CONTENT MODULE 3.

MODULE 2. SOFT AND ASEPTIC DOSAGE FORMS. PHARMACEUTICAL INCOMPATIBILITIES.

CONTENT MODULE 3.  SOFT MEDICAL FORMS. SUPPOSITORIES.

LESSON 15. OINTMENTS HOMOGENOUS.

 

DEFINITION:

“Ointments are semisolid preparation intended for application to the skin with or without inunction. they may be oleaginous e.g., white ointment; they may be entirely free of oleaginous substances e.g., polyethylene glycol ointment, or they may be emulsions of fatty or wax like material containing relatively high proportion of water e.g., hydrophilic ointment.”

IDEAL OINTMENT BASE:

According to BEELER, ideal ointment base should have following physicochemical properties:

1.     Stability

2.     Neutral in reaction

3.     Non greasy

4.     Non degreasing

5.     Non irritating

6.     Nondehydrating

7.     Non hygroscopic

8.     Water removable

9.     Compatible with all medicaments

10.    Free from odors

11.    Nonstaining

12.    Efficient on all skin type

13.    Composed of readily available component of known chemical composition

14.    Capable of holding 50% of water

15.    Easily compounded

Melting & softening at body temperature

 smoothness

 ease of application

Suitable  base

Properly distributed medicament

CLASSIFICATION OF OINTMENT/ OINTMENT BASES

ACCORDING TO PENETRATION:

1.EPIDEMIC OINTMENT :

Slight penetration power

Therapeutic effect on diseased epithelium

e.g,petrolatum,waxes and 1+2.

2.ENDODERMIC OINTMENT:

Power of deeper penetration

e.g,vegi oils,lards,lanolin and 1+2+3

3.DIADERMIC OINTMENT:

Penetrate skin effectively. better absorption

e.g., emulsion type & water soluble.

(PHYSICAL CLASSIFICATION ):

They may be classified into four main groups:

Hydrocarbon Bases

Absorption Bases

Water Miscible Bases

Water Soluble Bases

HYDROCARBON BASES:

Properties.

1.Anhydrous

2.Do not absorb water readily (Hydrophobic)

3. Insoluble in water

4.Not washable

Examples. Fats and fixed oils such as lard, olive oil, cottonseed oil, petrolatum(soft paraffin), white ointment, Yellow Ointment (Bees Wax) and silicon bases.

Advantages. Highly compatible; occlusive; good emollients.

Disadvantages. Difficult to remove from skin and clothing; uncertain as to yield of medicament.

May go rancid . allergies??

ABSORPTION BASES:

They may be:

Non emulsified: they absorb water and aqueous solutions to produce w/o emulsions. Examples are wool fat (anhydrous lanolin), wool alcohols, bees wax and cholesterol.

w/o emulsions: they are similar in properties to the previous group and are capable of absorbing more water. Examples are hydrous wool fat B.P. (lanolin) and oily cream B.P.

(a)Properties.

 Anhydrous

 will absorb water( hydrophillic)

Insoluble in water

most are not washable.

(b)Example. Hydrophillic Petrolatum, USP;  Anhydrous Lanolin, USP.

(c)  Advantages. Highly compatible; relatively stable to heat; can be used in anhydrous form or water can be added when emolliency is desired.

(d)Disadvantage. Greasy. Less occlusive.

EMULSION BASES:

Emulsion Ointment Base (W/O):

Hydrous

Will absorb water

Insoluble in water

Not washable

Water-Oil-Emulsion

Examples—Lanolin, Rose water Ointment, Cold Cream

Emulsion Ointment Base (O/W):

Hydrous

Will absorb water

Insoluble in water

Washable

Oil-in-Water Emulsion

Hydrophilic Ointment

Emulsion Bases. Emulsion ointment bases consist of an aqueous phase, an oleaginous phase, and an emulsifying agent. They are true, solid emulsions.

 Emulsion bases may be either oil-in-water (o/w) or water-in-oil (w/o), usually depending upon the phase in which the emulsifier is more soluble. The water phase varies from 10 percent to 80 percent of the completed ointment base.

They can be anionic, cationic, nonionic.

Combination:30:soft paraffin50: liquid paraffin20

(1)  Preparation. Emulsion bases are made by melting the greasy and oily materials together in one container and heating the water and water-soluble materials in another container.

At the temperature of 75° C, they are mixed together until a smooth cream results. While the mixture is still warm and thin, it may be passed through a homogenizer to improve the appearance and quality of the base.

The mixture is then stirred until it congeals.

Summary of emulsion bases. We can sum up the important aspects of emulsion bases as follows:

Properties. The w/o emulsion bases are insoluble in water and are not washable; the o/w emulsion bases are washable and nongreasy.

Example:

 Lanolin, USP (w/o);

 Hydrophilic Ointment, USP (o/w);

  Vanishing creams (o/w).

(c)Advantages:

 Washable and nongreasy if oil-in-water (o/w).

Disadvantages:

   Subject to water loss if o/w,

  greasy and unwashable if water-in-oil (w/o),

  unless, a preservative is added, the

emulsion   bases are subject to mold growth.

Water-Soluble Bases.

 The polyethylene glycol polymers, or Carbowaxes, are of great importance in ointments.

The names of the Carbowaxes include numbers that roughly indicate their average molecular weight.

Carbowaxes with a molecular weight in the area of 1,000 are soft, ointment-like substances.

 As the molecular weight increases, they become harder and they finally become waxes. They are water-soluble, nonvolatile, and do not deteriorate or support mold growth.

Properties:

 Anhydrous

 but will absorb water and dissolve in water;

Washable

Non-greasy.

(b) Examples. Carbowax compounds such as the polyethylene glycol bases containing pectin, cellulose, Bentonite, and gelatin.

c)  Advantages. Wide range of compatibility;

 do not become rancid or support microbial growth;

 nonirritating (to the same degree as lanolin, petrolatum, etc);

 adhere well to skin;

 easily washed off;

 low incidence of sensitization.

Disadvantages. Sometimes undergo gradual discoloration with certain drugs.

 Unless cetyl alcohol is added, an aqueous solution can be added only to the extent of 5 percent.

LANE & BLANK CLASSIFICATION:

According to physicochemical action of vehicle on skin:

VEHICLE ACTED AS AQEOUS MIXTURE

VEHICLE ACTED AS OILS

VEHICLE ACTED AS POWDERS

VEHICLE ACTED AS ORGANIC SOLVENT

CLASSIFICATION OF OINTMENT/ OINTMENT BASES

CHEMICAL CLASSIFICATION:

Hydrocarbon

Alcohol

Acid

Ester

SOAPS

MISCELLANEOUS

ACCORDING TO USES OR THERAPEUTIC CLASSIFICATION:

1.                     Emollient

2.                     Protective

3.                     Anti Infectives

4.                     Anti Eczematic

5.                     Keratolytic

6.                     Anti Prespirants

7.                     Anti Sebhorrics

METHOD OF PREPARATION

MIXING BY FUSION:

In this method, the ingredients are melted together and stirred to ensure homogeneity.

On a small scale, fusion is usually fusion is usually carried out in an evaporating basin made of glazed porcelain or stainless steel over a water bath.

