Types of solutions

1. Honeys
•Honeys are thick liquid preparations used as vehicle instead of syrup.
•BPC lists two preparations containing honey.

- Oxymel, or (acid honey): Is a mixture of acetic acid (150 ml), purified water (150 ml), and honey (sufficient to produce 1000 ml of product

- Squill Oxymel: Contains squill, water, acetic acid and honey and is prepared by a maceration process.

2.Mucilage:

•Thick viscid, adhesive liquid produced by:

A-dispersing gum in water

B-extracting mucilaginous substances from vegetable substances.

•Mucilage are liable to decomposition & should used immediately unless a preservative is added.
•Acacia is prepared as (35% in water) & Tracaganth(6%) mucilage both contain benzoic acid as preservative.
•Mucilage are used as suspending agents. Examples include sulfur in lotions, and oils in emulsions.
•Synthetic agents as methylcellulose, polyvinyl alcohol and carboxymethylcellulose are used as mucilage substitutes.

Because synthetic gums are:
- Non glycogenic and may used in preparation of diabetic preparations.
- Stable at different pH
- Contain no oxidizing enzymes.

3. Jellies
•Jellies are a class of gels in which the structural coherent matrix contains a high portion of liquid, usually water.
•Prepared from acacia, gelatin and carboxymethylcellulose.
•Jellies are used as lubricants for surgical gloves, catheters, rectal thermometers and ultra-sonic devices. They are used as a base for topical contraceptive purpose.

Types Of Nonaqueous solution

1. Spirits: Spirits (essences), are alcoholic or hydro alcoholic solutions of volatile substance.

•Alcohol concentration usually over 60 %.
•Spirits used as flavoring agent and medicinally for the therapeutic value of the aromatic solute.
•Spirits may taken orally, applied externally, or used by inhalation
•When used orally, they are mixed with water to reduce the pungency of the spirit.
•Spirits should be stored in tight, light-resistant containers, and in a cool place. This prevents evaporations of either the alcohol or the active principle.

Incompatibilities of spirits:
•Spirit is of high concentration of alcohol so when mixed with water or with other aqueous solution, the volatile substance present in the spirits generally separated from solution and form a milky preparation.
•Spirit cause precipitation of salt from aqueous solution due to low solubility of salt in alcohol.

2. Collodions

•Are viscous liquid prepared by dissolving pyroxyline (nitrocellulose) (4%w / v) in a 3 : 1mixture of ether and alcohol.
•The resulting solution is highly volatile and flammable and should be stored in tight containers at temperature not more than 30 C remote from fire.
•They are applied to the skin by means of a soft brush and, when the ether and ethanol have evaporated, leave a protective film of pyroxyline on the surface.

Salicylic acid collodion USP:
•Contains 10% w/v of salicylic acid in flexible collodion USP.
•Used as a keratolytic agent in the treatment of corns and warts. They are water repellent protective for minor cuts and scratches.
•Collodion is made flexible by the addition of castor oil 3% or 2 % camphor.


3. Glycerins (Glycerites) Solution of drug in not less than 50% w/w glycerin.

•Highly viscous and have jelly-like consistency.
•Hygroscopic and should be stored in tightly closed containers.
•Phenol Glycerin BPC: Phenol.160 g, Glycerin840g.

•Procedure: Dissolve the phenol in the glycerin, Phenol Ear-drops BPC, Phenol glycerin40 ml, Glycerin, a sufficient quantity, to make... 100 ml

• Add the glycerin to the glycerites. Water should not be added to these preparations. It react with the phenol to produce a preparation which is caustic and, consequently, damaging the area of application.


•Starch glycerite: Emollient to the skin contains starch, benzoic acid, water & glycerin.


4.Liniments

•Are solutions or mixtures of various substances in oil, alcoholic solutions of soaps, or emulsionsand applied for external use with rubbing.( for muscle pain).
•The oil or soap base for ease of application and massage.
•Alcoholic Liniments are used generally for their rubefaciant, counterirritant, mildly astringent, and penetrating effects.
•Liniments should not be applied to broken skin.
•Calamine Lotion, Oily BPC (Calamine Liniment)

Nonaqueous solutions

                                         Nonaqueous solutions 

•Solution contains minor quantities of toxic nonaqueous solvents (acetone, benzene, petroleum ether).

•External nonaqueous solutions;

May contain ethanol, methanol, isopropyl alcohol, polyethylene glycols, various ethers or esters.

•Internal nonaqueous solutions;

May contain ethanol, glycol, propylene glycol certain oils, liquid paraffin or appreciable quantity of chloroform.

