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Unformatted text preview: School of Pharmacy University of Wyoming Semisolid Dosage Forms
TOPICAL DOSAGE FORMS: Ointments, Creams, Pastes, Gels, Magmas & other
miscellaneous dosage forms Protect injured area from the environment & permit the skin to rejuvenate. Provide hydration, lubrication or produce an emollient effect (soothing and softening of the skin). Convey a medication to the skin or mucosa for a specific effect, either topically or systemically. Applied to the skin, eye, nose, vagina, and rectum. Topical dermatological products deliver drug into the skin (the target) to treat dermal disorders (topical absorption). Transdermal products deliver drugs through the skin (percutaneous absorption) to the general circulation for systemic effects (skin is not the target).
Drug penetration from SEMISOLID dosage forms depends on: The surface area covered The condition of the skin The base used The use of occlusive dressings The amount of pressure applied and the vigor with which it is rubbed. OINTMENTS (unguent = unguentum, Latin)
Def. Semisolid preparations for external application to the skin or mucous membranes. Soften or melt at body temperature Should spread easily Should not be gritty. Applications: usually used on dry, scaly lesions (oleaginous bases will keep drug on the skin
longer); formulated as topical, rectal and ophthalmic.
i. Non-medicated or ointment bases: white petrolatum, white ointment, hydrophilic
petrolatum, cold cream, hydrophilic ointment, PEG ointment, etc. ii. Medicated: with drug(s) Composition:
i. Active drug(s) ii. Stiffeners: waxes w/ high melting point (usually blended with oleaginous bases to
enhance viscosity) iii. Humectants: glycerin, propylene glycol, polyethylene glycol (PEG) 300 or 400, 70%
sorbitol (decrease evaporation rate of water) PHCY 6100/Teixeira 1 School of Pharmacy University of Wyoming Semisolid Dosage Forms
iv. Antioxidants: butylated hydroxyl toluene (BHT), ascorbic acid, sulfites, L-tocopherol
(delay the rate of rancidification) v. Penetration enhancers: increase rate of penetration through the skin. vi. Preservatives: benzoates, phenols, benzoic acid, parabens, quaternary ammonium salts
(prevent growth of Pseudomonas aeruginosa and Staphylococcus aureus_local
infection). vii. Oleaginous components viii. Aqueous components
ix. Emulsifying agents Preparation:
i. Selection of appropriate OINTMENT BASE Drug release rate Enhancement of percutaneous absorption Occlusion of moisture (“if skin is dry, wet it; if it is wet, dry it”) Stability of drug Influence of drug on other components of formulation (consistency) Patient factors (dry skin, intact or broken skin) Types of Ointment Bases
1. OLEAGINOUS or HYDROCARBON BASES (Epidermic) I. None or very little skin penetration
II. Insoluble in water
III. Not water washable
IV. Will not absorb water*
a. Petrolatum, USP, yellow petrolatum or petroleum jelly (VASELINE®)
b. White petrolatum, USP: decolorized petrolatum (White VASELINE®)
c. Yellow ointment, USP: yellow wax (from bee’s honeycomb) + petrolatum
d. White ointment, USP: white wax + white petrolatum
e. Liquid petrolatum or mineral oil, USP: levigating properties.
* Small volumes of aqueous solutions may be incorporated into an absorption base and then
mixed to the hydrocarbon base. PHCY 6100/Teixeira 2 School of Pharmacy University of Wyoming Semisolid Dosage Forms