PREPARATION OF OINTMENT BASE BY FUSION:

The constituents of the base are melted together in the basin and stirred gently after melting until cool.

Vigorous stirring can cause aeration which should be avoided.

Any foreign particles that are naked on melting cam be removed by decantation or by using a warm muslin cloth.

If product is granular after cooling due to separation of some ingredients of high MP, it may be remelted with min. heat and restirred until cold.

Stock bases can be made successfully by pouring the melted mixture into a warmed jar, covering and allowing to stand, undisturbed on a non conducting surface, until set. (paraffin, simple or wool alcohol ointments of B.P.)

Completely or partially soluble solids should be added in fine powder to the molten base at very low temperature and the mixture stirred until cold.

Liquids such as methyl salicylate and coal tar solutions and semi solids such as ichthammol should be added just as the base is thickening, at about 40C. When a solid is soluble in liquid ingredient, (menthol in methyl salicylate), its more convenient to add it in solution.

Insoluble solids (calamine, starch, zinc oxide) should be passed through a 180 um sieve and added in small amount while stirring to melted base, when it shows first sign of thickening. Sedimentation should be prevented.

If the product has liquid paraffin or a fixed oil, small amount can be used to levigate powder before adding to base to produce a smoother product.

MIXING BY TRITURATION:

This is applicable when medicament is a solid insoluble in base or a liquid present in small amount.

Solids should be finely powdered and passed via sieve. (250 um/180 um/125 um mesh).

Trituration can be carried out with an ointment tile and a spatula or using mortar and pestle.

TRITURATION USING TILE AND SPATULA:
Tiles should be large enough to prepare ointments.

Spatula should be flexible and have a broad, non-tapering long blade, to provide a large rubbing surface.

Another small spatula may be used for removing accumulated material.

Powders for incorporation are placed on the tile and mixed gently.

Powders are levigated until mixture is smooth and homogenous.

Dispersion is then diluted with increasing amounts of base, doubling the quantity on each addition.

Finally any liquid ingredients are incorporated, avoiding splashes.

TRITURATION USING MORTAR AND PESTLE:

The mortar should have a flat base and the pestle is flat headed to give best results.

Warming equipment can be helpful if the base is very stiff.

Sequence of mixing is same as for the tile method.

Splashing of liquids is easily controlled in the mortar.

METHOD OF PREPARATION

Incorporation of solids

Incorporation of gummy materials.

Incorporation of liquids.

PACKAGING,STORAGE& LABELLING:

 

Learning Objectives

Upon completion of this exercise, you should be able to:

·  Classify an ointment base formulation as 1 of 5 types.

·  Describe the physical properties of ointment bases and determine the purposes for which they are best suited.

·  Extemporaneously prepare each type of ointment base and incorporate a solid drug into it.

·  Relate the composition and type of ointment base to the release of a drug contained therein.

·  Introduction

· 

·  Ointments are used topically for several purposes, e.g., as protectants, antiseptics, emollients, antipruritics, kerotolytics, and astringents. The vehicle or base of an ointment is of prime importance if the finished product is expected to function as any one of the above categories. In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors. It is necessary that the ointment neither penetrates the human skin barriers nor facilitates the absorption of substances through this barrier. An antiseptic ointment is used to destroy or inhibit the growth of bacteria. Frequently bacterial infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is therefore desired. Ointments used for their emollient effect should be easy to apply, be non-greasy and effectively penetrate the skin.

Dermatological Formulations: Ointments and Pastes

Dermatological formulations are among the most frequently compounded products because of their wide range of potential uses. These include solutions (i.e., collodions, liniments, aqueous and oleaginous solutions), suspensions and gels, emulsions, lotions, and creams. Lotions can be either suspensions or emulsions but are fluid liquids that are typically used for their lubricating effect. Creams are emulsions and are typically opaque, thick liquids or soft solids used for their emollient properties. Creams also have the added feature that they tend to “vanish” or disappear with rubbing. Distinctions between lotions and creams are open to individual interpretation.

Other dermatological formulations that are not commonly compounded include aerosols, dusting powders, and devices such as transdermal patches, tapes, and gauzes. These formulations are typically manufactured.

This chapter will deal with two other dermatological formulations, ointments and pastes. Pastes have more solid material in them than ointments. These two formulations are also termed “semisolids” because they appear to be solid but still have fluid properties.

Local and Systemic Effects of Dermatological Formulations

Regardless of the formulation, all dermatological formulations are applied to the skin.

The skin is the largest and heaviest organ in the body and accounts for about 17% of a person’s weight. Its major function is to protect the underlying organ systems from trauma, temperature, humidity, harmful penetrations, moisture, radiation, and microorganisms. It is composed of three layers of stratified tissue: epidermis, dermis, and subcutaneous tissue. The thickness of the skin is 3 – 5 millimeters. The thickness of the skin varies with the different parts of the body. The thickest parts of the skin are the palms and soles and the thinnest parts are the eyelids and genitals. Within the structure of the skin are several skin appendages: hair follicles, sebaceous glands, sweat glands, and nails.

In normal skin, the epidermal cells are continually replenished by the formation of initially viable cells from the basal germinative layer. As the new cells develop, they displace the outer epidermal cells. The outer layer is called the stratum corneum and these cells are sloughed off to the environment. As the cells migrate to become the stratum corneum, they become flattened, lose their nuclei, and the organized cell contents becomes replaced with keratin fibrils. The turnover time from germination to sloughing is about 21 days.

It is the stratum corneum that is the barrier to drug penetration through the skin. The stratum corneum is approximately 10 microns thick. It can swell to approximately three times its original thickness and absorb about five times its weight in water. When the stratum corneum hydrates, it becomes more permeable. Therefore, occlusive dressings are often used to hydrate the stratum corneum and increase the penetration of certain drugs. Dermatoses such as eczema and psoriasis can also hydrate the stratum corneum and increase the absorption of some drugs.

Dermatological formulations produce a local drug effect either on or in the skin. Besides the specific therapeutic action of incorporated active drugs, the formulations also as serve as protectants, lubricants, emollients, or drying agents. Examples of treatments using dermatological formulations include minor skin infections, itching, burns, diaper rash, insect stings and bites, athlete’s foot, corns, calluses, warts, dandruff, acne, psoriasis, and eczema.

Some dermatological formulations are intended to systemically deliver a drug. Percutaneous (through the skin) absorption is the result of three competing processes:

1.                     the potential of the drug to cross the stratum corneum

2.                     the potential of the drug to leave the formulation

3.                     the influence of the formulation on the stratum corneum.

Although the percutaneous absorption of drugs is a complex process, several generalizations are possible:

1.                     More drug is absorbed when the formulation is applied to a larger surface area.

2.                     Formulations or dressings that increase the hydration of the skin generally enhance percutaneous absorption.

3.                     The greater the amount of rubbing in or inunction of the formulation, the greater the absorption.

4.                     The longer the formulation remains in contract with the skin, the greater will be the absorption.

Percutaneous administration affords an ease of administratioot found in other routes, and patient compliance is generally good with dermatological formulations. There is also the possibility of continuous drug administration exemplified by the transdermal patches. In addition, dermatological formulations can be easily removed if necessary.

