Semisolid dosage forms and rheology Flashcards
Overview of semi solid dosage forms
Ointments, creams and gels are semisolid dosage forms intended
for topical application
• May be applied to skin, placed on the surface of the eye, used
nasally, vaginally or rectally
• Most used for the effects of the therapeutic agents they contain;
unmedicated ones are used as protectants or lubricants
• Topical applications can be used for local or systemic effects
Ointments
Semisolid preparation intended for external application to skin or
mucous membranes
• May be medicated or not
• Ointment bases may be used for their physical effects or as vehicles
for medicated ointments
Ointment bases
- Oleaginous
- Absorption
- Water-removable
- Water-soluble
Oleaginous (or hydrocarbon) bases
On application to skin, have an emollient effect, protect against
escape of moisture, effective as occlusive dressings, can remain on
the skin for long periods without drying out, and are difficult to wash
off due to their immiscibility with water
Levigation
commonly used to reduce particle size and grittiness of added powders
Oleaginous bases, when powder substances are to be incorporated
mineral oil may be
used as the levigating agent
Oleaginous bases examples
Petrolatum, USP - yellow petroleum and petroleum jelly ( vaseline)
White petrolatum- petroleum jelly ( white vaseline)
Yellow ointment- simple ointment
White ointment
Petrolatum, USP – Also known as (AKA), yellow petrolatum and petroleum jelly
Purified mixture of semisolid hydrocarbons obtained from petroleum
– Unctuous mass, varying in color from yellowish to light amber
– Melts at 38-60 C
– Can be used alone or in combination with other agents as an ointment base
– Example: Vaseline
White petrolatum, USP – AKA, petroleum jelly
Purified mixture of semisolid hydrocarbons from petroleum
– Wholly or nearly decolorized
– Considered more esthetically pleasing by some
– Example: White Vaseline
Yellow ointment, USP – AKA, simple ointment
1000 g contains: 50 g yellow wax and 950 g petrolatum
– Has a slightly greater viscosity than plain petrolatum
White ointment, USP
1000 g contains: 50 g white wax (bleached yellow wax) and 950 g white petrolatum
Yellow and white ointments are prepared by
melting the wax component, adding the
petrolatum until mixture is uniform, then cooling and stirring until congealed
Absorption bases
May be used as emollients
- are not easily removed from the skin because external phase is oleaginous, and are useful as pharmaceutical adjuncts to incorporate small volumes of aqueous
solutions into hydrocarbon bases
Two types of absorption bases
A. Those that permit incorporation of aqueous solutions resulting in water-in-oil emulsions (W/O)* (called Anhydrous)
B. Those that are water-in-oil (W/O) emulsions that permit incorporation of additional quantities of aqueous solutions
*Emulsions are
disperse systems where a liquid is dispersed in an external liquid phase
Absorption bases examples
- Hydrophilic petrolatum, USP
- Lanolin, USP – AKA, anhydrous lanolin
- Hydrophilic petrolatum, USP
Type A absorption base
- Stearyl alcohol and white wax are melted, cholesterol added with stirring until
dissolved, white petrolatum added, then cooled while stirring until congealed
– Aquaphor is a variation of hydrophilic petrolatum
Lanolin, USP – AKA, anhydrous lanolin
Type B absorption base
– Obtained from wool of sheep
– Wax-like substance that has been cleaned, deodorized and decolorized
– Contains no more than 0.25% water; additional water may be incorporated by
mixing
Water-removable bases
Oil-in-water (O/W) emulsions resembling creams
– External phase is aqueous
-More easily washed from skin, may be diluted with water or aqueous
solutions, and can absorb serous discharges
Water-removable bases example
Hydrophilic ointment, USP
-Stearyl alcohol and white petrolatum are melted together at ~75 C; the
other agents, dissolved in the purified water, are added with stirring until
mixture congeals
Water-soluble bases
Do NOT contain oleaginous components
- are completely water
washable and often referred to as greaseless
- Soften greatly with water, large amounts of aqueous solutions not
effectively incorporated
• Mostly used for incorporation of solid substances
Water-soluble base example
Polyethylene glycol ointment, NF
Numeric designations associated with PEGs refer to average molecular
weight of the polymer
• Viscosity increases with molecular weight
• <600 – Clear, colorless liquids
• 600-1000 – Semisolids
• >1000 – White, wax-like
Selection of the appropriate
base
• Depends on number of factors, including
- Desired release rate of drug substance from base
- Desirability of topical or percutaneous drug absorption
- Desirability of occlusion of moisture from skin
- Stability of drug in the base
- Effect, if any, of the drug on consistency or other features of the
base - Desire for a base easily removed by washing with water
- Characteristics of the surface to which it is applied
Effect of ointment bases on drug release
