Compounding Topicals Notes

Compounding Topicals

Learning Objectives

• Examine significant considerations in formulating topically applied compounded preparations (CPs).
• Demonstrate clinical applications of topically applied CPs.
• Discuss examples of commonly used compounded preparations, formulation design, and their clinical value.
• Discuss highlights of a patient consultation.

Definitions

• Traditional Definitions:
  • Ointment: Semisolid preparations for external application to skin or mucous membranes.
  • Cream: Semisolid dosage forms containing one or more drug substances in a suitable base.
  • Issue: The word "ointment" is used generally for any semisolid dosage form.
• Revised Definitions:
  • Ointment: A viscous oleaginous or polymeric semisolid dosage form.
    • Primarily drug substances incorporated into hydrocarbon bases.
  • Cream: A dosage form comprising a viscous semisolid emulsion.
    • Primarily oil-in-water (o/w) emulsion bases but can apply to any semisolid emulsion.

Topical vs. Transdermal

• USP Definition: Application to the outer surface of the body.
• Topical:
  • Ointments, creams, and gels deliver an API to the skin (target organ).
• Transdermal:
  • Ointments, creams, and gels deliver an API into circulation (target).

Example of Transdermal Route

• Ketoprofen 200mg/ml cream.
• Benefits:
  • Avoids the oral route of administration.
  • Less concern about a history of gastric ulcers.
  • Direct application.
  • Avoids first-pass metabolism.
  • Ability to include other agents (e.g., lidocaine for further pain relief).
  • Extended delivery time.
  • Overcomes short half-life of the drug.

Characteristics: Ointments

• Semisolid.
• Intended for external use (including mucous membranes).
• May melt at body temperature.
• Spreads easily (less messy).

Characteristics: Creams

• Opaque, soft solids or thick liquids.
• Intended for external use.
• Medication suspended within the cream.
• Can be with or without emulsion.
• Made to vanish or disappear.
• May contain penetration enhancers.

Characteristics: Gels

• Clear or opaque, gelatinous.
• Semisolid.
• Versatile delivery system.
• Can contain penetration enhancers.
• Inorganic or organic gel types.
• Broadly compatible with APIs.

Formulation Considerations

• Condition(s) being treated.
• Whether and how much skin penetration is needed.
• Characteristics of the skin on the desired location.
• Dose needed for the condition being treated.
• Compatibility with active ingredient(s).
• Option of using penetration enhancers.
• Skin type of the individual (e.g., facial skin).

Skin Types and Suitable Preparations

Semisolid Bases

• Hydrocarbon (Oleaginous): White Petrolatum, White Ointment, Vaseline
• Anhydrous Absorption: Lanolin, Aquaphor
• Water-in-Oil Emulsion Absorption: Cold Cream, Eucerin, Nivea
• Oil-in-Water Emulsion (Hydrophilic Ointment): Dermabase, Velvachol

Semisolid Base Characteristics

Choice of Semisolid Base

• To provide a vehicle for applying medication for local or systemic effect.
• Depends on:
  • Nature of the incorporated medication (bioavailability, stability, compatibility).
  • Action or effect desired of the base (emollient, protective, occlusive).
  • Area of application (practical considerations).
• If a prescription specifies a particular semisolid base and a change is needed for compatibility or stability, the prescriber should be consulted.

Cream Base Charts (Manufacturer Specific)

• Examples of commercially available cream bases with details on appearance, description, dermatological use, cosmetic use, vaginal use, stability, API compatibility, salt tolerance, API carrying capacity and penetrating capabilities were provided for:
  • VersaPro™ Cream Base.
  • VersaPro™ Lotion Base.
  • HRT Cream Base (Women).
  • Transdermal Pain Base.
  • PLO Transdermal Cream.
  • PenDerm™ Cream Base.
  • Lipo Cream Base.

Gel Base Charts (Manufacturer Specific)

• Examples of commercially available aqueous and anhydrous gel bases with details on appearance, description, dermatological use, cosmetic use, vaginal use, stability, API compatibility, salt tolerance, API carrying capacity were provided for:
  • NovaFilm™ Gel Base
  • VersaPro™ Gel Base
  • HRT Gel Base (Men)
  • PLO Gel MediFlo™ 30
  • VersaPro™ Anhydrous Base
  • OleaBase™ Plasticized
  • AlpaWash
  • CopaSil

Compounding Goals

• Homogenous (well blended).
  • Equipment:
    • Ointment slabs or large parchment paper/pads.
    • Spatulas (metal, rubber).
    • Ointment Mill:
      • Advantages: Homogenization and Particle size reduction.
      • Rolls formulation between three ceramic rollers.
      • Gap and speed adjustments.

Compounding Goals

• Levigating Agent:
  • Mineral Oil: for hydrocarbon, anhydrous absorption, or water-in-oil emulsion base.
  • Glycerin: for oil-in-water emulsion or water-soluble base.
• Quantity to Prepare:
  • Loss is common; prepare a 10% excess (follow Master Formulation reference).
• Packaging:
  • Dress ointment to give a “finished” appearance and avoid getting the product on the lid.

Compounding Procedure - Levigation

• Smooth and non-gritty - Fine particle size.
  • Drug selection and Trituration.
• Levigation:
  • Process of reducing particle size of a solid by triturating it with a small amount of liquid or melted base in which the solid is not soluble.
  • Facilitates incorporation of solids into bases.
  • If possible, use an ingredient to levigate; otherwise, use an auxiliary agent.