The major disadvantage of this route of administration is that the amount of drug that can be absorbed will be limited to about 2 mg/day. This may become a significant limitation if the route is being considered for systemic therapy. However, several chemicals have been found that promote the percutaneous absorption of drugs. These “penetration enhancers” improve the solubility of the active drug in the stratum corneum and facilite the diffusion of the drug through this barrier into the systemic circulation. Below is a list of penetration enhancers used in dermatological formulations. (reference 1) Other commonly used enhancers include DMSO (dimethyl sulfoxide), urea, and triethanolamide.

Ointment Bases

There are five (5) classes or types of ointment bases which are differentiated on the basis of their physical composition. These are:

·  oleaginous bases

·  absorption bases

·  water in oil emulsion bases

·  oil in water emulsion bases

·  water soluble or water miscible bases

Each ointment base type has different physical characteristics and therapeutic uses based upon the nature of its components. The following table summarizes the composition, properties, and common uses of each of the five types. For more information consult Remington’s.

SUMMARY CHART: PROPERTIES OF OINTMENT BASES

	Oleaginous Ointment Bases	Absorption Ointment Bases	Water/Oil Emulsion Ointment Bases	Oil/Water Emulsion Ointment Bases	Water-miscible Ointment Bases
Composition	oleaginous compounds	oleaginous base + w/o surfactant	oleaginous base + water (< 45% w/w) + w/o surfactant (HLB <8)	oleaginous base + water (> 45% w/w) + o/w surfactant (HLB >9)	Polyethylene Glycols (PEGs)
Water Content	anhydrous	anhydrous	hydrous	hydrous	anhydrous, hydrous
Affinity for Water	hydrophobic	hydrophilic	hydrophilic	hydrophilic	hydrophilic
Spreadability	difficult	difficult	moderate to easy	easy	moderate to easy
Washability	nonwashable	nonwashable	non- or poorly washable	washable	washable
Stability	oils poor; hydrocarbons better	oils poor; hydrocarbons better	unstable, especially alkali soaps and natural colloids	unstable, especially alkali soaps and natural colloids; nonionics better	stable
Drug Incorporation Potential	solids or oils (oil solubles only)	solids, oils, and aqueous solutions (small amounts)	solids, oils, and aqueous solutions (small amounts)	solid and aqueous solutions (small amounts)	solid and aqueous solutions
Drug Release Potential*	poor	poor, but > oleaginous	fair to good	fair to good	good
Occlusiveness	yes	yes	sometimes	no	no
Uses	protectants, emollients (+/-), vehicles for hydrolyzable drugs	protectants, emollients (+/-), vehicles for aqueous solutions, solids, and non-hydrolyzable drugs	emollients, cleansing creams, vehicles for solid, liquid, or non-hydrolyzable drugs	emollients, vehicles for solid, liquid, or non-hydrolyzable drugs	drug vehicles
Examples	White Petrolatum, White Ointment	Hydrophilic Petrolatum, Anhydrous Lanolin, Aquabase™, Aquaphor®, Polysorb®	Cold Cream type, Hydrous Lanolin, Rose Water Ointment, Hydrocream™, Eucerin®, Nivea®	Hydrophilic Ointment, Dermabase™, Velvachol®, Unibase®	PEG Ointment, Polybase™

*Varies depending upon specific content of the ointment base and the relative polarity of the drug(s) incorporated. This table refers more generally to the release of a typical nonelectrolyte (primarily lipophilic) drug.

Preparation of Ointment Bases

Prepare 120 g of each of the following five ointments on a w/w basis. One partner should prepare bases #1, 3 and 5 while the other prepares #2 and 4. Make sure that you follow closely the procedures for preparation.

General Comments About Compounding Ointment Bases

·  Between 2 and 4 grams of an ointment may be lost in the compounding process. The ointment is lost as it adheres to beakers, ointment tiles, or ointment pads. To compensate for this loss, make an excess of the ointment. Some general rules might be to add 10% or 3 grams excess to the prescribed amount.

·  When heat is used to melt ingredients, use a water bath or special low temperature hotplate. Most ingredients used in ointment bases will liquefy around 70°C These two heating devices provide adequate control over the heating and will ensure that the ingredients are not over heated. A water bath will only heat to the boiling point of water which is 100°C. Special “low temperature” hotplates (full range is 25°C to 120°C) are not a standard laboratory type hotplate; those hotplates heat at 125°C to 150°C at their lowest setting.

·  When both an oil and aqueous phase are being mixed together to make an ointment, it is helpful to heat the aqueous phase a few degrees higher than the oil phase prior to mixing. The aqueous phase tends to cool faster than the oil phase and may cause premature solidification of some ingredients. However, use the lowest temperature possible and keep the time of heating as short as possible. This will minimize the quantity of water lost through evaporation.

·  When melting a number of ingredients, melt the ingredient with the highest melting point first. Then gradually reduce the heat to melt the ingredient with the next lowest melting point. Continue this process until all ingredients have been added. This will ensure that the ingredients were exposed to the lowest possible temperature and thus enhance the stability of the final product.

·  The cooling step in an ointment’s preparation is an important part of the compounding process.

o          Do not accelerate the cooling process by putting the melt in water or ice. This will change the consistency of the final product making it more stiff than desired.

o          If adding volatile ingredients such as oils, flavors, or drugs, add them when the product is “cool to the back of the hand.” The melt will still be fluid enough for adequate mixing but not hot enough to evaporate the ingredient.

o          Ointments should be cooled until just a few degrees above solidification before they are poured into tubes or jars. They should be thick, viscous fluids. This will minimize “layering” of the ointment in the packaging container. However, this is not the preferred method of packing an ointment tube or jar.

o          Most bases achieve their final consistency and texture several hours after they are compounded.

BASE NO. I: Oleaginous Base (White Ointment)

White Wax	5%	________ g
White Petrolatum	95%	________ g

Procedure for Preparation:

a.                     Melt the white wax on a hot plate. No need to heat beyond 70 – 75°C

b.                     When the wax has completely melted, add the petrolatum and allow the entire mixture to remain on the hot plate until liquefied.

c.                      Following liquefication, remove from heat and allow the mixture to congeal. Stir the mixture until it begins to congeal.

BASE NO. II: Absorption Base

Cholesterol	3%	________ g
Stearyl Alcohol	3%	________ g
White Wax	8%	________ g
White Petrolatum	86%	________ g

Procedure for Preparation:

a.                     Melt the stearyl alcohol, white wax, and petrolatum together on a hot plate.

b.                     Add the cholesterol to the mixture; stir until completely dissolved.

c.                      Remove the mixture from the hot plate and stir until congealed.

BASE NO. III: W/O Emulsion Base (Cold Cream type base)

White wax	12.0%	________ g
Cetyl Esters Wax (or Spermaceti)	12.5%	________ g
Mineral Oil (Sp Gr = 0.9)	56.0%	________ g	________ ml
Sodium Borate	0.5%	________ g
Water	19.0%	________ g	________ ml

Procedure for Preparation:

a.                     Melt the white wax and spermaceti on a hot plate.

b.                     Add the mineral oil to this mixture and bring the temperature to 70°C.

c.                      Dissolve the sodium borate in water.

d.                     Heat the sodium borate solution to 70°C.

e.                      When both phases have reached the desired temperature, remove both phases from the hot plate and add the aqueous phase slowly and with constant stirring to the oil phase.

f.                       Stir briskly and continuously until congealed.

