and intrathecal/epidural products must be preservative-free. Neonates and patients receiving large volumes are most at risk.

Define the USP controlled room temperature range and refrigerated storage range.

Controlled room temperature: $20-25\,^{\circ}\text{C}$ (excursions $15-30\,^{\circ}\text{C}$). Refrigerated: $2-8\,^{\circ}\text{C}$. Frozen typically $-25$ to $-10\,^{\circ}\text{C}$.

What is the cold chain and why is it critical for vaccines and biologics?

The cold chain is the uninterrupted temperature-controlled supply and storage system (often $2-8\,^{\circ}\text{C}$). Temperature excursions can denature proteins and inactivate vaccines, reducing efficacy and safety.

What does 'protect from light' storage require, and give a light-sensitive drug example.

Storage in light-resistant (amber) containers, foil overwraps, or opaque covering during administration. Examples: nitroprusside, amphotericin B, and phytonadione.

What key incompatibility makes calcium and phosphate a concern in IV admixtures (especially TPN)?

Calcium and phosphate can form insoluble calcium phosphate precipitate, which can be fatal (pulmonary emboli). Risk increases with high concentrations, high pH, and high temperature; use organic phosphate salts and add phosphate first.

Differentiate physical, chemical, and therapeutic incompatibility in IV admixtures.

Physical: visible change (precipitate, color, gas, haze). Chemical: molecular degradation/reaction (often invisible). Therapeutic: pharmacologic interaction altering efficacy or toxicity when drugs are combined.

What classic incompatibility involves ceftriaxone and calcium-containing solutions?

Ceftriaxone forms an insoluble ceftriaxone–calcium precipitate; it is contraindicated to co-administer with calcium-containing IV solutions, especially in neonates.

List the major macronutrient components of total parenteral nutrition (TPN).

Dextrose (carbohydrate/energy), amino acids (protein), and intravenous lipid emulsion (fat/energy and essential fatty acids).

What micronutrient additives are routinely included in TPN?

Electrolytes (Na, K, Cl, Ca, Mg, phosphate, acetate), trace elements (zinc, copper, manganese, chromium, selenium), and multivitamins.

What is a '3-in-1' (total nutrient admixture) TPN, and what is a stability concern?

A 3-in-1 combines dextrose, amino acids, and lipids in one bag. Lipid emulsions can crack/destabilize at low pH or high electrolyte (especially divalent cation) concentrations, and precipitates cannot be seen through the opaque emulsion.

How do transdermal patches deliver drugs, and what is a key requirement of suitable drugs?

They provide controlled drug delivery across intact skin into systemic circulation, bypassing first-pass metabolism. Suitable drugs are potent (low dose), lipophilic, and low molecular weight to cross the stratum corneum.

For pulmonary/inhalation delivery, what particle aerodynamic diameter optimizes deep lung deposition?

Particles of roughly $1-5\,\mu\text{m}$ aerodynamic diameter reach the lower airways/alveoli. Larger particles ($>5\,\mu\text{m}$) deposit in the oropharynx; very small ones are exhaled.

Why are ophthalmic solutions formulated to be isotonic and near-neutral pH?

To minimize irritation, reflex tearing, and drug washout. Isotonicity matches tear tonicity ($\approx 0.9\%$ NaCl equivalent) and a near-physiologic pH improves comfort and corneal absorption.

What is the maximum volume typically given by a single intramuscular injection in the deltoid versus gluteal sites?

Deltoid: about $1-2\,\text{mL}$. Larger gluteal/vastus lateralis sites: up to about $3\,\text{mL}$ (up to $5\,\text{mL}$ in some adult gluteal cases). Larger volumes increase pain and poor absorption.

Calculate the milliosmolarity contribution: why does dextrose 5% in water (D5W) have an osmolarity of about 252 mOsm/L?

D5W contains $50\,\text{g/L}$ of dextrose (MW $\approx 198$ as monohydrate); $\frac{50}{198}\times 1000 \approx 252\ \text{mOsm/L}$, making it approximately iso-osmotic with plasma ($\approx 285\ \text{mOsm/L}$).