Non-aqueous solutions may be classified into4 groups;

nAlcoholic or hydro-alcoholic solutions;

•e.g., elixirs and spirits

nThe ethereal solutions;

•E.g., the collodions

nThe glycerin solutions;

•E.g., glycerites

nThe oleaginous;

•E.g., the liniments, medicated oils, oleo vitamins, sprays, and toothache drops.

1. Elixirs

Are clear, pleasantly flavored, sweetened hydro-alcoholic liquids intended for oral use.

nThey may medicated or non-medicated (vehicles) elixirs.

nThey are distinguished from other classes by presence of sugar and alcohol in the finished product.

nThe alcoholic content in Elixirs varies greatly (4 –40 %), from elixirs containing only a small quantity, to those that contain a considerable portion as a necessary aid to solubility.

nThe sweating agents used mainly sucrose and saccharin. 

nNon-medicated elixirs

•Aromatic Elixir USP 

–contains 21 to 23% ethanol and 31 % sugar.

•Compound Benzaldehyde Elixir NF

–contains 3 to 5 % ethanol.

•Medicated elixirs

Classifed according to their therapeutic use

•Antihistaminic elixir

–Chlorpheniramine maleate elixir usp

•Sedative elixir

–Phenobarbiton elixir

•Expectorant

–Terpine hydrate elixir NF

•Digestive elixir

–Pepsin elixir

•Incompatibilities of elixirs:

1-Alcohol in elixir precipitates tracaganth, acacia, agar and inorganic salts if added to aqueous solution.

2-if water is added to elixir, partial precipitation may occur due to insitu dilution of alcohol in the final preparation.

3-Elixir cause separation of extractive matter from tincture & fluid extract due to reduction of alcohol content.

Aqueous Solutions

I-Aqueous Solutions

nAqueous solutions are homogenous mixtures that are prepared by dissolving a solid, liquid or gas in an aqueous medium (vehicle; water, aromatic water, syrup or extracts).
1-Aromatic Water (medicated waters):It is clear saturated aqueous solution of volatile oils or other aromatic or volatile substances.

nTheir odors and tastes are similar to the volatile substances from which they are prepared.  

 nIt should be free from empyreumatic(smoke like) and other foreign odors.                          nUsed as flavored vehicles.
Aromatic water is prepared by one of 2 official methods:

A-Distillation (steam distillation):

nDrug :distiIIate ratio

 •For fresh drugs; From I: 2 to 2: l

 •For dried drugs:-e.g. cinnamon, anise and caraway (1:10)

 •For dried leaf drug:-e.g. peppermint (3:10 )

nMethod

 1.The drug is ground and mixed with sufficient quantity of purified H2O in the distillation unit.

2.After distillation,excess oil in the distillate is removed.

3.The drug shouldn't be exposed to direct heat, as the  distilled aromatic water may have the odor of  carbonized substance.

nIf the volatile principle in the water are delicate and present in small quantities (e.g., as in orange flower and rose waters), the distillate is returned several times to the still with fresh portions of flowers, thus, giving rise to the commercial terms double distilled, triple distilled, or quadruple distilled, according to the number of re-distillations. This process is called "Cohobation".

nStronger Rose Water NF is an example of aromatic water prepared by distillation.

B. Solution

nAromatic water may be prepared by repeatedly shaking 2 g or 2 ml of the volatile substance with 1000 ml of purified water.
nThe mixture is set aside for 12 hours, filtered through wetted filter paper, and made to volume (1000 ml) by adding purified water through the filter.
nThe system must be protected from light (dark amber color container).
e.g.,Chloroform Water:It is a saturated solution of chloroform, freshly prepared by dissolving 2.5 ml of chloroform in 1 liter of distilled water by vigorous shaking in well closed, dark colored bottle.
nIt is used as sedative in cough, asthma and colic mixtures and as vehicle.
Rose water;It is a clear saturated aqueous solution of rose oil prepared by distillation

nUsed for external preparations

Peppermint water:It is a clear saturated aqueous solution of peppermint oil.       
nUsed as carminative and antispasmodic                                                                                           
Disadvantages of aromatic water:                                             1.Deteriorate easily due to volatilization, decomposition or mold growth so they should be made in small quantities and protected from light and heat by storing in air tight and light resistant containers in a cool place.                                                                                                                      2. If soluble salt is added, it causes salting out of the oil (incompatibility) so to solve this problem part of aromatic water is replaced by purified water.          
N.B.The chemical composition of many of the natural volatile oils used in the preparation of pharmaceutical and cosmetics is now known. Therefore many synthetic substitutes are now available

