Ointments and Pastes Notes

Ointments and Pastes

Learning Outcomes

  • Explain the difference between ointments, creams, pastes, and gels.
  • Describe different ointment bases.
  • Describe methods for preparing ointment bases.
  • Discuss factors to consider when selecting an appropriate ointment base.
  • Discuss other ingredients in ointments.

Ointments

  • Ointments serve various purposes:
    • Antibiotics for skin infections.
    • Lubrication for dry eyes.
    • Delivery of corticosteroids for skin inflammation.
    • Protectant and moisturizing effects.

Ointments, Creams, Pastes, and Gels

  • Ointments: Semisolid formulations, may contain medicaments, with very little (if any) water.
  • Creams: Semi-solid formulations, either oil-in-water (o/w) or water-in-oil (w/o) emulsions, with a much larger percentage of water.
  • Gels: Semi-solid systems with a dispersion of small or large molecules, usually in an aqueous vehicle.
  • Pastes: Semisolid, generally contain a large proportion of solid material (e.g., 25%) compared to ointments; stiffer.
    • Pastes are used to protect the skin, absorb exudates, and remain in place after application. They are not typically used on hairy parts of the body.

Types of Bases

Bases used in the formulation of ointments and pastes:

  • Hydrocarbon or oleaginous bases
  • Absorption bases
  • Water miscible/water removable bases
  • Water-soluble bases

Hydrocarbon/Oleaginous Bases

  • Applied to the skin for emollient effect.

  • Protect against moisture escape, acting as effective occlusive dressings.

  • Remain on the skin for a long period of time.

  • Difficult to wash off.

  • Only a small amount of water can be incorporated.

  • Mineral oil is used as a levigating agent for powders.

  • Hard paraffin

    • A mixture of solid saturated hydrocarbons derived from petroleum or shale oil.
    • Melting point: 47-65^\circ C
    • Used to enhance the rheological properties of ointment bases.

  • White/yellow soft paraffin

    • A mix of semisolid hydrocarbons prepared from petroleum.
    • Melting point: between 38-60^\\circ C
    • White soft paraffin (WSP) is bleached yellow soft paraffin.

  • Liquid paraffin (mineral oil)

    • Mix of saturated aliphatic and cyclic hydrocarbons refined from petroleum.
    • Usually formulated with WSP/yellow soft paraffin to achieve the required viscosity.

  • Microcrystalline wax

    • Solid mix of saturated alkanes with a defined range of carbon chain lengths.
    • Used to enhance the viscosity of ointments (and creams).
    • Provides greater stability to formulations containing liquid paraffin (reduced bleeding of liquid component).

Absorption Bases

  • Used as emollients.

  • Do not provide the same occlusion as hydrocarbon bases.

  • Not easily removed from the skin with water washing, as the external phase is oleaginous.

  • Spreading is more favorable than oleaginous bases.

  • Typically contain one or more paraffins and a sterol base emulsifier (e.g., lanolin (wool fat), lanolin alcohols (wool alcohols), beeswax (white or yellow)).

  • Absorption bases generally result in better skin penetration by drugs than oleaginous bases.

  • Hydrophilic Petrolatum:

    • Cholesterol: 30g
    • Stearyl alcohol: 30g
    • White wax: 80g
    • White petrolatum: 860g
    • Allows incorporation of water to form a w/o emulsion.

  • Lanolin:

    • Wool fat, wax-like and derived from sheep’s wool.
    • Mixed with vegetable oils or paraffins to produce an ointment base.
    • Can absorb about twice its own weight of water to produce a w/o emulsion.
    • Usual concentration range used: 5-10\% w/w

  • Wool alcohols or Lanolin alcohols

    • Crude mix of sterols and triterpene alcohols, containing at least 30% cholesterol and 10-13% isocholesterol.
    • Added to mixes of paraffins (hard, white/yellow soft).
    • Including 5% w/w results in a 300% increase in the concentration of water that can be added into paraffin bases.