The partition of a water-insoluble (lipophilic) drug into the skin may decrease in an oleaginous phase due to the drug’s affinity toward the formulation
Lipophilic drug release can be significantly increased when
the ointment base shows
an increased water affinity
When would you recommend water-soluble and water-removable bases
- rapid release of lipophilic drugs
-also useful for drugs that undergo hydrolytic degradations,
as formulations can be made that contain no water
For hydrophilic drugs, absorption bases
(anhydrous and W/O emulsion systems) can
provide greater drug release rates, as the base has low affinity for the drug and also
absorbs water, allowing easier passage of the drug through the ointment matrix
Preparation of ointments methods
- Incorporation
2. Fusion
Incorporation
Components mixed until uniform preparation is attained
Incorporation of solids
Ointment base placed on one side of working surface and powdered components, their particle size previously reduced*, on the other side, add powder with a portion of the base and continue with geometric dilution until all is combined and uniformly blended
Incorporation of liquids
Add only after due consideration of an ointment base’s
capacity to accept the volume required
*Levigating ointments
agent in which it is insoluble in
- reduces particle size of a powder before incorporation into the ointment base
When necessary to add an aqueous preparation to a hydrophobic base
the solution first may be incorporated into a minimum amount of hydrophilic
base, and then this added to the hydrophobic base
Fusion
All or some of the components of an ointment are combined by
being melted together and cooled with constant stirring until
congealed
- Components not melted are added as it is being cooled and stirred
Examples of ointments prepared by fusion
- beeswax
- paraffin
- stearyl alcohol
- high molecular weight PEGs
The method of manufacture for ointments having an emulsion base,
involves
both melting and emulsification
Microbial content
With the exception of ophthalmic preparations, topical applications are not required to be sterile; however, must meet microbial limits stated
by USP
– Antimicrobial preservatives used: Methylparaben, propylparaben and others
Minimum fill
Determination of net weigh or volume of contents of filled containers to
ensure proper contents compared with the labeled amount
Packaging, storage and labeling
Packaged in large-mouth ointment jars or in metal
or plastic tubes, must be stored in well-closed containers and in a cool place, light sensitive preparation are packaged in opaque or light-resistant containers, USP
directs labeling for certain ointments include the type of base used
Additional standards
Examine for viscosity and in vitro drug release to ensure within-lot and lot-to-lot uniformity
Cream
Semisolid preparation containing one or more medicinal agents
dissolved or dispersed in either a water-in-oil (W/O) or oil-in-water
(O/W) emulsion, or in another type of water-washable base
- Creams find primary application in topical skin products and
products used rectally and vaginally
creams vs. ointments patient wise?
Many patients and physicians prefer creams to ointments because
they are easier to spread and remove
How to prep of creams
May be formulated from a variety of oils and from fatty alcohols, fatty acids and fatty esters
- Solid excipients are melted at the time of preparation
Prep of creams steps:
Preparation usually involves separating the formula components into lipid and aqueous
➢ The lipid portion contains all water-insoluble components and the aqueous, the water-soluble
➢ Both phases are heated to a temperature above the melting point of the highest melting
component
➢ Phases are then mixed, and stirred until reaching ambient temperature
➢ Mixing generally is continued during the cooling process to promote uniformity
-Active ingredients can be added to the appropriate phase at the beginning of the process or after
cream is prepared by a suitable dispersion process, such as levigation
Creams: Emulsifying agents include
nonionic surfactants, detergents and soaps
Gels
Semisolid systems consisting of dispersions of small inorganic particles or large organic molecules in an aqueous liquid vehicle rendered jellylike by the addition of gelling agents
- May be formulated to contain a drug
- May be prepared for administration via skin, eye, nose, vagina and rectum
Gelling agents
Synthetic macromolecules (Ex. Carbomer 934)
- cellulose derivatives
(Ex. Carboxymethylcellulose) - natural gums (Ex. tragacanth)
Single-phase gel
Macromolecules uniformly distributed throughout liquid with no apparent boundaries between the dispersed macromolecules and the liquid
Two-phase system (or magma)
Gel mass consisting of floccules* of small distinct
particles
Example: Milk of magnesia
- *A loose aggregation of particles held together by weak bonds
Pastes
Semisolid preparations intended for skin
– Generally contain a larger proportion of solid material than ointments and are
stiffer
Pastes example
Zinc oxide paste to protect and soothe skin