2. ABSORPTION and EMULSION BASES (Endodermic-Diadermic): permit water incorporation or are water-in-oil (W/O) emulsions.
I. Fairly greasy but penetrate the skin (into and through)
II. Insoluble in water
III. Not easily water washable
IV. Anhydrous/contain water
V. Can absorb water
a. Hydrophilic petrolatum, USP: cholesterol + stearyl alcohol + white wax + white
petrolatum (permits the incorporation of small amounts of aqueous solutions forming
b. Aquaphor® and Aquabase®: allow incorporation of ~ 3 times its weight of aqueous
c. Lanolin, USP: contains 0.25% water; allows incorporation of ~ 2 times its weight of
aqueous solutions without separation. (emulsion base)
d. Cold cream, USP (emulsion base)
e. Hydrocream® (emulsion base)
f. Eucerin®, Nivea® (emulsion base)
3. WATER-REMOVABLE BASES: O/W emulsions = creams (diadermic) I. Penetrate into and through the skin
II. May be diluted with water
III. Water washable
IV. Will absorb water (serous discharge)
V. Contain water (external phase)
a. Hydrophilic ointment, USP: formula from USP 26/NF 21 (2003)
d. Unibase® PHCY 6100/Teixeira 3 School of Pharmacy University of Wyoming Semisolid Dosage Forms
4. WATER SOLUBLE BASES (Diadermic) I. Penetrate into and through broken skin
II. Water miscible: small amounts (softening)
III. Completely water washable (greaseless)
IV. Used for incorporation of solid substances
VII. Example: PEG ointment, USP
400 g polyethylene glycol 3350 (solid)
600 g polyethylene glycol 400 (liquid)
* Incorporation of aqueous solution will require substitution of 50 g PEG 3350 with equal
amount of stearyl alcohol.
Methods of Preparation: Incorporation of ingredients into commercially prepared bases: i. Manual ii. Mechanical Extemporaneous preparation: same principles used for preparing emulsions.
INCORPORATION: the components are mixed together until uniformity is attained.
a. Using Trituration or Spatulation (small scale) or roller mills (large scale)
b. Incorporation of SOLIDS:
(i) Trituration: mortar and pestle (ii) Spatulation: ointment slab (or parchment paper) + plastic or rubber spatula (iii) Rubbing the components together will uniformly mix them (friction). (iv) Initial reduction of particle size to reduce grittiness (levigating agent, e.g. mineral
oil, glycerin). (v) Solid substance to be added in very small quantity and does not have a different
color from other components: geometric method or dilution (vi) Alternatively: dissolved solid in small amounts of a solvent compatible with the
base and mix with the preparation. PHCY 6100/Teixeira 4 School of Pharmacy University of Wyoming Semisolid Dosage Forms
c. Incorporation of LIQUIDS:
(i) Should respect the limitations of each base and also the desired consistency of
final product. (ii) Alcoholic solutions: added to oleaginous and emulsion bases only if in very small
amounts. FUSION or “melting process”
a. Melting of ingredients together and cooling with constant stirring until congealing.
b. Trituration or spatulation after cooling: final uniform and smooth texture.
c. Useful for materials that melt but cannot be mixed by incorporation because they are
too thick or are provided as big pieces (e.g. beeswax, paraffin, high molecular weight
d. Solvent action is used when melting points of components are quite varied.
e. Heat-sensitive and volatile ingredients: added during cooling step (before congealing).
f. For emulsion-type ointments: melting process done before emulsification process
(i) oils and waxes are melted together (ii) aqueous solution containing heat-stable and water-soluble ingredients heated to
the same temperature as the oily ingredients (iii) aqueous solution is added slowly to the oily phase with constant stirring under
heat for ~ 5 min to prevent crystallization of waxes (iv) mixture is cooled with stirring until congealing. Compendial Requirements for ointments
i. Microbial content Not required to be sterile (exception, ophthalmics) Antimicrobial preservatives Preparation according to USP (Microbiological Attributes of Nonsterile Pharmaceutical
Products: rectal, urethral and vaginal should be tested for yeasts and molds) ii. Minimum fill Net weight or volume of contents = labeled amount iii. Packaging, Storage & Labeling Jars: clear or opaque plastic or glass; colored; sizes range from 0.5 oz-1 lb. Tubes: greater protection against external contamination and environmental conditions;
plastic or aluminum coated with epoxy resin, vinyl or lacquer; packaged with special
applicator tips; conventional continuous thread closure or tear-away tip; numerous
capacities available: 5, 15, 30g frequently used. PHCY 6100/Teixeira 5 School of Pharmacy University of Wyoming Semisolid Dosage Forms Syringes: compounded products. Temperatures < 30°C (RT, away from excessive heat) to prevent softening and
separation of phases. Appropriate labeling for the mode of administration. Stability/Additional standards
i. Viscosity: change in consistency, separation of a liquid, formation of granules or
grittiness, drying. Oleaginous, anhydrous bases: relatively stable. Emulsion bases: less stable Extemporaneous preparations with water: be conservative (dispense only a 2-week
supply) Extemporaneous nonaqueous liquids or anhydrous preparations from a manufactured
product: beyond-use date is 25% of the time remaining on the product’s expiration date
or 6 months, whichever is earlier. ii. In vitro drug release: within-lot and lot-to-lot uniformity. iii. Physical stability: appearance, feel, color, odor
Def. Opaque soft solids or thick liquids for external application.