Levigating Agents

• If the formulation already contains an ingredient that can function as a levigating agent, that liquid should be used.
  • Melted ointment base may also be used.
• Auxiliary Levigating Agent Selection:
  • Agent must be chemically similar and/or compatible with the base you are using.
  • If dealing with emulsion bases, the levigating agent should be compatible with the external phase.
    • Hydrocarbon, anhydrous absorption bases, and w/o emulsions – use Mineral Oil.
    • o/w emulsion and water-soluble bases – use Glycerin.

Levigating Agents - Quantity

• General Rule: Unless the volume is specified in the prescription, use the minimum amount necessary to lubricate (wet) the solids.
• Factors determining the amount needed:
  • The quantity and properties of the solids to be incorporated.
  • The properties of the ointment base.
• Important not to use too much!
  • May change properties of the base (e.g., change the desired spreading consistency or crack an emulsion base).
  • Keep track and record volume used.

Selecting a Levigating Agent

Weights of Levigating Agents

• Need to account for the weight of the levigating agent used.
• The amount of levigating agent used should be measured in a syringe or graduate.
• The weight of the levigating agent that is used should be calculated from the volume incorporated using the agent's specific gravity.
• There should be a corresponding decrease in the weight of the ointment base to bring the preparation to the desired final weight.

Specific Gravity of Common Levigating Agents

Example Levigation Calculation

• Zinc Oxide 10% in Polysorb, 30 g
  • Calculate for 10% excess = 30 g * 1.10 = 33 g
  • Required amount of Zinc Oxide = 33 g * 0.10 = 3.3 g
  • Levigating Agent to use = Mineral Oil
  • Volume of Levigating Agent used = 2 ml
  • Weight of Levigating Agent = 2 mL * 0.88 g/mL = 1.76 g
  • Required amount of Polysorb = 33 g – 3.3 g – 1.76 g = 27.94 g
• Zinc Oxide 10% in Velvachol, 30 g
  • Calculate for 10% excess = 30 g * 1.10 = 33 g
  • Required amount of Zinc Oxide = 33 g * 0.10 = 3.3 g
  • Levigating Agent to use = Glycerin
  • Volume of Levigating Agent used= 1.5 ml
  • Weight of Levigating Agent = 1.5 mL * 1.26 g/mL = 1.89 g
  • Required amount of Velvachol = 33 g – 3.3 g – 1.89 g = 27.81 g

Incorporation of Liquids

• Formulations that include liquids require semisolid bases that will absorb the liquid.
• The prescriber should be consulted about base changes.
• Use care when incorporating water or alcohol.
  • They have a low surface tension and can splash.
  • They soak into the paper of ointment pads. Ointment slabs are the preferred equipment for these preparations.
• Semisolid bases do not immediately absorb liquid; the liquid must be carefully spatulated into the base.

Example Master Formulations

• Examples of Master Formulations were provided for:
  • Diltiazem Hydrochloride 2% Rectal Ointment (Suspension, 100 g)
  • Each master formula includes:
    • A suggested formula.
    • Ingredient listing with quantities, units, NDC #, supplier, lot number, and expiry date.
    • Special preparatory considerations.
    • Suggested presentation with packaging requirements, auxiliary labels and pharmacist/patient instructions.

Topical Preparation Guidelines

• Interpret the Prescription
• Review additional information
• Review Ingredients (Master Formulation Record)
• Complete calculations & DOUBLE CHECK
• Complete the Compounding Worksheet and Perform Procedure
• Perform quality control, package into an appropriate container, label

Preparation Guidelines

• Beyond Use Dating (BUD)
  • Stability:
    • Physical
    • Chemical
    • Microbiological
  • In the absence of stability information, use USP chapter 795 recommendation:
    • “For Water-Containing Topical/Dermal and Mucosal Liquid and Semisolid Formulations - The BUD is not later than 30 Days.”

Preparation Guidelines - Packaging

• Container types: tubes, jars, applicators, syringes, patches, and pump dispensers.
• Match container to route of administration or product characteristics.
• Ointment Jar:
  • Remove air pockets by tapping the container.
  • Dress ointment to give a “finished” appearance.
  • Avoid getting the product on the lid.

Preparation Guidelines - Quality Control & Labeling

• Quality Control:
  • Check and document the following on the compounding record: final weight, visual appearance, color, odor, viscosity, and texture.
• Labeling:
  • Name of all active drugs and amount expressed as percent w/w (%) concentration, e.g., “Zinc Oxide 10%, Calamine 5%”.
  • Name of commercial base used, e.g., “in Eucerin”.
  • Name of route, e.g., Topical, rectal, vaginal, etc.
  • Name of dosage form, e.g., cream, ointment, paste, etc.
  • Example: “Zinc Oxide 10%, Calamine 5% in Eucerin Topical Cream”
• Auxiliary Labels:
  • Include common auxiliary labels such as “For External Use Only” and “Keep away from Children”.
• Storage:
  • Refer to Master Formulation and other references.

Patient Consultation

Patient Consultation must include at least the following (must review all other possible side effects of API):

• Apply only to the affected area
• Use a measuring spoon to estimate dose (depending on the CP)
• Wash hands after rubbing in until dissolved
• May absorb into the skin over 3-4 hours
• Do not apply with any other medications or after a long, hot shower or vigorous exercise
• Report any sensitivity reactions to your prescribing doctor or pharmacist
• Refer to Master Formulation sheet for CP-specific instructions