Topical delivery dosage forms

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Topical delivery dosage forms

• Ointments
• Definition and applications
• Classification
• Hydrocarbon bases
• Absorption bases
• Water-removable bases
• Water-soluble bases
• Selection of ointment bases
• Preparation of ointments
• Some requirements for ointments
• Other dosage forms cream, gel/jelly, paste

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Ointments

• Ointments are semi-solid preparations intended
  for external use. They are easily spread.
• Typically used as
• Emollients to make skin more pliable
• Protective barriers
• Vehicles in which to incorporate medication

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Ointment bases

• Hydrocarbon
• Absorption bases
• Water-removable bases
• Water-soluble bases

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Hydrocarbon bases

• Petrolatum, USP
• Yellow petrolatum/petrolatum jelly
• Vaseline (Chesebrough-Ponds/Unilever)
  (vahser-elaion)
• Melts at 38-60oC
• White petrolatum, USP
• Decolored petrolatum,
• White petroleum jelly/white vaseline
• Yellow ointment, USP
• Yellow wax (5, w/w), petrolatum (95)
• White ointment, USP
• White wax/white petrolatum

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Mineral oil

• Liquid petrolatum
• Is a mixture of refined liquid saturated
  hydrocarbons obtained from petroleum
• Levigating agent to incorporate lipiphilic solids
• An excipient in topical formulations where its
  emollient properties are exploited as an
  ingredient in ointment bases.

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Oleaginous bases

• 1. Synthetic esters
• glyceryl monostearate, isopropyl myristate,
  isopropyl palmitate, butyl stearate, butyl
  palmitate, and long-chain alcohol (cetyl alcohol,
  stearyl alcohol, PEG)
• 2. Lanolin derivates
• Lanolin oil, hydrogenated lanolin

Comprehensive Pharmacy Review, 5th ed., by
Shargel et al.
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Hydrocarbon bases

• Oleaginous bases
• Emollient effect hydrates skin due to sweat
  accumulation
• Occlusive dressing
• Difficult to wash-off/remove
• Small amount of water can be incorporated into it
  with difficulty and can be protective to water
  labile drugs such as tetracycline and bacitracin.
• Is greasy and can stain clothing.

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Occlusive and skin hydration
From S. Hoag, U Maryland
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Absorption bases

• Those that permit the incorporation of aqueous
  solution resulting in he formation of w/o
  emulsions
• --hydrophilic petrolatum, USP
• Cholesterol 30 g, Stearyl alcohol 30 g
• White wax 80 g, White petrolatum 860 g
• --Aquaphor A gentle healing ointment to help
  heal dry, cracked skin
• (Petrolatum. Other Ingredients Mineral
  Oil, Ceresin, Lanolin Alcohol, Panthenol,
  Glycerin, Bisabolol)
• Those that are w/o emulsion
• Hydrous lanolin w/o emulsion containing 25
  of water
• lanolin USP Anhydrous, contains lt 0.25 of
  water, absorbs twice its weight in water, also
  called wool wax, wool fat, or wool grease, a
  greasy yellow substance from wool-bearing
  animals, acts as a skin ointment, water-proofing
  wax, and raw material (such as in shoe polish).

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Properties of absorption bases

• Absorption bases (anhydrous)
• Emollient
• Occlusive
• Absorbs water
• Greasy
• W/O emulsion
• Emollient
• Occlusive
• Contains water, absorbs additional water
• Greasy

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Water-removable bases

• Water-washable bases, O/W emulsion
• Hydrophilic ointment, USP
• Methylparaben 0.25 g
• Propylparaben 0.15
• SDS 10
• Propylene alcohol 120
• Stearyl alcohol 250
• White petrolatum 250
• Water 370
• Vanishing cream o/w emulsion contains la large
  of water and humectant. An excess of stearic acid
  in the formula helps to form a thin film when the
  water evaporates.
• Dermovan a hypoallergenic, greaseless emulsion
• Unibase non-greasy emulsion base has pH close to
  that of skin

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Properties of water-removable bases

• Water-washable, easier to remove
• Non/less greasy
• Can be diluted with water
• Non/less occlusive
• Better cosmetic appearance
• Better compliance

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Water-soluble bases

• PEG ointment, NF
• - PEG 3350 400 g, PEG 400 600 g
• - Polyethylene glycol 200, 300, 400
  (4-8oC), 600 (20- 25oC), 1000, 1450, 3350,
  4000, 6000, 8000 and 20000
• - Only a small amount of liquid (lt5) can
  be incorporated
• - If 6-25 of liquid is to be incorporated,
  50 g of the 400 g of PEG 3350 may be replaced
  with stearyl alcohol
• Examples
• ZOVIRAX, (acyclovir), GSK, Ointment 5
• BACTROBAN SmithKline Beecham Mupirocin
  Topical Antibiotic (Each g of ointment contains
  mupirocin 20 mg (2) in a bland water-soluble
  ointment base consisting of PEG 400 and PEG 3 350
  (PEG ointment, USP).

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Water-soluble bases

• Glyceryl monstearate
• polyhdric alcohol esters
• wildly used in cosmetic and ointment bases
• Cellulose derivatives
• Methylcellulose
• Cellulose
• Hydroxyethyl cellulose
• Carbopol/carbomer
• synthetic high MW polymers of acrylic acid
  cross-linked with either allysucrose or allyl
  ethers of pentaerythritol.