i. Drugs are dissolved or suspended in w/o emulsion o/w emulsion or other waterwashable bases ii. Vanishing creams: o/w emulsion containing large % of water and stearic acid (water
evaporates leaving a thin film on skin). iii. Easier to spread and remove iv. Formulated as topical, rectal and vaginal. Applications: weeping or oozing lesions (“drying” effect_ body fluids will be miscible with
cream aqueous external phase).
Preparation: same as for preparation of emulsions.
Preservation: similar to ointments that contain water.
Packaging: tubes, jars, syringes, applicators (vaginal & rectal), pump dispensers.
Labeling: appropriate for the mode of administration.
Stability: same as ointments + emulsion breakage, crystal growth, shrinkage resulting from
water loss, gross microbial contamination. PHCY 6100/Teixeira 6 School of Pharmacy University of Wyoming Semisolid Dosage Forms
Def. Thick, stiff ointments that ordinarily do not flow at body temperature
i. Protectively coat the areas to which they are applied. ii. Usually contain at least 25% solids. Application
i. To areas that require protection ii. Preparation remains in place after application iii. Absorptive of serous secretions iv. Less greasy than some ointments v. Not suited for hairy parts of the body vi. Ex: Zinc oxide paste (Lassar’s paste) Preparation:
i. Fusion technique: heat improves the workability of base prior to incorporation of solids. ii. Use portion of base as levigating agent: if needed to render powdered component
smooth. iii. Must be cooled before placed in container. If too stiff and difficult to apply, reduce the
concentration of waxy components. Ch. 14- GELS and MAGMAS: colloidal dispersions
1. Definitions (USP23/NF18)
a) Gels are semisolid systems consisting of dispersions of small inorganic particles or large
organic molecules interpenetrated by a liquid. b) Gels are semirigid systems in which the movement of the dispersing medium is
restricted by an interlacing three-dimensional network of particles or solvated
macromolecules of the dispersed phase. 2. Excellent drug delivery systems: oral, topical, nasal, vaginal, rectal; compatible with many
3. Relatively easy to prepare and very efficacious
a) Imbibition: taking up of liquid with no measurable increase in volume. b) Swelling: taking up of liquid with increase in volume(solvation) c) Syneresis: intense interaction between particles of the dispersed phase so that, on
standing, the dispersion medium is squeezed out in droplets and the gel
shrinks=instability. d) Thixotropy: reversible gel-sol formation with no change in volume or temperature.
(sol=liquid form of a gel upon agitation) PHCY 6100/Teixeira 7 School of Pharmacy University of Wyoming Semisolid Dosage Forms
e) Xerogel: removal of the liquid from a gel, leaving only the framework- e.g. gelatin
sheets, acacia tears, tragacanth ribbons. 5. Characteristics
a) Gels may be clear as water; others are turbid (ingredients not completely molecularly
dispersed or dissolved, or presence of aggregates of dispersed phase= disperse light). b) Most gels are water washable, water- soluble, water absorbing and greaseless but
some have continuous phase alcoholic or oleaginous. c) Concentration of gelling agents: d) usually 0.5-2% (<10% of formulation)
Preservatives are recommended: sodium benzoate, benzalkonium chloride,
methylparaben, propylparaben 6. Single-phase systems: gels that contain linear or branched polymer macromolecules that
dissolve in water and have no apparent boundary with the dispersing medium.