2 -DOUCHES
Douche is an aqueous solution directed against a part or into a cavity of the body for cleansing or antiseptic actions.
nDouches may be dispensed in the form of a powder with directions for dissolving in a specified quantity of water (usually warm). However, tablets for preparing solutions are available (e.g., Dobell's Solution Tablets).
nIf powders or tablets are supplied, they must be free from insoluble material in order to produce a clear solution.
Dobell’s solution (Compound Na borate solution);
Sodium borate (Borax, sod. Tetraborate) is used in preparation of compound Na borate solution, in presence of water, sod.metaborate, boric acid and sod. hydroxid is formed
Na2B4O7 + 3 H2O 2 NaBO2+2H3BO3
NaBO2+ 2H2O Na OH + H3BO3
Dobell’s solutionhas been used as a nasal or pharyngeal douche.

 nAn eye douche                                                                                                                                  Used to remove foreign particles and discharges from the eyes                

   nPharyngeal Douches                                                                                                                     Are used to prepare the interior of the throat for an operation and cleanse it.             nVaginal douches                                                                                                                           Are the most common type of douche and used for cleansing the vagina and hygienic purposes.                                                                                                                                Ingredients vaginal douches.

1.Antimicrobial agent (benzalkonium chloride & parabens)
2.Astringent (ZnS04,potassium alum)
3.Anaesthetics (phenol & menthol)
4.Surface active agent (sod lauryl S04)
5.Substance to change pH (sod bicarbonate or citric acid)
3. Enema
•Enema preparations are rectal injections employed to evacuate the bowel (evacuation enema), systemic absorption, or to affect a local disease (Retention enema).

•Evacuation enema;
nUsually are given in quantities of 1 to 2 pt, at body temperature, and slowly injected by syringe.
nE.g. Sod. Phosphate enema USP
Each 100 ml of the enema contains
Dibasic sod. Phosphate heptahydrate6 gm
Monobasic sod. Phosphate monohydrate 16 gm
nE.g., Soap enema BPC
Soft soap 50 gm
Purified water to 1000 ml
•Retention enema;
nRetained in the intestine for systemic or local effect.
nShould not be used in large quantities than 150 ml for adult.
•Systemic effect enema (Microenema)
–Microenema; small volume preparation, vehicles used in formulation contains small quantities of alcohol or propylene glycol) E.g., aminophylline, indomethacin, valproic acid and metronidazol enemas.
•Local effect enema;
–E.g., Sulfasalazine rectal enema used for treatment of ulcerative colitis                                  –Barium sulfate enema contains 120 gm barium sulfate, 100 ml of acacia mucilage in starch enema to make 500 ml. Used for diagnostic purposes.
–Starch enema :A thin paste is made by triturating 30 g of powdered starch with200ml of cold water. Sufficient boiling water is added to make 1000ml. Starch enema may be used as soothing or as a vehicle for other forms of medication.
4. Gargles
•Gargles are aqueous solutions containing antiseptics, antibiotics, and or anesthetics. Used for treating the pharynx and nasopharynx by forcing air from the lungs through the gargle that is held in the throat then the gargle is expectorated.
•Many Gargles must be diluted with water prior to use.
E.g., Potassium chlorate and phenol gargle.
nContain pot. Chlorate-phenol diluted by 10 volume warm water before use & should be labeled to warn from swallowing.
 E.g., A flavored solution containing 7.5% povidone-iodine and 35% alcoholis available commercially as a mouth-wash or gargles  after suitable dilution.                    
5.Mouthwashes
•Mouthwashes are aqueous solution intended washout the mouth, used for two purposes, therapeutic and cosmetic.
Therapeutic Mouthwashes
•to reduce plaque, gingivitis, dental caries, and stomatitis.
Cosmetic Mouthwashes
•to reduce bad breath through the use of antimicrobial and or flavoring agents.
•Mouthwashes generally contain four groups of excipients:
nAlcohol
nSurfactants
nFlavors
nColoring agents
6. Juices
•A juice is prepared from fresh ripe fruit and is used in making syrups that are employed as vehicles.
nThe freshly expressed juice is preserved with benzoic acid and allowed to stand at room temperature for several days , until pectin that naturally are present are destroyed by enzymatic action, as indicated by the filtered juice yielding a clear solution with alcohol.
nPectin if allowed to retain, would cause precipitation in the final syrup.
•Cherry Juice and Raspberry Juiceare used as flavored vehicles.
•Artificial flavors now have been replaced many of the natural fruit juices. Although they lack the flavor of the natural juice, they are more stable and easier to incorporate into the final product.
7.Nasal solution
•Aqueous solution to be administrated to the nasal passages in drops or sprays for;
•Local effect e.g.;
nLocal sympathomimeticeffect such as Ephedrine Sulfate or Naphazoline.
nHydrochloride Nasal Solution USP to reduce nasal congestion
•systemic effect e.g.;
nLypressinNasal Solution USP and OxytocinNasal Solution USP and calcitoninnasal spray.
nPoorly GIT absorbed Drugs; gentamycin
nDrug that are inactivated in the GIT; Insulin
•The aqueous nasal solutions usually are isotonic and slightly buffered to maintain a pH of 5.5 to 6.5. In addition, antimicrobial preservatives and stabilizers, if required, are included in the formulation.
•A formula for Ephedrine Nasal Drops is:
Ephedrine Hydrochloride 0.5g
Chlorobutanol0.5g
Sodium Chloride0.5g
Water for preparations to 100 ml
8.Otic solution
Aqueous solution for topical administration to ear.
•The main classes of drugs used for topical administration to the ear include;
nAnalgesics, e.g., benzoicaine
nAntibiotics; e.g., neomycin
nAnti-inflammatory agents e.g., cortisone.
•The main solvents used include;
nWater and or Viscous liquids like glycerin or propylene glycol
•permit drug to remain in the ear for long time
•Hygroscopic so remove water from the tissue & reduce swelling.)
•To remove cerumen (ear wax) (alone or with propylene glycol and SAA)
•The patient should remain on his side for few minutes otherwise the drop run out of the ear.
•Sodium Bicarbonate Ear-Drops BP may be used if wax is to be removed from the ear.
 R / Sod. bicarbonate 5gm
Glycerin 33 ml
Water to 100 ml
9.Sweet and other viscid aqueous solutions
•These preparations include syrups, mucilages, honeys and jellies.
•Sweetness & viscosity is given by
1-Sugars
2-Polyols
3-Polysaccharide (gums)

