Video Summary - CNSP Lecture - Creams & Ointments (semi-solids)

Main ideas / lessons conveyed

Semi-solid dosage forms include creams and ointments, both intended for external use on skin or mucous membranes.
Distinguishing “cream vs ointment” has historically been confusing because older definitions overlap.
Modern practice relies on revised definitions and base composition, since the base strongly influences:
- Physical feel
- Water handling
- Drug delivery
- Stability
- Patient acceptability

Definitions and distinguishing creams vs ointments

Traditional definitions (overlap → confusion)

Ointment (traditional): semi-solid preparation for external application to skin or mucous membranes.
Cream (traditional): semi-solid dosage form with one or more drugs dissolved or dispersed in a suitable base.

Because these overlap, the same term could be used broadly under older usage.

Modern / revised definitions (manufacturer-oriented)

Ointment (modern): a viscous oleaginous or polymeric semi-solid dosage form.
- Base characteristics commonly include:
  - Hydrocarbon/oleaginous → greasy, thick, stiff
  - Not water-washable
- Examples: white petrolatum (e.g., Vaseline/Aquaphor-type hydrocarbon components) and similar hydrocarbon bases.
Cream (modern): drug incorporated into a viscous semi-solid emulsion.
- “Emulsion” matters because creams are typically:
  - Oil-in-water → white, soft, water washable
  - Or water-in-oil
  - Or water-soluble-type bases, depending on formulation
- Multiple emulsion systems exist → multiple “cream-like” products.

Why compound topical semi-solids (purpose of compounding)

The main reason to compound is to use the base as a vehicle to deliver the active drug to the skin.
The active drug may be intended for:
- Local effect (e.g., topical anti-infective for skin infection)
- Systemic effect via absorption (e.g., estrogen-containing cream for menopause symptoms)
Regardless of drug intent, base selection is crucial because the base contributes key properties.

Base properties to consider (what the base must do)

Three distinctive properties (core functions)

Molding / emollient action & relief
- Can soften skin and help with local irritation.
Protectant action
- Protects injured/exposed skin from harmful or discomforting stimuli.
Occlusive action
- Promotes water retention by forming a hydrophobic barrier.
- Reduces water evaporation/removal from skin.

Additional practical requirements for bases

Chemical and physical stability under normal storage/use
Nonreactive and compatible with many drugs and formulation agents
Free from objectionable odor
Non-toxic and non-irritating / non-sensitizing, especially for sensitive skin
Aesthetics & usability
- Generally non-greasy and easy to apply
Proper residence time
- Must remain on skin until removal is desired
- Preferably removable with water when applicable

How to choose whether the formulation should be a cream or an ointment (base choice logic)

The choice depends on three main factors:

Nature of the drug
- Must be bioavailable (readily absorbed from the base)
- Consider stability/compatibility:
  - Water-containing bases may promote drug hydrolysis/inactivation
  - Drug may change pH, reducing emulsifier effectiveness
Desired base properties
- Choose base to provide:
  - Emollience/softening (molding)
  - Protection
  - Occlusion / water retention
Area of application
- May be applied to skin, eyes, rectal, or vaginal sites
- Must be compatible and non-irritating for that location

Safety / authority instruction

If a prescription specifies a particular base and it’s not compatible with the prescribed drug:
- Consult the prescriber
- Pharmacists should not change the base without prescriber approval

The five classes of semi-solid bases (pharmacist must recognize)

The lecture frames five base categories, with distinct physical behavior:

Hydrocarbon / oleaginous bases
- Examples: petrolatum, white petrolatum
- Characteristics:
  - Greasy, stiff; yellowish or white (decolorized)
  - Cannot absorb water
  - Not water-washable; limited alcohol uptake
Anhydrous absorption bases
- Example: Aquaphor
- Characteristics:
  - Similar look to hydrocarbon bases
  - Contains emulsifier → can absorb/hold some water despite being “anhydrous”
Water-and-oil emulsion absorption bases
- Example: Eucerin
- Characteristics:
  - Often looks “cream-like,” but behaves as an emulsion system
  - Contains water → can absorb additional water (to a limit)
Water-removable bases (oil-in-water emulsion bases)
- Examples: vanishing creams / Velva-type product (as referenced in subtitles)
- Characteristics:
  - Water is the external phase
  - Soft, light, water washable
  - Can accept water/water-miscible liquids in the external phase
  - Not very occlusive compared with earlier classes
Water-soluble bases
- Examples: poly bases / polyethylene glycol ointment-type bases
- Characteristics:
  - Soluble in water and alcohol
  - Accept limited water/alcohol without losing viscosity
  - Non-greasy, easy to wash off
  - Limited emollient effect; may be irritating to denuded skin/mucosa
  - Some PEG types can have drug compatibility issues

Preparation & compounding: goals and procedures (instructional bullets)

Compounding goal #1: produce a homogeneous (well-blended) product

Core challenge: solids may be present as powders → must be dispersed evenly.
Typical tools:
- Ointment pad (paper-like surface)
  - Pros: no cleanup
  - Cons: may absorb aqueous liquids; can tear with sticky bases
- Ointment slab (ceramic/glass)
  - Pros: handles liquids well; reusable
  - Cons: must be cleaned thoroughly afterward
Tools for mixing:
- Spatulas and rubber policemen
- Spatula selection:
  - Metal spatulas for lifting/dispensing powders and product
  - Rubber policemen for scraping in mortar situations
Special processing:
- Ointment mill (rollers)
  - Reduces particle size (down to ~20 microns mentioned)
  - Improves homogeneity; minimizes grittiness
  - Reduces personnel exposure
- Electric mixers may be used for automated emulsions/creams