a) Natural polymers (e.g. tragacanth) b) Semisynthetic cellulose derivatives (e.g. methylcellulose) c) Synthetic polymers (e.g. carbomer polymers) Mucilages: single-phase gels made from synthetic or natural macromolecules. 7. Two-phase systems: Gels that contain small, discrete particles Are thixotropic: semisolid on standing but liquid when shaken Ex: Aluminum hydroxide gel & Bentonite Magma, NF Called Magmas if have large particle size 8. Magmas (or Milk)
a) Are two-phase systems with large particle size or floccules of small, distinct particles. b) Ex: Bentonite Magma, NF 9. Common gelling agents
a) Acacia, pectin, starch, tragacanth, xanthan gum, etc b) Alginic acid (seaweed) c) Animal/vegetable fats: lard, cocoa butter d) Gelatin e) Bentonite, Veegum (magnesium aluminum silicate) f) Carboxymethylcellulose (CMC) & other cellulose deriv.(methylcellulose, sodiumcarboxymethylcellulose [CMC], Pluronic F-127) g) Carbomer resins (Carbopols®) h) Carbowax bases (PEG ointment) PHCY 6100/Teixeira 8 School of Pharmacy University of Wyoming Semisolid Dosage Forms
i) Colloidal silicon dioxide j) Polyvinyl alcohol (PVA) k) Petrolatum, mineral oil/polyethylene gel, plastibase (jelene) 10. PREPARATION: general guidelines
a) Active drug does not interfere with the gelling process: add it prior to gelling for
uniformly dispersion. b) Active drug interferes with gelling: place gel + active ingredient in a plastic bag, which is
"kneaded" to thoroughly mix the drug, then cut corner of bag and squeeze product into
final container. c) The continuous phase of most gels is usually aqueous but can also be alcoholic or
oleaginous. d) Gelling agents: usual concentration is 0.5-2%; in general sprinkled in small portions on
the surface of aqueous liquid. e) Heating/Cooling: hot water: bentonite, gelatin; cold water and heat: CMC, colloidal silicon dioxide, methylcellulose. f) Fastest dispersion is generally achieved by sprinkling slowly very small particles of
powder (through a sieve), into a rapid stirring liquid. g) Stirring/Sonication: most gelling agents disperse faster with rapid stirring or sonication
(exception= bentonite is added to non-agitated water). Sonication also removes air
bubbles. h) Glycerin, propylene glycol, alcohol or other wetting agent can be used to "pre-wet" the
gelling agent to prevent clumping. i) Neutralizer: thicken the gel after the gelling agent is dispersed Na hydroxide, K hydroxide for dispersions with <20% alcohol; triethanolamine if up to 50% alcohol; others: sodium carbonate, ammonia, borax. j) High water content: support growth of bacteria, mold, and fungi; use preservatives that do not affect the gelling agent's efficacy. OTHER TOPICAL DOSAGE FORMS
a) PLASTERS: adhesive masses spread on a backing of paper, fabric, moleskin or plastic.
i. Provide prolonged contact and effect at the site of application (skin). ii. Sized to fit surface to be covered PHCY 6100/Teixeira 9 School of Pharmacy University of Wyoming Semisolid Dosage Forms
iii. Ex: salicylic acid plaster for removal of corns on toes. b) GLYCEROGELATINS: plastic masses containing gelatin + glycerin + water + medicinal
i. Preparation is similar to gummy base for troches ii. Need to be warmed and melted before application (fine brush) iii. Covering of area with bandage iv. Ex: zinc gelatin for varicose ulcers c) TOPICAL SOLUTIONS
i. Solutes dissolved in aqueous/alcoholic vehicle. ii. Usually contain anti-infective agents iii. Ex: Povidone-Iodine Topical solution - Betadine®, Thimerosal topical solution Merthiolate®. d) TINCTURES: solutes dissolved in alcoholic or hydroalcoholic vehicle. Usually contain antiinfective agents. Ex: Iodine tincture, USP.
e) OTHER MISCELLANEOUS TOPICAL PREPARATIONS: Powders, Aerosols, Rubbing
IMPORTANT INFORMATION ABOUT ALL TOPICAL DOSAGE FORMS: All medication intended for topical use should have “For external use only” on its label.
The pharmacist should also explain/demonstrate clearly the mode of administration and
route, if a specialized tool is used for administration (vaginal and rectal applicators).
Necessity of a bandage or covering should be according to physician’s prescription and if
not stated, the wound should be medicated and left open to the atmosphere whenever
possible (exception of corticosteroid drug).
Ointments, creams, pastes and lotions should not be substituted one for another by a
pharmacist without the consent of the prescribing physician. PHCY 6100/Teixeira 10 ...
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This note was uploaded on 10/15/2010 for the course PHCY 6100 taught by Professor Teixeira during the Fall '10 term at Wyoming.
- Fall '10