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Properties of water-soluble bases

• Water soluble and washable
• Non-greasy
• Non/less occlusive
• Lipid free
• Synthetic base
• Relatively inert
• Does not support mold growth
• Little hydrolysis, stable
• May dehydrate skin and hinder percutaneous
  absorption.

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Selection of the appropriate base

• Desired release rate of drug substance
• Desirability for topical or percutaneous
  absorption
• Desirability of occlusion
• Stability of drug in ointment
• Effect of drug on ointment base
• Desire for easy removable

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Preparation of ointments

• Incorporation components are mixed until a
  uniform preparation is attained.
• -- Incorporation of solid
• -- Incorporation of liquid
• Fusion All or some components are combined by
  being melted together and cooled with constant
  stirring until congealed.
• -- High melting temperature bases such as
  beewax, paraffin, stearyl alcohol, and high Mw
  PEG.
• Ointments having emulsion bases usually involve
  melting and emulsification steps.

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Incorporation

• A spatula with a long, broad blade should be used
• Insoluble substances should be powdered finely in
  a mortar and mixed with an equal amount of base
  until a smooth mixture is obtained. The rest of
  the base is added in increment.
• Levigation of powders into small portion of base
  is facilitated by the use of levigating agents.
• Levigating agents
• Mineral oil for oily bases or bases where oil
  are the external phase
• Glycerin for bases where water is the
  external phase.
• Levigating agent should be equal in volume
  to the solid material.
• When liquid is added into an ointment, care must
  be taken to consider the capacity of the ointment
  in accepting the liquid. When it is necessary to
  add an aqueous preparation to a hydrophobic base,
  the solution should be added into minimal amount
  of the hydrophilic base first. The mixture should
  be then added into the hydrophobic base.

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Example

• Medication order
• Sulfur (3-6, usually)
• Salicylic acid, 600 mg
• White petrolatum, 30 g
• The particle sizes of sulfur and salicylic
  acid are reduced separately in a mortar and then
  blended together. The powder mixture is then
  levigated with the base using geometric dilution.

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Fusion

• Used when the base contains solids that have
  higher melting points. Also for solid medications
  that are readily soluble in melted bases.
• The oil phase should be melted separately,
  starting with materials having the highest
  melting point.
• The ingredients in the water phase are combined
  and heated separately to temperature equal to
  above that of the oil phase
• The two phases are them combined. If a w/o system
  is desired, the hot aqueous phase is incorporated
  into the hot oil phase with agitation.
• Volatile materials are added after the melted
  mixture cools to desired temperature.

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Requirement for ointments

• Microbial content do not need to be sterile, but
  must meet the FDA requirement of the test for
  absence of bacteria such as S. areus and P.
  aeruginosa for dermatological products.
• Minimum fill
• Packaging, storage, labeling (label should
  include the type of base used)
• Additional standards viscosity, in vitro release

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Topical dosage form

• Ointments
• Creams
• Pastes
• Gels/jellies
• Solution
• Plasters
• Aerosols
• Powders

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Cream

• Semisolid preparations containing one or more
  medicinal agents dissolved in either an o/w or
  w/o emulsion or in another type of water-washable
  base.
• Vanishing cream o/w with high of water and
  stearic acid.
• Cold cream (an emulsion for softening and
  cleansing the skin) w/o, white wax, spermaceti,
  almond oil, sodium borate.

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Cream

• Typically of low viscosity, two phase system (w/o
  or o/w)
• Appears creamy white due to the scattering of
  light.
• Traditionally, it is the w/o cold cream
• Currently and most commonly, it is the o/w
  emulsion.

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Cold cream

• w/o emulsion frequently using a borax-beewax
  combination as the emulsifying agent and mineral
  oil or vegetable oil as the oily phase. A
  protective film remains on the skin following the
  evaporation of the water. The slow evaporation of
  water gives the skin a cooling effect.
• To prepare, melt white wax, spermaceti, and
  almond oil together, adding host aqueous solution
  of sodium borate, and stir until the mixture is
  cool.
• A formula
• Water, 34.6, Borax, 1, methylparaben, 0.25
• Light mineral oil, 50, synthetic beewax,
  13, Glyceryl monostearate, 1, propylparaben,
  0.15.

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Creams as drug delivery systems

• Good patient acceptance
• Water evaporation concentrates drug on skin
  surface
• Must avoid drug crystallization
• Can add co-solvents such as propylene glycol

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Gels and jellies

• Jellies are water soluble bases prepared from
  natural gums such as tragcanth, pectin,
  alginates, boroglycerin, or from synthetic
  derivatives of natural substances such as
  methylcellulose and NaCMC.
• Gels semisolids consisting of dispersions of
  small or large molecules in an aqueous liquid
  vehicle rendered jelly-like through the addition
  of a gelling agent.
• Single-phase gel
• Carbomers high Mw water soluble polymers of
  acrylic acid cross-linked with allyl ethers of
  sucrose or pentaerythritol.
• Two-phase system magma/milk of
  magnesia/magnesia magma, a gelatinous precipate
  of magnesium hydroxide

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Pastes

• Semisolid contains a larger proportion of solid
  materials than ointments.
• Stiffer than ointment
• Good protective barriers
• Opague, water impermeable, prevent
  dehydration
• Good absorbent

Lassers plain zinc paste Zinc oxide 25
Starch, 25 White petrolatum, 50 Anthralin
in for psoriasis
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