BASE NO. IV: O/W Emulsion Base (Hydrophilic Ointment)

Sodium Lauryl Sulfate	1.0%	________ g
Propylene Glycol (SP Gr = 1.035)	12.0%	________ g	________ ml
Stearyl Alcohol	25.0%	________ g
White Petrolatum	25.0%	________ g
Purified Water	37.0%	________ g	________ ml

Procedure for Preparation:

a.                     Melt the stearyl alcohol and white petrolatum on a hot plate.

b.                     Heat this mixture to 70°C.

c.                      Dissolve remaining ingredients in water and heat the solution to 70° C.

d.                     Add the oleaginous phase slowly to the aqueous phase, stirring constantly.

e.                      Remove from heat and stir the mixture until it congeals.

BASE NO. V: Water Soluble Base

Polyethylene Glycol 400 (SP Gr = 1.12)	60%	________ g	________ ml
Polyethylene Glycol 3350	40%	________ g

Procedure for Preparation:

a.                     Melt the PEG 400 and Carbowax 3350 on a hot plate.

b.                     Warm the mixture to about 65°C.

c.                      Remove from the hot plate and stir until congealed.

 

 

INTRODUCTION

TOPICAL APPLICATION

  * to the skin

  * place on the surface of the eye

  * vaginally, nasally, rectally

TOPICAL DERMATOLOGICAL designed to deliver drug    into the skin – dermal disorders (SKIN AS TARGET        ORGAN)

TRANSDERMAL designed to deliver drug through skin       (percutaneous absorption) – general circulation –      SKIN NOT BEING THE TARGET ORGAN

NOTE:  SYSTEMIC ABSORPTION – always considered

 

Unguents are semisolid preparations         for external application of such          consistency that they maybe readily         applied to the skin with or without inunction (rubbing)

Ointments should be of such   composition that they soften but     not necessarily melt when applied       to the body.

General Uses Of Ointments

1.  Acts as protective or protectant –                   serve as physical barrier to                       environment

2.  Acts as emollient – softens skin                       and makes it pliable

3.  Carrier of medicament – vehicle

Types Of Ointments

1.                      Medicated – those with medicaments for treatments of cutaneous (skin diseases).

  Examples: Sulfur Ointment, Zinc Oxide   Ointment and Compound Resorcinol

1.                      Non-medicated – also referred to as “ointment bases” and use as such for their emollient or lubricating effect or use as vehicles in medicated ointments. 

  Example:  White Ointment

The USP and NF Classify Ointment Bases into Four General Groups

1.  Hydrocarbon bases or                              Oleaginous bases

2.  Absorption bases

3.  Water removable bases or              Emulsion Ointment bases

4.  Water soluble bases

Factors Of Selecting Ointment Bases

1.  Physicochemical properties of the medicaments as stability in the base or influence on consistency.

2.  Patient’s conditions – as to the desired release rate of the drug from the base.

3.  Intended site of application – ability of occlusion of moisture from the         skin by the base.

4.  Characteristics of the various vehicles available – use the one which provided the majority of essential attributes

HYDROCARBON BASES

n     Are water-free, and aqueous preparations may only be incorporated into them in small          amounts and then with difficulty.

USES: HC are use mainly for their emollient       effect and not intended for penetration into   the skin.  They are difficult to wash off.     They do not “dry out” or change noticeably          upon aging.

Characteristics

1.  Retained on the skin for prolong             period of time

2.  Do not permit the escape of                   moisture to the skin to the                        atmosphere

3.  Difficult to wash as such they acts                   as occlusive dressing

4.  They do not change noticeably                upon aging

n     Sources Of Hydrocarbon Bases

1.  Vegetable Oil – Mineral oil

2.  Animal Fat – Oleic oil

1.                        HC from Petrolatum 

3 Forms of HC

  a.  Liquid hydrocarbon – Mineral oil        

  b.  Semi-solid HC petrolatum – Vaseline

  c.  Solid HC – Paraffin

HYDROCARBONS BASES

l     Characteristics

Insoluble in water

Not water-washable

Anhydrous

Will not absorb water

Emollient

Occlusive

Greasy

Nonirritating

Inexpensive, non reactive

l     Examples

White Petrolatum

White Ointment

Vegetable shortening

Vaseline

Examples Of Hydrocarbon Bases

n     Petrolatum, NF – mixture of semisolid HC obtained from petroleum

Properties:  An unctous mass, color yellowish to light amber,                            melts between 38⁰C -60⁰C

Synonyms:  Yellow petrolatum, Petroleum jelly

    Commercial Product: Vaseline

n     White Petrolatum, USP – is petrolatum that has been decolorized

    Used: diaper rash, dry skin

    Synonym: White Petroleum Jelly

    Commercial Product:  White Vaseline

n      Yellow Ointment – Each 100 g contains 5 g yellow wax and 95 g of        petroleum. Yellow wax is purified wax obtained from         honeycomb of the bee (Apis mellifera)

     Synonym:  Simple Ointment

n     White Ointment, USP – 100 g contains 5% of white    wax (bleached purified beeswax) and 95%        white petrolatum

n     Paraffin, NF – is a purified mixture of solid HC           obtained from petroleum

      Characteristics: colorless or white, more or    less translucent mass that may be used to      harden or stiffen oleaginous semisolid ointment          bases.

n     Mineral Oil, USP – is a mixture of liquid HC obtained          from petroleum. Useful  in levigating of     substances insoluble in it in the preparation of ointment base e.g. Salicylic acid, Zinc oxide

      Synonym:  Liquid Petrolatum

n     Olive Oil, USP – from crushed olives- also called        sweet oil

OFFICIAL ABSORPTION BASES

2 TYPES

n     Those that permit the incorporation of aqueous solutions resulting in the formation of water-in-oil emulsion. (Anhydrous absorption bases)

   Examples: Hydrophilic Petrolatum and                                  Anhydrous Lanolin

n     Those that are already water-in-oil emulsion (emulsion base) that permits the incorporation of small additional quantities of aqueous solution

  Examples: Lanolin and Cold cream; water                                     soluble drugs: Gentamycin                                       Sulfate

n     Characteristics

1.                     Not easily removed from skin with water washing,

2.                     May possess some power of penetration into the        deepest layers of the skin

3.                     And therefore are used for “endodermic”          ointment.

n     USES

1.                     As emollient but do not provide the degree of    occlusion

2.                     Incorporates aqueous solutions into oleaginous          bases

EXAMPLES OF ABSORPTION BASES

1.  Hydrophilic Petrolatum, USP – composed of   cholesterol, stearyl        alcohol, white wax and     white petrolatum

  Characteristics: It has the ability to absorb        water with the formation of W/O emulsion

  Example: Aquaphor

2.  Anhydrous Lanolin, USP – may contain NMT          0.25% water.

  Characteristics: It is insoluble in water but         mixes without separation with about 2x its      weight in water.  The incorporation of water     results in the formation of a W/O emulsion

  Synonym:  Refined Wool Fat

3.  Lanolin, USP – is a semisolid fat like substance        obtained from the wool of sheep (Ovis aries)

  Characteristics: It is a W/O emulsion that          contains between 25 to 30% water.  Additional water may be incorporated into lanolin by mixing

  Synonym: Hydrous Wool Fat

4.  Cold Cream, USP – is a semi solid white  W/O         emulsion prepared with cetyl esters wax, white          wax, mineral oil, sodium borate, and purified    water

  Examples: Eucerin cream – is a W/O emulsion   of petrolatum, mineral oil, mineral wax, wool wax, alcohol and bronopol. Cold cream –           emollient and base.