Plasters
Solid or semisolid adhesive masses spread on a backing of paper, fabric, moleskin or
plastic
– Applied to skin to provide prolonged contact
– Example: Salicylic acid plaster for removal of corns
Plasters example
Salicylic acid plaster for removal of corns
Glycerogelatins
Plastic masses containing gelatin (15%), glycerin (40%), water (35%) and a medicinal
substance (10%)
– Applied to skin for long-term contact
Glycerogelatins example
Zinc gelatin for treatment of varicose ulcers
Topical dermatologic products are packaged
in jars, tubes or
syringes, whereas ophthalmic, nasal, vaginal and rectal semisolid
products are almost always packaged in tubes and syringes
Ointments and creams are susceptible to contamination by
Pseudomonas aeruginosa and Staphylococcus aureus, so preservatives added
Preservatives examples
- Parabens
- phenols
- benzoic acid
- quaternary ammonium
salts or sorbic acid
Dermatological preparations: In treating skin diseases, the drug should penetrate and be retained in the
skin for a period of time
•Substances with both aqueous and lipid solubility characteristics are good
candidates for passive diffusion through the stratum corneum (outer layer of the skin)
•Once through, drug molecules may pass through the deeper epidermal
tissues and into the dermis
• If drug reaches the vascularized dermal layer, it becomes available for
absorption into general circulation
Transdermal dermatological
preparations: Ointments, creams and gels designed to
deliver a drug through the
skin to the general circulation for systemic effects
-Accomplished by addition of penetration enhancers to the topical
vehicle
Transdermal dermatological
preparations: Some penetration enhancers:
Dimethyl sulfoxide
- ethanol
- PEG
- urea
- Spans
- Tweens
- lecithin
Oleaginous bases provide
greater occlusion (blockage) and emollient effects than do hydrophilic or water-washable bases
Pastes offer even
greater occlusion and are more effective than ointments
at absorbing serous discharge
Creams, usually oil-in-water emulsions,
spread more easily than ointments
and are easier to remove
Water-soluble bases are
non-greasy and are easily removed
For ophthalmic preparations: Semisolids used in the topical treatment of conditions and diseases of the eye
Ointments and gels
Major route by which drugs enter the eye is
simple diffusion via the cornea
Compared to ophthalmic solutions
ointments and gels provide extended
residence time on the surface of the eye, increasing the duration of their surface effects and bioavailability for absorption into the ocular tissues
Ophthalmic preparations
Ointment bases must not be irritating to the eye and must permit diffusion of medicinal substances throughout the secretions bathing the eye
- Ointment bases should have a softening point close to body temperature, for comfort and drug release
- Medicinal agents are added to an ointment base either as a solution or as a finely micronized powder, and the ointment made uniform and smooth by fine milling
Which are used as bases in ophthalmic ointments
mixtures of white petrolatum and mineral oil
A gel base of PEG and mineral oil is also used which
permit water and water insoluble drugs to be retained within the base
Ophthalmic ointments MUST meet the
USP sterility test and test for metal particles in ophthalmic ointments
USP directs that ophthalmic ointments must be packaged in
in collapsible ointment tubes, which have elongated narrow tips that facilitate application of a narrow band of ointment to the eye
Drugs introduced into the nasal passage are primarily
for local effects on
the mucous membranes and underlying tissues, i.e., nasal decongestants;
however, drug absorption to general circulation does occur through the
blood supply feeding the nasal lining
Nasal route is used
for the systemic absorption of a number of drugs
Nasal Preparations: semisolids used
Ointments and gels
The unit of viscosity is
the poise (p)
Lipophilic drugs are more capable
of penetration than hydrophilic compounds
Rectal preparations: Semisolids used
Ointments, gels, creams and cream-like aerosol foams
Rectal:Ointments, creams and gels are used
for topical application to the perianal area and insertion within the anal canal
What are rectal semisolids used for
Largely used to treat local conditions or anorectal pruritus inflammation and
the pain and discomfort associated with hemorrhoids
-used for systemic absorption of some drugs, when the oral
route is unsatisfactory
Rectal semisolids examples
Anusol and Tronolane
Rectal semisolids are
Substances may be absorbed by diffusion into the general circulation
Rectal semisolids bases
used include combination of PEG300 and 3350, emulsion cream bases using cetyl alcohol and cetyl esters wax, and white petrolatum and mineral oil
Vaginal preparations Semisolids used
Ointments, creams, creamlike foams and gels
Packaged in tubes and aerosol canisters
Vaginal Topical products used to treat
vulvovaginal infections, vaginitis, conditions of
endometrial atrophy and for contraception with spermatocidal agents