Syrups

                                                      Syrups

. Syrups

•Concentrated solution of sugar (e.g. sucrose) in water or other aqueous liquid.

•Types of syrup:

1-Simple syrup; when water is used alone.

2-Medicated syrup;contain drug

3-Flavored syrup; contain no drug but aromatic or flavored substance

nFlavored syrup are accepted by both children and adults, and used as vehicles (e.g., Glycyrrhiza syrup and Raspberry Syrup BP 1988 )for masking the salty taste of bromide, iodides, and chlorides and bitterness of preparation containing B-complex vitamins.

•Glycerin or sorbitol (polyols) may be added to:

1. Prevent crystallization of sucrose.

2. Increase the solubility of other drugs.

•Alcohol is included to act as:

1-Preservative

2-Solvent for the flavors.

•Sucrose and Non-sucrose based syrup

nGlycogenic substances (materials converted to glucose in the body),

•Sucrose is the sugar most frequently used in syrup, called nutritive syrup due to the high calories content.

•Non-sugar as glycerin, propylene glycol and sorbitol

nNon-glycogenic substances

•These materials not hydrolyzed into the body and result in an excellent syrup -like vehicle for medication intended for use by diabetic patients 

•Such as methylcellulose and hydroxymethylcellulose.

•Saccharine sodium

•Cyclomate sodium

•These syrups called non-nutritive syrup.

•Most syrup contain high % of sucrose, usually 60 –80 %, not only for sweetness and viscosity but also for the syrup stability. Where diluted sugar solution are susceptible for microbial growth, saturated syrups are susceptible for crystallization of sucrose on cooling.

•Simple syrup is prepared by dissolving 85 gm sucrose in enough purified water to 100 ml of syrup.

nSimple syrup has specific gravity of about 1.313. Because the 85 gm sucrose are present, the difference between 85 gm and 131.3 gm or 46.3 gm represents the weight of water used in dissolving the 85 gm sucrose. The solubility of sucrose in water is 1 gm in 0,5 ml water. So the amount required to dissolve 85 gm sucrose is 42.5 ml. thus, only a very slight amount of excess water(3.8 ml /100 ml syrup) which is unsuitable for microbial growth. 

Ointments

           Ointments

Ointments are semi-solid preparations meant for external application to the skin or mucous membrane. The ointments are mainly used as protective emollient for the skin. They may also be used as vehicles or bases for the topical application of medicinal substances which is dissolved or suspended or emulsified in the base.
Character of ideal ointment

1- chemically and physically stable

2- smooth and free from grittiness

3- melt of soften at body temperature and be easily applied

4- the base should be non irritating and have no therapeutic action

5- the medicament should be finely divided and uniformly distributed inside the base.
Classification of ointments

Can be classified according to:

1- Therapeutic properties based on penetration.