1.  Anhydrous Absorption Bases

l     Characteristics

Insoluble in water

Not water washable

Anhydrous

Can absorb water

Emollient

Occlusive

Greasy

l     Examples

Hydrophilic Petrolatum

Lanolin

Aquaphor

Aquabase

Polysorb

2.  Water-in-oil Emulsion

l     Characteristics

Insoluble in water

Not water washable

Contains water (limited)

Emollient

Occlusive

Greasy

l     Examples

Hydrous Lanolin

Cold Cream

Eucerin

Hydrocream

Rose Water Ointment

WATER REMOVABLE BASE

n     Are oil-in-water emulsion that are   capable of being washed from         skin or clothing with water.      For this reason, they are         frequently referred to as         “water-washable” ointment      base.

WATER REMOVABLE BASES

n     Characteristics

1.  Resemble creams in their                        appearance

2.  May be diluted with water or with                   aqueous solution

3.  From therapeutic viewpoint, no              ability to absorb serous discharge in         dermatologic conditions

4.  Certain medicinal agents may be           better absorbed in the skin

Water Removable (O/W Emulsion)

l     Characteristics

Insoluble in water

Water washable

Contains water

Can absorb water

Non-occlusive

Non-greasy

l     Examples

Hydrophilic Ointment

Vanishing Cream

Dermabase

Velvachol

Unibase

WATER SOLUBLE BASE

n     Unlike water-removable bases, which       contains both water soluble and           water insoluble components.  Like water-removable bases, however,    water soluble bases are water    washable and are commonly referred to as “greaseless”     because of the absence of any     oleaginous materials

n     Characteristics

1.  Because they soften greatly with the      addition of water, aqueous solutions are   not effectively incorporated into these   bases. Rather, they are better used for      the incorporation of non-aqueous or solid          substance.

2. These penetrated the skin and better       used for absorption of medicament and          therefore used for “diadermic           ointment”. 

  Example:    Polyethylene Glycol       Ointment, USP is a combination of 400    g of polyethylene glycol 4000 (solid) and        600 g of polyethylene glycol 400 (liquid) to prepare 1000 g of base.

WATER SOLUBLE BASES

l     Characteristics

Water soluble

Water washable

May contain water

Can absorb water (limited)

Non-occlusive

Non-greasy

Lipid-free

l     Example

Polyethylene Glycol Ointment

SELECTION OF THE APPROPRIATE BASE

1.  The desired release rate of the particular         drug substance from the ointment base.

2.  The desirability for enhancement by the base of the percutaneous absorption of the drug.

3.  The advisability of occlusion of moisture from        the skin by the base.

4.  The short term and long term stability of the drug in the ointment base

5.  The influence, if any, of the drug on the          consistency or other features of the          ointment base.

PREPARATION OF OINTMENT

1.  INCORPORATION

n              The components of the ointment are mixed        together by various means until a uniform     preparation has been attained.

n              In small scale or in extemporaneous         compounding of the Rx, the pharmacist may   use 2 means:

a.  Mixing ingredients in a mortar with pestle      until smooth ointment produced

b.  Use a spatula and an ointment slab (a large    glass or porcelain plate) to rub the ingredients together (spatulation)

n     Incorporation Of Solid

  In preparing ointment by spatulation, the pharmacist works the ointment with a stainless steel spatula but if the components react with metal (such as iodine, tannins, mercuric salts) the hard rubber is used

1.  The ointment base is placed on one side of the         working surface.

2.  The powdered components (previously reduced      into fine powders) are placed on the other side.

3.  Then a portion of the powder is mixed with a          portion of the base until uniform.

4. Repeat until all portions of the product and based    are combine.

5. The portions of prepared ointment are then     combined and thorough blended by continuous movement of the spatula.

n     Incorporation Of Liquids

  Liquid substances or solutions of drugs are added to an ointment only after due consideration of the ointment nature.

  An aqueous solution would be added with difficulty to the oleaginous ointment, except in very small amount.  However, water absorbable hydrophilic ointment bases would be quite suitable for the absorption and incorporation of the aqueous solution.

  In case of of hydrophobic base and an aqueous solution is to be added, a portion of the hydrophobic base is replaced by a hydrophilic base.

2.  FUSION METHOD

  By this method, all or some of the components of an ointment are combined by melting together and cooled with constant stirring until congeal.

  Those components not melted are generally added to the congealing mixture as it is cooled and stirred.

  The heat labile substances and volatile constituents are added last when temperature is low enough not to cause decomposition.

n     Packaging and Storage Of      Ointments

 

Semisolid pharmaceuticals frequently either in jars or in tubes.  The jars may be made of glass, uncolored, colored green, amber or blue or opaque and porcelain white.  Plastic jars are used in limited extent.  The tubes are made of tin or plastic.  These are called “collapsible tube”.

TESTS REQUIREMENTS FOR OINTMENTS

1.                     Microbial Content

  Meet acceptable standard for microbial

  Must contain antimicrobial preservatives

Preservatives:

  methylparaben,propyl paraben, phenols, benzoic acid, sorbic,quaternary ammonium salts

Example:  Betamethasone Valerate Ointment – must be absence of Staphylococcus aureus and Pseudomonas aeriginosa

TESTS Requirements for Ointments

•  Minimum Fill Test – net weight and volume

•  Packaging, Storage, and Labeling – metal, plastic tubes, jar

  Well close containers, light sensitive, light resistant

  Labeling- type of base used (water soluble or insoluble)

4.                     Additional Standards

  Examine the viscosity

  Vitro drug release to ensure within lot and lot-to-lot uniformity

n     Tubes May Be Filled By The Following Steps

1.  The prepared ointment is rolled into a cylinder shape       of a piece of parchment paper, the diameter is   smaller than that of the tube.

2.  With cap of the tube off to permit escape of air, the          cylinder of ointment with the paper is inserted into    the open bottom of the tube

3. The piece of paper covering the ointments is grasped         in one hand, the other hand forces a heavy spatula down on the extreme end of the tube, collapsing it      and retaining the ointment while the paper is slowly pulled from the tube.  About one half (1/2) inch of      the bottom is then flattened with the spatula.

4.  About 1/8 folds are made from the flattened end of the tube and sealed by pliers or sealing clip on foot        operated “crimper” machine.

n     Note: Ointments made by fusion may be poured directly     into the tubes. Stored at temperatures below 30^oC to        prevent softening.

 

 

 

 

 

•  Ointments are semisolid preparations intended for topical application.

•  Most ointments are applied to the skin, although-they may also be administered ophthalmically, nasally, aurally, rectally, or vaginally.

•  With few exceptions, ointments are applied for their local effects on the tissue membrane rather than for systemic effects.

•  It is possible for systemic effects to occur after the topical application of medications.