Compounding goal #2: produce a product smooth, non-gritty

Ensure solids are at the finest particle size possible.
Strategies:
- Start with finer commercially available forms
- If a specific form is required by prescriber:
  - Use that form unless you contact prescriber to change
- Use mortar and pestle for most powders
- Use levigation / triturating to create smooth dispersion

Levigation (workflow concept)

Purpose: wet solids and reduce particle size using shear with a lubricating agent.
Conceptual method:
1. Place powder on ointment pad/slab
2. Make a small divot
3. Add small portions of levitating agent (e.g., glycerin/mineral oil)
4. Triturate/levigate until powder is completely wetted
5. Stop when no dry powder remains (thick paste formed)

Selecting an auxiliary levitating agent (minimized-change rule)

If formulation already includes an appropriate liquid ingredient → use it.
If not, choose based on compatibility with the base external phase:
- Hydrocarbon / anhydrous absorption / water-in-oil emulsion bases → mineral oil
- Oil-and-water emulsion / water-soluble bases → glycerin

General compatibility rule

Levigation agent should be chemically similar to the base’s external phase.

Choosing the quantity of levitating agent

Use the minimum amount needed to:
- Wet solids
- Lubricate
- Liquefy them enough for smooth mixing
Constraints:
- Too much can alter consistency (e.g., cream becomes too “lotion-like”)
- In emulsions, too much added liquid can crack or destabilize the emulsion

Documentation & calculations (step-by-step)

Account for excess formulation
- Prepare 10% excess (lecture practice) to allow for losses.
- Example: target 45 g → prepare 49.5 g
Calculate active ingredient quantity
- Use prescribed concentration (e.g., 10% w/w → active = 10% of final computed weight)
Determine levitating agent volume used
- Only determined after physically levigating powder (measure volume).
- Measure with syringe or graduated device.
Convert levitating agent volume to weight
- Use specific gravity as density:
  - Mineral oil SG ≈ 0.88
  - Glycerin SG ≈ 1.26
Compute remaining base weight
- Total prepared weight = base + active + levitating agent weight
- Base weight = (total prepared) − (active weight) − (levitating agent weight)

Lecture worked examples (concept summary)

Example 1: Zinc oxide 10% in an anhydrous absorption base
- Mineral oil used for levigation (base-compatible)
- Mineral oil volume measured (e.g., 2 mL)
- Convert volume to weight using SG
- Compute remaining base mass to reach total weight
Example 2: Zinc oxide 10% in a water-removable / oil-and-water emulsion base
- Glycerin used for levigation (base-compatible)
- Glycerin volume measured (e.g., 1.5 mL)
- Convert volume to weight using glycerin SG
- Compute remaining base mass to reach total weight

If the active ingredient is already a liquid

Levigation is not required for liquids like LCD (as referenced).
Key precautions:
- Base must be able to absorb the liquid
  - Failure example: liquid added to pure hydrocarbon vaseline → puddles on top
  - Fix: switch to an absorption base (e.g., aquaphor-type)
- Use careful technique:
  - Liquids can splash (low surface tension)
  - Consider a hard surface slab if liquid amount is significant
- Absorption takes time:
  - Add liquid gradually and triturate gently, using a depression/divot method

Preparation guidelines after compounding

Guideline 1: beyond-use dating (BUD) — stability-based

Use stability references when available.
If not available, use conservative estimates and monitor for instability signs:
- Discoloration
- Consistency changes
- Odor changes
Physical instability issues:
- Bleeding (separation of liquid ingredients via phase separation)
- Evaporation of water → drying/shrinking/cracking
- Granule formation & grittiness as base shrinks
Chemical instability considerations:
- Water-containing levigating agents (e.g., glycerin/water) can increase hydrolysis
- pH-sensitive emulsifiers → incompatible with acids (example includes vanishing creams and salicylic acid/phenolics)
Microbial instability:
- USP emphasizes that emulsions require antimicrobials
- Some commercial bases include preservatives, which may reduce the need for added preservatives
Default rule when no stability info/concerns:
- USP 795-based guidance mentioned: for water-containing topical dermal/mucosal products, BUD not later than 30 days

Guideline 2: packaging

Choose container type based on route/physical characteristics:
- Jars for thick/stiff ointments
- Tubes/pumps/syringes for better contamination control
Packaging should be tight:
- Minimize air exposure and microbial contamination
Jar-filling technique:
- Tap to remove air pockets
- Smooth/dress top for finish (“icing cake” analogy)
- Don’t overfill; avoid product sticking to lid threads

Guideline 3: quality control & labeling

Quality control / compounding record must include

Final weight
Visual appearance, color, odor (if any)
Viscosity/texture description

Prescription label must include

Active ingredient names and strengths (e.g., “Zinc oxide 10%, Calamine 5%”)
Commercial base name (because it affects product properties)
Route of application (e.g., topical; rectal/vaginal if applicable)
Dosage form (cream, ointment, paste)

Not on label (but documented in compounding record)

Auxiliary ingredients such as levitating agents (typically not listed on prescription label)
Patient warning labeling as relevant:
- Keep away from/restrict access by children

Speakers / sources featured

Dr. Speidel (TA/supervisor)
Dr. Lanky (TA/supervisor)
USP (U.S. Pharmacopeia) guidance cited:
- USP Chapter 795
- USP Chapter 1795 (as referenced for BUD default)

CNSP Lecture - Creams & Ointments (semi-solids)

Key takeaways