2- Therapeutic uses.
therapeutic Classification according to -Ibased on penetration: properties
1-Epidermic

Not absorbed and Produce their action on the surface of skin.
2- Endodermic

Partially absorbed and release medicament that penetrate into the skin.
3-Diadermic 

Intended to release medicament that pass through the skin and produce systemic effect.
IIClassification according to therapeuticuses:

1-Antieczematous

Remove oozing and excretion for skin.

Contain hydrocorisone, coal tar and icthamol

2- Antibiotic oint

Used to kill microorganism.

Contain tetracycline, neomycin,bacitracin and quaternary ammonium compounds.
3-Antifungal oint.

Used to inhibit or kill fungi. Contain antifungal agents
4- Anti inflammatory oint

Used to inflammatory allergic conditions

Contain corticosteroidds such as hydrocortisone, betamethasone.
5-Antipruitic oint.

Relieve itching, contain benzocaine and coal tar
6-Astringent oint.

They cause the contarction of skin and decrease discharge

Contain calamine, zinc oxide and tannic acid.
7-counter irritant oint

Applied locally to irritate intact skin thus reducing or relive another irritation or deep pain.
 8-Ointment for treatment dandruff

Contain salicylic acid, cetrimide.
9-Emollients

Used to soften the skin, they include soft paraffin, cold cream,W/O emulsion.
10-Keratolytic and keratoplastic oint.

remove or soften the horny layer of the

Keratolytic:skin, they contain material such as resorcinol, salicylic acid and sulphur. increase the thickness of the horny

Keratoplastic: layer of the skin.
ex. Coal tar oint.
11-Parasiticde oint.

Inhibit or destroy living infestation such as lice and ticks. They contain sulphur, benzyl benzoate and gamma benzene hexachloride.
12-Protectant oint.

Protect skin from moisture, air, sun rays, or chemicals. They contain silicon, calamine, zinc oxide, titanium dioxide.

Stability of emulsions

                           Stability of emulsions

•A stable emulsion may be defined as a system in which the globules retain their initial character and remain uniformly distributed throughout the continuous phase.
•The three major phenomena associated with physical stability are
(1) The upward or downward movement of dispersed droplets relative to the continuous phase, termed Creaming or sedimentation, respectively
(2) The aggregation and possible coalescence of the dispersed droplets to reform the separate, bulk phases, termed cracking,
(3) Inversion, in which an o/w emulsion invert to become a     w/o emulsion, and vice versa.
1-Creaming:

nCreaming is the separation of an emulsion into two regions one of which is richer in the disperse phase than the other.

 E.g., creaming of milk when fat globules slowly rise to the top, of the product.

nThis is not a serious instability problem as a uniform dispersion can be obtained simply by shaking the emulsion,
nCreaming is undesirable from a pharmaceutical point of view because;
•Creamed emulsion is inelegant in appearance and provides the possibility of inaccurate dosage
•Increases coalescence possibility since the globules are close together in the cream.
•These factors are indicated by Stokes' law as follows:

V = d2(p –po) g / 18 ηo

where V is the velocity of creaming, d the globule diameter, P-Pothe densities of disperse phase and dispersion medium respectively and ηothe viscosity of the dispersion medium.

•A consideration of this equation shows that the rate of creaming will be decreased:

1-by reduction in the globule size.

2-a decrease in the density difference between the two phases, and

3-an increase in the viscosity of the continuous phase.

•This may ,be achieved by

nReduce the globule size
nIncreasing the viscosity of the continuous phase by the use of thickening agents such as Tragacanth or methylcellulose.
It is seldom possible to satisfactorily adjust the densities of the two phases.
2-Cracking or breaking( Coalescence):

Cracking is the coalescence of dispersed globules and separation of the disperse phase as a separate layer. It is an irreversible process and redispersion cannot be achieved by shaking.

•Factors that cause an emulsion to crack are:

1-The addition of chemical that is incompatible with the emulsifying agent, thus destroying its emulsifying ability.

Examples include surface-active agents of opposite ionic charge, e.g. the addition of cetrimide (cationic) to an emulsion stabilized with sodium oleate (anionic).

2-Bacterial growth: protein materials and non-ionic surface-active agents are excellent media for bacterial growth.
3-Temperature change:

nheating above 70°C destroys most emulsions.
nprotein emulsifying agents may be denaturated 
nthe solubility of non-ionic emulsifying agent change with a rise in temperature
nFreezing will also crack an emulsion; this may be due to the ice formed disrupting the interfacial film around the droplets.
3-Phase inversion:
•Soaps of divalent metals produce w/o emulsions while soaps of monovalent metals (and ammonium soaps) produce o/w emulsions. 
•An o/w emulsion stabilized with sodium stearate can be inverted to the w/o type by adding calcium chloride to form calcium stearate (phase inversion).