•  Systemic absorption, which takes place through the skin’s surface, is referred to as ……………………….

•  Percutaneous absorption may be enhanced by many factors:

1.                     ………………………;

2.                     Through the hydrophilic­lipophilic nature of the drug;

3.                     By virtue of the occlusive features of the topical preparation and/or dressing.

 

•  Non-medicated ointments serve as the vehicles, or ointment bases, for the addition of medication.

•  Ointment bases are usually of four general types:

 (1) hydrocarbon or oleaginous bases (………………………), which do not mix well with aqueous preparations and provide an ……………………… barrier to the skin;

(2) absorption bases (such as lanolin), which permit the absorption of aqueous solutions, usually resulting in W/O emulsions;

(3) water­removable bases (hydrophilic ointment), which are oil-in-water emulsions, or,

(4) water-soluble bases (polyethylene glycol ointment), both of which are water washable.

 

•  In preparing a medicated ointment, the appropriate ointment base is selected to which the medication is added.

•  The solid and semisolid materials in ointments are generally weighed in preparing a prescription or product.

•  Liquid components may be measured ………………………or converted by calculation to corresponding weight and then weighed.

•  Because ointments are semisolid preparations, they are also ………………………, ………………………, and ………………………on a weight basis.

•  Special care must be taken in the preparation of ophthalmic ointments to render them:

1.                     free from ……………………… and

2.                     to assure that the powders used in the formulation are either dissolved or micronized to reduce or eliminate ……………………… that could cause eye irritation.

 

Ointments are any greasy or oily semi-solid preparation, usually medicated, that can be applied externally to the skin in order to heal, soothe or protect it.

It is a viscous semisolid preparation used topically on a variety of body surfaces.

Drug ingredients can be dissolved, emulsified or suspended in the ointment base.

The word ointment comes from the Latin ungere meaning anoint with oil.

Are ointments of a particularly soft consistency they are usually emulsion ointments.

They are viscous liquid or semisolid emulsions of oil-in-water or water-in-oil type.

Easier to spread and easier to remove than ointments.

Have very solid consistency and contain usually relatively large quantities of solids.

Contain a larger percentage of solid material than ointments (thicker and stiffer).

Will not soften and flow after application .

Ointments are used topically for several purposes, e.g., as protectants, antiseptics,      emollients, antipruritics, kerotolytics, and astringents.

 In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors.

It is necessary that the ointment neither penetrates the human skin barriers nor facilitates the absorption of substances through this barrier.

An antiseptic ointment is used to destroy or inhibit the     growth of bacteria.     Frequently bacterial    infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is therefore desired.

 Ointments used for their emollient effect should be easy to apply, be non-greasy and effectively penetrate the skin.

There are five (5) classes or types of ointment bases which are differentiated on the basis of their physical composition. These are:

Oleaginous bases.

Absorption bases.

Water in oil emulsion bases.

Oil in water emulsion bases.

Water soluble or water miscible bases.

These bases are fats, fixed oils, hydrocarbon or silicones.

They are anhydrous, greasy, non-washable does not absorb water and occlusive (form a film on skin so it increases the skin hydration by reducing the rate of loss of surface water.

They should not be applied to inffected skin.

 they are used as protectants, emollients , vehicles for hydrolyzable drugs.

Example: White Petrolatum, White Ointment

Oleaginous base + w/o surfactant.

Anhydrous but hydrophilic ointment bases, they can absorb several times their weight of water to form water-in-oil emulsion.

They are non-washable, not water soluble

They used as protectants, emollients (+/-), vehicles for aqueous solutions, solids, and non-hydrolyzable drugs.

Example: Hydrophilic Petrolatum, Anhydrous Lanolin, Aquabase™, Aquaphor®, Polysorb®

These are anhydrous, hydrophilic, absorbs water and non water removable, with low thermal conductivity and occlusive.

They have the same properties   as the absorption basees.

They are used as emollients, cleansing creams, vehicles for solid, liquid, or non-hydrolyzable drugs .

Examples: Cold Cream type, Hydrous Lanolin, Rose Water Ointment, Hydrocream™,  Eucerin®, Nivea® .

These bases are anhydrous, water soluble, absorb water and water washable.

They are either carbowaxes Polyethylene Glycols (PEGs) or hydrated gums (bentonite, gelatin, cellulose derivatives).

They are used as drug vehicles.

Examples: PEG Ointment, Polybase™

These bases are anhydrous, water soluble, absorb water and water washable.

They are either carbowaxes Polyethylene Glycols (PEGs) or hydrated gums (bentonite, gelatin, cellulose derivatives).

They are used as drug vehicles.

Examples: PEG Ointment, Polybase™

Selection of the Appropriate Base Based on:

1.     Desired release rate.

2.     Desirability for enhancement    of percutaneous absorption.

3.     Advisability of occlusion.

4.     Short-term or long-term stability.

5.     Influence of drug on consistency or other features of ointment base.

6.     Patient factor – dry or weeping (oozing) skin.

Among the properties which an Ideal ointment base should possess are:

1.     Does not retard wound healing.

2.     Low sensitization index.

3.     Pharmaceutical elegance.

4.     A low index of irritation.

5.     Non dehydrating.

6.     Non greasy.

7.     Neutral in reaction.

8.     Good keeping qualities.

9.     Compatible with common medicaments.

10.    Efficient release of medicament at site of application.

11.    Washability (easily removed with water).

12.    Minimum number of ingredients.

13.    Ease of compounding.

Preparation of ointment

Mix together (mortar & pestle, spatula & slab)

roller mill

“levigating” the powder (reduction of particle size in suspending agent compatible with the ointment base)

In porcelain dish all or some components of an ointment melted together and     cooled with constant stirring until congealed, add non-melting substances as the ointment is being cooled and stirred.

Store and dispensing

Ointments should be stored in tightly closed and completely filled containers

Changes in temperature can lead to the crystallization of the drug and to changes in the ointment base.

They are usually dispensed in jars of glass or plastic material or in collapsible tubes.

Sterile ointments must be dispensed in tubes or single dose units in order to protect the product against contamination during use.

With tin tubes, there is a risk of corrosion with hydrophilic ointments.

Packaging and storage

•         Prepare the ointment. Select an ointment jar that will just hold     all of the formulation.

•         Begin by taking some ointment.

•         ….. and fill the bottom of             the ointment jar. Use the     spatula to put ointment               into the crevices.

•         Continue adding ointment to the jar again using the spatula to put the ointment along the sides of the jar.

•         As you fill the jar, stab the spatula into the ointment a couple of times. This will reveal air    pockets that may have formed.

•         Put the spatula halfway           across the filled jar, and               tilt in slightly.Rotate the            jar…

•         …and this is make a professional looking finish on the top of the ointment.

•         Wipe off ointment from the threads of the jar.

•         Cap the ointment jar.

 

Learning Objectives

Upon completion of this exercise, you should be able to:

Classify an ointment base formulation as 1 of 5 types.

Describe the physical properties of ointment bases and determine the purposes for which they are best suited.

Extemporaneously prepare each type of ointment base and incorporate a solid drug into it.

Relate the composition and type of ointment base to the release of a drug contained therein.

