3.2 Sterile & Non-Sterile Compounding

Why Compounding Matters on the NAPLEX

Compounding sits squarely in NAPLEX Area 2 and overlaps with the foundational calculations domain. The United States Pharmacopeia (USP) publishes the enforceable general chapters that define how compounded preparations must be made and dated. Exam items test whether you can apply the correct chapter, assign a defensible beyond-use date, recognize an incompatibility, and perform the supporting calculation accurately.

The Three Core USP Chapters

A preparation can fall under more than one chapter at once. A compounded sterile hazardous injection is governed by both <797> (sterility) and <800> (hazardous handling).

Non-Sterile Compounding (USP <795>)

USP <795> covers preparations such as oral suspensions, capsules, topical creams, and ointments that are not required to be sterile. Core principles tested on the NAPLEX:

• Master formulation and compounding records document ingredients, lot numbers, calculations, and the assigned beyond-use date.
• Ingredient quality — use USP/NF grade substances when available; document the source.
• Beyond-use date (BUD) is assigned by formulation category and storage, and is a maximum; it can be shorter if stability data require.
• Equipment and weighing — use a balance within its accurate weighable range; the minimum weighable quantity protects accuracy.

The BUD answers "how long is this preparation safe and stable to use," which is different from the manufacturer expiration date of a bulk ingredient. A compounded BUD is conservative and based on the lack of preservative, water activity, and known stability.

Sterile Compounding (USP <797>)

USP <797> governs compounded sterile preparations (CSPs) such as IV admixtures, parenteral nutrition, and ophthalmics. The objective is to prevent microbial contamination, excess endotoxin, and physical/chemical error.

Environment and Engineering Controls

• A primary engineering control (PEC) provides an ISO Class 5 critical work area: a laminar airflow workbench (LAFW) for non-hazardous CSPs or a biological safety cabinet (BSC)/containment isolator for hazardous CSPs.
• The PEC is placed in a cleaner-than-room buffer area with appropriate ISO classification and pressure relationships.
• First air — the clean air flowing directly from the HEPA filter must not be interrupted between the filter and the critical site.

Aseptic Technique

Aseptic technique is the set of behaviors that keep the critical site sterile: hand hygiene and garbing in the correct order, disinfecting the critical site and PEC with sterile 70% isopropyl alcohol, working without blocking first air, and not introducing shedding or contamination into the critical area. Beyond-use dating for CSPs depends on the assigned microbial risk level/category and storage temperature, with shorter BUDs for higher-risk preparations and room-temperature storage.

Hazardous Drug Handling (USP <800>)

USP <800> protects personnel, patients, and the environment from exposure to hazardous drugs (HDs) — drugs identified by the National Institute for Occupational Safety and Health (NIOSH) as carcinogenic, teratogenic, genotoxic, or otherwise harmful at low exposure (many antineoplastics, some hormones, and others).

Key requirements tested on the NAPLEX:

• Containment primary engineering control (C-PEC) — for example, a Class II biological safety cabinet or compounding aseptic containment isolator, vented appropriately.
• Negative pressure in the HD compounding room relative to adjacent space, with the C-PEC in a containment secondary engineering control (C-SEC).
• Personal protective equipment (PPE) — ASTM-tested chemotherapy gloves (often double-gloved), gowns, and respiratory/eye protection per the assessment of risk.
• Closed-system transfer devices (CSTDs) are recommended for compounding and required for administration when the dosage form allows.
• Dedicated equipment, spill kits, deactivation/decontamination procedures, and HD-specific waste streams.

A preparation that is both sterile and hazardous must satisfy <797> sterility requirements and <800> containment requirements simultaneously.

Stability, Incompatibility, and BUD

Stability is the extent to which a preparation retains, within limits, the same properties it had at the time of compounding. NAPLEX items distinguish:

• Physical incompatibility — visible change such as precipitation, haze, color change, or gas formation (a classic example is calcium and phosphate precipitation in parenteral nutrition at high concentrations).
• Chemical incompatibility/degradation — loss of potency or formation of a new compound, often pH- or light-driven (for example, hydrolysis or oxidation).
• Therapeutic incompatibility — an undesirable interaction when two agents are combined.

The assigned beyond-use date (BUD) integrates the governing USP chapter, the formulation, storage temperature, container, and available stability data. When in doubt, the more conservative (shorter) BUD applies. The BUD is never simply copied from a bulk ingredient's manufacturer expiration date.

Compounding Calculations

Area 2 frequently pairs a compounding scenario with a calculation. Master these:

• Percentage strength — % w/v is grams of solute per 100 mL; % w/w is grams per 100 g; % v/v is mL per 100 mL.
• Dilution and concentration — the quantity of active ingredient is conserved: (C1 × Q1) = (C2 × Q2).
• Alligation — used to combine two strengths to reach a desired intermediate strength; the parts of each component are proportional to the difference between the other component and the target.
• Aliquot method — used when a required quantity is below the balance's minimum weighable quantity: weigh a larger, accurately weighable amount, dilute, and measure the proportional aliquot.
• Reducing/enlarging a formula — scale every ingredient by the same factor (desired total ÷ formula total).

Worked Example: Percentage Strength

How many grams of hydrocortisone are in 60 g of a 2.5% w/w ointment? 2.5% w/w = 2.5 g per 100 g. (2.5 g ÷ 100 g) × 60 g = 1.5 g of hydrocortisone.