                                                  

Methods of emulsion preparation

   Methods of emulsion preparation

There are two methods of preparing a primary emulsion:

1-Dry gum method:-

Emulsifier (acacia) is mixed with oil before water addition.

•The quantities of oil, water and gum for primary emulsion are calculated. The acacia and the oil are placed in a dry porcelain mortar. When the acacia is thoroughly distributed throughout the oil, Water is added, all at once. The mixture is triturated continuously but lightly in one direction until the mixture thickens under the pestle.
•The primary emulsion is triturated for at least 5 minutes. Finally, the emulsion is transferred to a graduated cylinder and brought to volume with water. The emulsion should be Labeled "Shake well before use.
2-Wet gum method:

Emulsifier is added to water to form a mucilage then oil is slowly added to emulsion.

nThequantitiesofoil,waterandgumforprimaryemulsionarecalculated.Acaciaandwateraretrituratedtoformmucilageinaporcelainmortar.TheoilisaddedinSmallamountswithconstant,rapidandlighttrituration.Whenalltheoilhasbeenadded,themixtureistrituratedvigorouslyforafewminutes.Finally,theemulsionistransferredtograduatedcylinderandbroughttovolumewithwater.
•Emulsions containing more than one oily liquid:

nWhen two or more oily liquids are present, the quantity of acacia required for each is calculated, and the sum of these quantities is used for the emulsion. Alternatively each oil may be emulsified separately before mixing.

•Emulsions containing water-soluble substances:

nMost of the substances included in emulsions are water-soluble, e.g. salts, syrups, glycerin. Water-soluble substances are dissolved in the aqueous vehicle required for the approximate completion of the desired volume in this way are used in a dilute state as possible because some substances have "de -emulsifying" properties, i.e. they might unstabilize the emulsion if added in concentrated solution.
•Emulsions containing oil-soluble substances:

nE.g.,Salol and naphthol
nEmulsion containing oil-soluble substances, should be prepared with 50 % more Gum than required for other emulsions. The oil-soluble substances are dissolved in the Oil before preparing the primary emulsion.
•Emulsions containing substances insoluble in either oil or water
nThese substances must be finely powdered in a mortar, and mixed with the acacia required for the primary emulsion. The oil is then added, and the primary emulsion prepared in the usual way.
nExample: Bismuth carbonate in a castor-oil emulsion, and phenolphthalein in a liquid paraffin emulsion.
•Emulsions containing a small proportion of oily substances:
nIf the proportion of oil is too small, modifications must be made. Acacia emulsions containing less than 10% oil tend to cream readily. An inert oil, such as arachis oil, should be added to increase the amount of oil to 10 -20%, and so prevent this from happening.

Suspension

                                           Suspension                                                                          

A coarse suspension is a dispersion of finely divided, insoluble solid particles (the disperse phase)in a fluid (the dispersion medium).

•Most pharmaceutical suspensions consist of an aqueous dispersion medium although in some instances it may be an organic or oily liquid.
•Physical properties, of a well-formulated suspension:
1)Thesuspensionmustremainsufficientlyhomogenousforatleasttheperiodbetween
shakingthecontainerandremovingtherequireddose.
2)Thesedimentproducedonstoragemustbeeasilyresuspendedbytheuseofmoderateagitation.
3)Thesuspensionmayberequiredtobethickenedinordertoreducetherateofsettlingoftheparticles.Theviscositymustnotbesohighthatremovaloftheproductfromthecontainerandtransfertothesiteofapplicationisdifficult.
4)Thesuspendedparticlesshouldbesmallanduniformlysizedinordertogiveasmooth,elegantproductfreefromagrittytexture.
Pharmaceutical applications of suspensions:

•Suspensions can be used as

1 -Oral suspensions

2 –Reconstitutable suspensions.

3 -Parenteral suspensions.

4-Topical and cosmetic suspensions.

5-Aerosol suspensions.
1. Suspensions as oral drug delivery systems

Many people have difficulty in swallowing solid dosage forms and therefore require the drug to be dispersed in a liquid. Some materials are required to be present in the gastrointestinal tract in a finely divided forms, and their formulations as suspensions will provide the desired high surface area. Solids such as kaolin, magnesium carbonate and magnesium trisilicate, for example, are used for the adsorption of toxins, or to neutralize excess acidity.

The taste of most drugs is more noticeable if it is in an insoluble form. Paracetamol is available both in solution as pediatric paracetamol Oral Solution and also as a suspension. The latter is more palatable, and therefore particularly suitable for children.