Introduction

 

 Ointments are used topically for several purposes, e.g., as protectants, antiseptics, emollients, antipruritics, kerotolytics, and astringents. The vehicle or base of an ointment is of prime importance if the finished product is expected to function as any one of the above categories. In the case of a protective ointment, it serves to protect the skin against moisture, air, sun rays and other external factors. It is necessary that the ointment neither penetrates the human skin barriers nor facilitates the absorption of substances through this barrier. An antiseptic ointment is used to destroy or inhibit the growth of bacteria. Frequently bacterial infections are deeply seated; a base which has the capacity to either penetrate or dissolve and release the medication effectively is therefore desired. Ointments used for their emollient effect should be easy to apply, be non-greasy and effectively penetrate the skin.

 

Ointment Bases

 There are five (5) classes or types of ointment bases which are differentiated on the basis of their physical composition. These are:

 oleaginous bases

 absorption bases

 water in oil emulsion bases

 oil in water emulsion bases

 water soluble or water miscible bases

 Each ointment base type has different physical characteristics and therapeutic uses based upon the nature of its components. The following table summarizes the composition, properties, and common uses of each of the five types. For more information consult Remington’s.

SUMMARY CHART: PROPERTIES OF OINTMENT BASES

	Oleaginous Ointment Bases	Absorption Ointment Bases	Water/Oil Emulsion Ointment Bases	Oil/Water Emulsion Ointment Bases	Water-miscible Ointment Bases
Composition	oleaginous compounds	oleaginous base + w/o surfactant	oleaginous base + water (< 45% w/w) + w/o surfactant (HLB <8)	oleaginous base + water (> 45% w/w) + o/w surfactant (HLB >9)	Polyethylene Glycols (PEGs)
Water Content	anhydrous	anhydrous	hydrous	hydrous	anhydrous, hydrous
Affinity for Water	hydrophobic	hydrophilic	hydrophilic	hydrophilic	hydrophilic
Spreadability	difficult	difficult	moderate to easy	easy	moderate to easy
Washability	nonwashable	nonwashable	non- or poorly washable	washable	washable
Stability	oils poor; hydrocarbons better	oils poor; hydrocarbons better	unstable, especially alkali soaps and natural colloids	unstable, especially alkali soaps and natural colloids; nonionics better	stable
Drug Incorporation Potential	solids or oils (oil solubles only)	solids, oils, and aqueous solutions (small amounts)	solids, oils, and aqueous solutions (small amounts)	solid and aqueous solutions (small amounts)	solid and aqueous solutions
Drug Release Potential*	poor	poor, but > oleaginous	fair to good	fair to good	good
Occlusiveness	yes	yes	sometimes	no	no
Uses	protectants, emollients (+/-), vehicles for hydrolyzable drugs	protectants, emollients (+/-), vehicles for aqueous solutions, solids, and non-hydrolyzable drugs	emollients, cleansing creams, vehicles for solid, liquid, or non-hydrolyzable drugs	emollients, vehicles for solid, liquid, or non-hydrolyzable drugs	drug vehicles
Examples	White Petrolatum, White Ointment	Hydrophilic Petrolatum, Anhydrous Lanolin, Aquabase™, Aquaphor®, Polysorb®	Cold Cream type, Hydrous Lanolin, Rose Water Ointment, Hydrocream™, Eucerin®, Nivea®	Hydrophilic Ointment, Dermabase™, Velvachol®, Unibase®	PEG Ointment, Polybase™

*Varies depending upon specific content of the ointment base and the relative polarity of the drug(s) incorporated. This table refers more generally to the release of a typical nonelectrolyte (primarily lipophilic) drug.

 

Preparation of Ointment Bases

Prepare 120 g of each of the following five ointments on a w/w basis. One partner should prepare bases #1, 3 and 5 while the other prepares #2 and 4. Make sure that you follow closely the procedures for preparation.

General Comments About Compounding Ointment Bases

Between 2 and 4 grams of an ointment may be lost in the compounding process. The ointment is lost as it adheres to beakers, ointment tiles, or ointment pads. To compensate for this loss, make an excess of the ointment. Some general rules might be to add 10% or 3 grams excess to the prescribed amount.

When heat is used to melt ingredients, use a water bath or special low temperature hotplate. Most ingredients used in ointment bases will liquefy around 70°C These two heating devices provide adequate control over the heating and will ensure that the ingredients are not over heated. A water bath will only heat to the boiling point of water which is 100°C. Special “low temperature” hotplates (full range is 25°C to 120°C) are not a standard laboratory type hotplate; those hotplates heat at 125°C to 150°C at their lowest setting.

When both an oil and aqueous phase are being mixed together to make an ointment, it is helpful to heat the aqueous phase a few degrees higher than the oil phase prior to mixing. The aqueous phase tends to cool faster than the oil phase and may cause premature solidification of some ingredients. However, use the lowest temperature possible and keep the time of heating as short as possible. This will minimize the quantity of water lost through evaporation.

 When melting a number of ingredients, melt the ingredient with the highest melting point first. Then gradually reduce the heat to melt the ingredient with the next lowest melting point. Continue this process until all ingredients have been added. This will ensure that the ingredients were exposed to the lowest possible temperature and thus enhance the stability of the final product.

The cooling step in an ointment’s preparation is an important part of the compounding process.

 Do not accelerate the cooling process by putting the melt in water or ice. This will change the consistency of the final product making it more stiff than desired.

If adding volatile ingredients such as oils, flavors, or drugs, add them when the product is “cool to the back of the hand.” The melt will still be fluid enough for adequate mixing but not hot enough to evaporate the ingredient.

Ointments should be cooled until just a few degrees above solidification before they are poured into tubes or jars. They should be thick, viscous fluids. This will minimize “layering” of the ointment in the packaging container. However, this is not the preferred method of packing an ointment tube or jar.

Most bases achieve their final consistency and texture several hours after they are compounded.

BASE NO. I: Oleaginous Base (White Ointment) White Wax 5%    ________ g

White Petrolatum  95%  ________ g

Procedure for Preparation:

Melt the white wax on a hot plate. No need to heat beyond 70 – 75°C

When the wax has completely melted, add the petrolatum and allow the entire mixture to remain on the hot plate until liquefied.

Following liquefication, remove from heat and allow the mixture to congeal. Stir the mixture until it begins to congeal.

BASE NO. II: Absorption Base Cholesterol        3%    ________ g

Stearyl Alcohol     3%    ________ g

White Wax   8%    ________ g

White Petrolatum  86%  ________ g

Procedure for Preparation:

Melt the stearyl alcohol, white wax, and petrolatum together on a hot plate.

Add the cholesterol to the mixture; stir until completely dissolved.

Remove the mixture from the hot plate and stir until congealed.

BASE NO. III: W/O Emulsion Base (Cold Cream type base) White wax  12.0%         ________ g        

Cetyl Esters Wax (or Spermaceti)     12.5%         ________ g        

Mineral Oil (Sp Gr = 0.9)         56.0%         ________ g         ________ ml

Sodium Borate      0.5% ________ g        

Water  19.0%         ________ g         ________ ml

Procedure for Preparation:

Melt the white wax and spermaceti on a hot plate.

Add the mineral oil to this mixture and bring the temperature to 70°C.