  • Beeswax:

    • Esters of aliphatic alcohols and linear aliphatic acids.
    • White beeswax = bleached yellow beeswax.

Water Washable/Removable Ointments

  • Used to form o/w emulsions.

  • Advantages:

    • Ability to accommodate large volumes of water.
    • Not occlusive.
    • Easily washed from the skin, clothing, and hair.
    • Aesthetically pleasing.

  • Examples:

    • Emulsifying ointment
    • Cetrimide emulsifying ointment
    • Cetomacrogol emulsifying ointment
      • Each of these contains liquid paraffin 20% w/w, WSP 50% w/w with either anionic, cationic, or nonionic emulsifying wax 30% w/w.
        • Anionic: Cetostearyl alcohol 90g, Sodium lauryl sulfate 10g, Purified water 4mL
        • Cationic: cetostearyl alcohol 900g and cetimide 100g
        • Nonionic: cetostearyl alcohol 800g and cetomacrogol 200g

Water-Soluble Bases

  • Hydrophilic, not hydrophobic.
  • Water-soluble components.
  • Non-greasy and easily removed by washing.
  • Miscible with exudates from inflamed sites.
  • Generally compatible with the vast majority of drugs.
  • Prepared by mixing different MW PEGs to the required consistency.
  • Main disadvantage is the inability to incorporate large volumes of aqueous solution as they soften and dissolve.

Selecting an Ointment Base

  • Desired release rate of the drug from the base.
  • Desired topical or percutaneous absorption.
  • Stability of the drug in the ointment base.
  • Desirability of occlusion of moisture from the skin.
  • Effect, if any, of the drug on the consistency or other features of the base.
  • Desire for the base to be easily removed by washing with water.
  • Characteristics of the surface to which it is to be applied.

Preparing Ointments

Methods:

  • Incorporation
  • Fusion
    • The method primarily depends on the nature of the ingredients.

Incorporation

  • Mix components until uniform.
  • Small scale: mortar and pestle or ointment slab and spatula.
  • Some compounding pharmacies have an “Unguator.”

Incorporation of Solids

Levigation

  • If necessary, reduce solids to a fine powder and blend in a mortar to avoid a gritty product.
  • Mix the solid material in a vehicle (levigating agent, e.g., mineral oil and glycerin) in which it is insoluble to make a smooth dispersion.
    • Generally, use the same volume of levigating agent as the solid material.
    • The levigating agent must be compatible with the ointment base.
  • The levigated powder mixture is then incorporated into the ointment base.

Pulverization by Intervention

  • Used for gummy noncrystalline materials (e.g., Camphor).
  • Dissolve material in a small amount of volatile solvent.
  • Pour the solution onto an ointment slab and allow the solvent to evaporate, leaving a thin film of solid material.
  • Spread ointment components onto the film to incorporate.

Incorporation of Liquids

  • Requires consideration of base properties to absorb the liquid.
  • All bases have limits to the quantity of liquid they can incorporate.
  • Alcoholic solutions of small volume may be easily added to oleaginous bases.
  • Natural balsams (Peru Balsam) mixed with castor oil, which reduces surface tension and allows more uniform dispersion through the base.

Fusion

  • Components are combined by melting together.
  • Stir until cool.
  • Heat-labile and volatile components are added last when the temperature is low enough not to cause decomposition or volatilization.
  • Medicated ointments containing beeswax, paraffins, stearyl alcohol, and high MW PEGs which do not lend themselves to incorporation are prepared by fusion.

Other Ingredients

  • Antioxidants
    • If the drug or base oxidizes, add an antioxidant.
    • Oil-soluble antioxidants: butylated hydroxytoluene, butylated hydroxyanisole, propyl gallate.
  • Absorption enhancers
    • Facilitate the passage of the drug through the skin.
    • Examples: alcohols, fatty alcohols and acids, polyols, pyrrolidines, surfactants, bile acids, amides such as urea and dimethyl formamide.