2. Suspensions for topical
administration

They can be fluid preparations, such as Calamine Lotion, which are designed to leave a light deposit of the active agent on the skin after quick evaporation of the dispersion medium.

Some suspensions, such as pastes, are semisolid in consistency and contain high concentrations of powders dispersed-usually-in a paraffin base. It may also be possible to suspend a powdered drug in an emulsion base, as in Zinc Cream.
3-Parenteral suspension

Parenteral suspension used for

•Control the rate absorption the drug.

nBy varying the size of he dispersed particles of active agent, the duration of activity can be controlled. If the drug is suspended in a fixed oil such as arachis or sesame, the product will remain after injection in the form of an oil globule, thereby presenting to the tissue fluid a small surface area from which the partitioning of drug can occur. The release of drug suspended in an aqueous vehicle will be faster.

4 –Reconstitutable suspensions.

reach user as a mixture of dry powders dispersed in vehicle (usually water) i.e., reconstituted immediately before use.

nOnce reconstituted, they have limited shelf-lives (weeks)
nUsed for unstable drugs.
nE.g. Dry powder of pediatric antibiotics can stay for long shelf-life, but when formulated as suspension used for 15 days.
5-Suspensions for inhalation
nFor drugs unstable in GIT
nRapid therapeutic effect
nNo first pass metabolism
nLow doses (few side effects)
 

Emulsions

                                                                    Emulsions

An emulsion is thermodynamically unstable system consists of two immiscible liquids, one of which is dispersed as globules (dispersed phase) in the other liquid phase (the continuous phase).

•The system is stabilized by the presence of an emulsifying agent. •The dispersed liquid or internal phase usually consists of globules of diameters between 0.5 and 25 um, which are distributed within the external or continuous phase.
•The consistency of emulsion system ranged from a mobile liquid to semisolid.

•Types of emulsion;

1-Water in oil w/o

(water globules dispersed in oil phase)

2-Oil in water o /w :

(oil droplets dispersed in water)

3-Multiple emulsion w /o /w or o/w/o

4-Micro emulsion;the dispersed globules (1 nm to 0.5 um diameter), the preparation, is transparent.

•Phase-volume ratio:

is the volume of the internal phase compared with that of the external phase. The most stable emulsions have an internal phase occupying between 40 to 60 % and not more than 74% of the total volume of an emulsion.

Pharmaceutical applications of emulsions:

Emulsions have a wide range of uses, including:

1. Oral emulsions (o/w emulsion);

nTo enhance palatability
nTo increase absorption of oils and oil-soluble drugs through intestinal walls. E.g., griseofulvin suspended in oil in an o/w emulsion.
2. Intramuscular injections (w/o emulsion)
ne.g., water-soluble vaccines to provide slow release and therefore a greater antibody response and longer-lasting immunity (depot therapy) .
3. Intravenousinjections (o / w emulsifier).
nemulsions are used to deliver oily nutrients intravenously to patients, using non-toxic emulsifying agents, such as lecithin
nOnly a few emulsifying agents, E.g. lecithin, gelatin, serum albumin, methyl cellulose and polysorbate 80 (Tween 80) are used for I.V o/w emulsions.

nThe globule size must be kept below 1um to avoid the formation of emboli.

4. Topical application

Emulsions for external use are o/w or w/o,

nThe o / w emulsions are less greasy, easily washed off the skin and more cosmetically acceptable than w/o emulsions.
nThe w/o emulsions, have an emollient effect, which hydrates upper layers of skin.

Emulsifying agents:

•If the emulsifying agent is more soluble in water i.e. Hydrophilic, then water will be the continuous phase and an o/w emulsion will be formed. If the emulsifying agent is more soluble in oil, i.e. lipophilic, then oil will be the continuous phase and a w/o emulsion will be formed.
•The o/w emulsion requires hydrophilic emulsifiers with HLB 8 -18.
•The w/o emulsion requires lipophilic Emulsifiers with HLB 3 -6.
A-o/w emulsifying agents:

1-Monovalent soaps such as sodium oleate. it has HLB value of 18

2-Polyoxyethylene sorbitan mono-oleate (polysorbate 80 or Tween 80). It is hydrophilic nonionic surface-active agent has HLB value of 15.

3-Acacia (salts of d-glucuronic acid).It is hydrophilic colloid has HLB value of 8.

4-Tragacanth (polysaccharide).It has HLB value of 13.2.

5-gelatin (polypeptide and amino acids). It is hydrophilic colloid with HLB value of 9.8

6-Triethanolamineoleate .It is anionic surface active agent has HLB value of 12.

7-lecithin (phospholipid). It is the chief emulsifier In egg yolk.