Dissolve the sodium borate in water.

Heat the sodium borate solution to 70°C.

When both phases have reached the desired temperature, remove both phases from the hot plate and add the aqueous phase slowly and with constant stirring to the oil phase.

Stir briskly and continuously until congealed.

BASE NO. IV: O/W Emulsion Base (Hydrophilic Ointment) Sodium Lauryl Sulfate  1.0%         ________ g        

Propylene Glycol (SP Gr = 1.035)     12.0%         ________ g         ________ ml

Stearyl Alcohol     25.0%         ________ g        

White Petrolatum  25.0%         ________ g        

Purified Water       37.0%         ________ g         ________ ml

Procedure for Preparation:

Melt the stearyl alcohol and white petrolatum on a hot plate.

Heat this mixture to 70°C.

Dissolve remaining ingredients in water and heat the solution to 70° C.

Add the oleaginous phase slowly to the aqueous phase, stirring constantly.

BASE NO. V: Water Soluble Base Polyethylene Glycol 400 (SP Gr = 1.12)      60%         ________ g         ________ ml

Polyethylene Glycol 3350        40%  ________ g        

Procedure for Preparation:

Melt the PEG 400 and Carbowax 3350 on a hot plate.

Warm the mixture to about 65°C.

Remove from the hot plate and stir until congealed.

 

How To Pack An Ointment Jar

Prepare the ointment. Select an ointment jar that will just hold all of the formulation.

  Begin by taking some ointment…

  … and fill the bottom of the ointment jar. Use the spatula to put ointment into the crevices.

  Continue adding ointment to the jar again using the spatula to put the ointment along the sides of the jar.

  As you fill the jar, stab the spatula into the ointment a couple of times. This will reveal air pockets that may have formed.

  Put the spatula halfway across the filled jar, and tilt in slightly. Rotate the jar…

  …and this is make a professional looking finish on the top of the ointment.

  Wipe off ointment from the threads of the jar.

  Cap the ointment jar.

 

Incorporation of Drugs into Ointment Bases

An ointment slab (left) and large metal spatulas should be used for this process. Ointment slabs are either ground glass plates or porcelain and provide a hard, nonabsorbable surface for mixing.

Ointment pads (right) have the advantage that “clean-up” is quicker, but the ointment can soak into the parchment paper. Further, the paper can absorb liquids and may tear when using sticky or thick ointments. Large metal spatulas are used instead of smaller metal spatulas because they have the proper combination of flexibility and strength for adequate shearing and mixing. Black rubber or plastic spatulas are not used in ointment compounding.

 

If preparing a large quantity of ointment, a mixing device of some type might be used instead of the ointment slab and spatula. Two options are an ointment mill, and an “electric mortar and pestle.” Ointment mills produce very smooth and elegant ointments. The electric mortar and pestle allows the formulation of the ointment and the dispensing of the formulation to be done in the same container.

 

 

Incorporating a Drug into an Ointment

The drug is usually the smaller quantity of the two ingredients. So geometric dilution will be used to “dilute” the smaller quantity drug into the ointment. The drug in this demonstration is Calamine (the pink powder).

  Add an amount of the ointment that is approximately equal in size to the Calamine.

  Spatulate the mixture.

  Add a second portion of the ointment to the spatulated mixture that is about the same size.

  Spatulate that mixture.

  Continue adding portion of the ointment to the spatulated mixture in approximately equal sizes until all of the ointment is used. Spatulate after each addition.

 

Oleaginous Bases

 To incorporate an insoluble drug into these bases, pulverize the powder on the pill tile or with a mortar and pestle (above/right). Use a levigating agent to wet the powder and then incorporate the wetted powder into the ointment base. Generally, the amount of drug to be incorporated into the ointment will be much less than the amount of ointment. In other words, a small amount of drug will be incorporated into a large amount of ointment. The process of geometric dilution will “diluted” the drug into the ointment. Geometric dilution involves a series of dilution steps. It begins by incorporating the drug into an amount of ointment of approximately the same size. Then a second amount of ointment approximately equal to the first mixture is added and mixed. This stepwise dilution process is continued all of the ointment has been used.

A good levigating agent is mineral oil since it is compatible with oleaginous bases. Sometimes using a small quantity of the base itself as the levigating agent is sufficient.

Soluble drugs can be incorporated into oleaginous bases by fusion. The base is liquefied over low heat (not to exceed 70°C) and then the drug is added to the molten base. The mixture is then allowed to cool with occasional stirring.

 Show how to incorporated a drug into an ointment using geometric dilution & 2 spatulas

 

Absorption Bases

An absorption base is an oleaginous base that contains a w/o emulsifying agent. When water is taken up into the base, it will form a w/o emulsion. Absorption bases typically can incorporate about 50% of their volume in water.

Incorporating insoluble drugs into these bases can be done mechanically or by fusion. The final destination (internal or external phase of the emulsion) of the drug must be considered when selecting a levigating agent. If the drug will reside in the internal phase (water phase), then the levigating agent should be water soluble or miscible. Water, glycerin, alcohol, or propylene glycol would be suitable levigating agents. If the drug will reside in the external phase, then mineral oil should be used.

Water soluble ingredients can be added to the water phase of the w/o emulsion. If the drug will dissolve in a small amount of water, the aqueous solution can be added directly to the base using a pill tile and spatula. If a larger quantity of water is needed to solubilize the drug or if an aqueous solution is being added to the base, heat may be needed to compound the formulation. It may be necessary to add additional emulsifier to the emulsion to accommodate the added water. Some commercial emulsions do have the necessary excess emulsifier.

 

W/O Emulsion Bases

 Oils and insoluble powders can be directly incorporated into the external phase using a pill tile and spatula. If a levigating agent is to be used with the insoluble powders, it should be miscible with the oil phase; mineral oil would be a suitable agent. Levigating agents may be needed with larger quantities of insoluble powders. If the insoluble powder has a different salt form that is oil soluble, consideration should be given to using that salt form.

The same comments that apply to incorporating water soluble ingredients into absorption bases also apply to w/o emulsion bases.

 

O/W Emulsion Bases

Water soluble powders can be directly incorporated into the external phase using a pill tile and spatula. If the powder is insoluble, the levigating agent should be water miscible so glycerin, propylene glycol, polyethylene glycol (PEG) 300 or 400, or alcohol would be acceptable. If the insoluble substance has a different salt form that is aqueous soluble, consideration should be given to using that salt form.

It may be more difficult to incorporate oil soluble ingredients into the o/w formulation. A small amount of oil can be incorporated into the base if there is excess emulsifier. Some commercial products do have the necessary excess emulsifier. If a larger portion of oil is to be added, the addition of more emulsifier may be necessary. If heat is used to incorporate the oil, it is important to work quickly so that water is not evaporated from the product. This will cause the product to become stiff and waxy.

 

Water Miscible Bases

Water soluble drugs can be dissolved in a small quantity of water and incorporated using a pill tile and spatula. Insoluble powders will require a water miscible levigating agent such as glycerin, propylene glycol, or polyethylene glycol 400. Oils can be added into these bases by first mixing the oil with glycerin or propylene glycol, and then incorporating the mixture into the base. Heat may be necessary if the quantity of liquid to add to the base is large.