Example

  • Diprosone OV ointment

    • Betamethasone dipropionate
    • Optimized vehicle with propylene glycol, WSP, white beeswax, propylene glycol monostearate.
    • Propylene glycol increases penetration and enhances the local effectiveness of betamethasone.

  • Eulactol Heel Balm

    • Contains ingredients like urea, lanolin, petrolatum, decyl oleate, dicocoyl pentaerythrityl distearyl citrate, propylene glycol, microcrystalline wax, dimethicone, glyceryl oleate, carbomer, triethanolamine, aluminum stearate, methylparaben, propylparaben, butylparaben, ethylparaben, propyl gallate, citric acid, BHA; fragrance.

Other Excipients

  • Preservatives
    • Many ointments have no water and thus require no preservative.
  • Organic esters
    • Used to partly replace mineral oil.
    • Enhance spreadability.
    • Also enhance the dissolution of the drug in the ointment base.
    • Example: Isopropyl myristate.

Stability

  • Ointments are relatively stable.
  • If water is present, products are often less stable.
  • Physical stability and chemical stability
    • Physical stability: changes in appearance, odor, color
    • Chemical: degradation of drug or base ingredients
  • Ointments are best packed in tubes as there is minimal air space, and the product is kept cleaner during use.
  • Look for changes in physical attributes such as changes in consistency, separation of a liquid (bleeding), formation of granules or grittiness, and drying.

Pastes

  • Semisolids for external use.
  • Often contain finely powdered medication in WSP or liquid paraffin.
  • Very stiff.
  • Do not spread easily.
  • Localize drug delivery.
  • Important for corrosive materials such as dithranol, coal tar, salicylic acid.
  • Easier to apply a paste to a discrete lesion or plaque, retaining the integrity of the surrounding healthy skin.
  • Useful for absorbing harmful chemicals (e.g., ammonia) released when bacteria act on urine.
  • High powder content means they can absorb wound exudates.
  • A thick layer can act as a sun filter.
  • The principal use of pastes traditionally was as antiseptic, protective, and soothing dressings.
  • Often, before application, the paste was applied to lint and used as a dressing.

Examples

  • Compound Aluminum Paste BP
    • Aluminum powder: 200g
    • Zinc Oxide: 400g
    • Liquid Paraffin: 400g
    • Used to protect the skin and prevent maceration around colostomies and ileostomies.
  • Zinc and Coal Tar Paste BP
    • Zinc Oxide: 60g
    • Coal Tar: 60g
    • Emulsifying wax: 50g
    • Starch BP: 380g
    • Yellow soft paraffin: 450g
    • Used as an antipruritic preparation.

Compendial Requirements

Ointments and other semisolid dosage forms must meet USP tests for:

  • Microbial content
  • Minimum fill
  • Packaging
  • Storage
  • Labeling

Microbial Content

  • Ointments must meet acceptable standards for microbial content, and sterility is required for ophthalmic preparations.
  • Preparations which are prone to microbial growth must be preserved with antimicrobial preservatives (e.g., parabens, phenol, benzoic acid, sorbic acid, quaternary ammonium salts).
  • Good manufacturing practices limit microbial exposure.

Minimum Fill

  • USP’s minimum fill test involves the determination of the net weight or volume of the contents of filled containers to assure proper contents compared with the labeled amount.
  • Topical dermatologic semisolid products are packaged in jars (glass or plastic) or tubes (plastic or aluminum); Ophthalmic, nasal, vaginal, and rectal semisolid products are packaged in tubes.

Packaging, Storage, and Labeling

  • Packaged in a large mouth jar or metal or plastic tube.
  • Opaque or light resistant for light-sensitive products.
  • Store well closed in a cool place.
  • The label for certain products requires proper storage conditions, dosing, and administration.
  • In addition to the usual requirements, the USP directs that the labeling for certain ointments and creams include the type of base used (e.g., water-soluble or water-insoluble).

Additional Standards

  • In addition to the USP requirements, manufacturers often examine semisolid preparations for:
    • Viscosity
    • In vitro drug release to ensure intralot and lot-to-lot uniformity.