8-Bentonite (hydrated aluminum silicate). It is solid particles.
B-w/o emulsifying agent:

1-Polyvalent soaps such as calcium plamitate. .

2-Span 80. It is lipophilic nonionic surface active agent has HLB value of 4.3.

3-Cholesterol.

4-Woolfat.  

Formulation of emulsions

            Formulation of emulsions

1.Formulation by the method of HLB

(hydrophile-Lipophile Balance);

•Surface-active agents are amphiphiles in which the molecule or ion contains both hydrophilic and lipophilic portions.

•Griffen developed a scale based on the balance between these two opposing tendencies. This so called HLB scale.

nA numerical scale, extending from 1 to 50.

nThe more hydrophilic surfactant have high HLB numbers (in excess of 10),

nsurfactants with HLB numbers from 1 to 10 considered to be lipophilic.

•the type of emulsion is related to the balance between hydrophilic and lipophilic solution tendencies of the surface-active emulsifying agent.

•Surfactants with a proper balance in their hydrophilic and lipophilic affinities are effective emulsifying agents since they tend to concentrate at the oil / water interface.
•The relationship between HLB values and the application of the surface active agent is shown in the table

HLB      Pharmaceutical use

0 –3       Antifoaming

4 –6       w/o emulsifier

7 –9       Wetting agent

8 –18     o/w emulsifier

13 –15   Detergent

10 -18    Solubilizer

•If the HLB of the oil phase is known and the type of emulsion desired is known (o/w or w/o), the formulator chooses two emulsifying agents, one with an HLB value above and the second with an HLB value below ,that required by the oil. These are blended to give a mixture of the correct HLB. The following formula, should serve as an example.

•R/

Liquid petrolatum (HLB 10.5) 50 gm

Emulsifying agent 5 gm

Span 80 (HLB 4.3)

Tween 80 (HLB 15)

Water,Q.S 100 ml

Prepare o/w emulsion

•Calculation

Tween 80 (HLB 15)     6.2 parts

Required HLB =10.5

Span 80 (HLB 4.3)      4.5 parts

10.7 parts
•The required weight of tween = 5*6.2/10.7=2.9 gm

•The required weight of span = 5*4.5/10.7=2.1 gm

Preparation

•The oil soluble span is dissolved in oil and heated to 75 C,

•The water soluble tween is added to the aqueous phase, which is heated to 70 C.

•Mix the oil phase with the aqueous phase and stirred until cool.
•Formulation additives:

1-Antioxidants

2-Preservatives

3-Humectants

4-Colors and flavorings.

1-Antioxidants:

•Some oils are liable to degradation by oxidation and therefore antioxidants may be added to the formulation. They should be preferentially soluble in the oily phase. Antioxidants used in oral emulsions which are odorless and tasteless include ascorbic acid, citric acid, sodium metabisulphite and sodium sulphite.

•Antioxidant is commonly used at concentrations ranging from 0.001 to 0.1%.
2-Preservatives:

•Emulsions contain water, which will support microbial growth. Microbes produce unpleasant odors, color changes and gases, pH change and breakdown of the emulsion

•Microbial growth normally occurs in the aqueous phase of an emulsion, therefore it is important that a sufficient concentration of preservative is, present in the aqueous phase.

•Some preservatives in use are listed below:

nMethylparahydroxybenzoate in 0.2% & Propyl parahydroxybezoate in 0.02%. ,They are suitable for both external and internal use.

nBenzoic acid, which is effective at a concentration of 0.1% at pH below 5.

nChloroform, as chloroform water (0.25% v/v).

nChlorocresol (0.1 %).
3-Humectants:

nTo reduce the evaporation of the water either from the packaged product when the closure is removed or from the surface of the skin after application.

nE.g., Propylene glycol, glycerol and sorbitol at a concentration around 5%.

4-Colours and flavourings:

nColour is rarely needed in an emulsion, as most have an elegant white colour and thick texture.

nEmulsions for oral use will usually contain some flavouring agent.
Example of emulsion formulations

R/

Code liver oil 30 ml

Chloroform 0.2 ml

Cinnamon water to 100 ml

•Prepare 100 ml cod liver oil emulsion (o/w emulsion for internal use)

•Formulation

nCod liver oil is a fixed oil that requires the addition of acacia gum as an o/w emulsifying agent

nPreparation of primary emulsion

0 w G

4 2 1

30 ml 15ml 7.5 g

nTherefore 30 ml cod liver oil, 15 ml of cinnamon water and 7.5 g of acacia gum will be used to prepare the primary emulsion. Cinnamon water acts as a flavouring agent and vehicle. .chloroform is dense only slowly soluble and act as a preservative.