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Pharmacopoeieal Preparations

 


Syllabus:
Principles and methods of preparation of aromatic waters, spirits, elixirs, glycerin, linctus, solutions, milk and magmas, mucilages and special preparations like pyroxylins and flexible collodions.
 


Reference Books:
1.      Cooper & Gunn’s Dispensing for Pharmaceutical Students by S.J. Carter.
2.      Dispensing Pharmacy by R.M. Mehta
3.      Pharmaceutics-II by R.M. Mehta
4.      Pharmaceutics-II by A.K. Gupta
5.      Indian Pharmacopoeia, 2nd Edn. 1966
 


AROMATIC WATERS

Definition:
Aromatic waters are clear, saturated solutions of aromatic substances (may be volatile oils or volatile solids) in water. Their flavors and taste are similar to the corresponding aromatic substances used.
Use:
(i)     They are mainly used as the vehicle for oral liquid preparations due to their flavoring properties. E.g. Peppermint Water  IP.
(ii)   Some aromatic waters have preservative action, hence are used as menstruum to extract crude drugs. E.g. Chloroform Water IP.
(iii) Some aromatic waters have mild therapeutic action. E.g. Camphor Water IP has carminative action, Anise Water has carminative and mild expectorant action.

Methods of Preparations

(a)    Solution method
(i)          The volatile oil is shaken with 500 times its volume of Purified Water IP.
(ii)        The mixture is shaken for a period of 30 minutes.
(iii)      The mixture is set aside for 12 hours or overnight.
(iv)       Filtered.
(b)   Using distributing agents
(i)          The volatile oil is triturated with a sufficient quantity of powdered talc or kieselghur, or pulped filter paper in a mortar.
(ii)        Purified Water IP 500 times the volume of oil is taken and mixed.
(iii)      The solution is filtered.

N.B. Talc, kieselghur, pulp of filter paper are called distributing agents. The volatile oils get adsorbed on the particle surface and a large surface area helps in quick dissolution of the oil into water.

(c)    Dilution from cnocentrated preparations
(i)          A concentrated aromatic water is prepared as per the formula given in the pharmacopoeia.
(ii)        One ml of concentrated aromatic water is diluted with 39 ml of Purified Water IP and mixed.

Examples of various Aromatic Waters

Name of Aromatic Water
Name of Concentrated Aromatic Water
Dilution
Use
Conc. Arom. Water
Purified Water
Anise Water
Concentrated Anise Water
1ml
39ml
Flavor, Carminative, Mild expectorant
Camphor Water
Concentrated Camphor Water
1ml
39ml
Flavor, Carminative, Mild expectorant
Caraway Water
Concentrated Caraway Water
1ml
39ml
Flavor, Carminative
Chloroform Water
Chloroform Water Double Strength (DS)
1ml
39ml
Preservative, Flavor
Cinnamon Water
Concentrated Cinnamon Water
1ml
39ml
Flavor, Carminative
Dil Water
Concentrated Dil Water
1ml
39ml
Flavor, Carminative (particularly for infants in gripe water)
Peppermint Water
Concentrated Peppermint Water
1ml
39ml
Flavor, Carminative, Weak Preservative
Formulae of different aromatic waters available in IP 1966
Name of the Aromatic water
Formula
Method of preparation
Chloroform Water IP66
Chloroform 2.5 ml
Purified water upto 1000ml
Solution method.
Camphor Water IP66
Camphor 1gm
Alcohol (90%v/v)
Purified Water 1000ml
Camphor is dissolved in alcohol and the alcoholic solution is added to purified water drop-wise. The mixture is shaken well. N.B. Water should not be added to the alcoholic solution.
Concentrated Peppermint Water BPC
Peppermint oil 20ml
Alcohol (90%v/v) 600ml
Purified Water upto 1000ml
Peppermint oil is dissolved in alcohol. Purified water is added in small amount to the alcoholic solution and shaken vigorously. Suitable amount of talc is dispersed in the solution to adsorb the excess oils. Finally the solution is filtered.

SPIRITS

Definition:
Spirits are alcoholic or hydroalcoholic solutions of volatile substances. Most are used as flavoring agents but a few have medicinal value. The active ingredient in the spirit may be a solid, liquid or gas.
Use:
(i)     They are mainly used as flavoring agents. e.g. Lemon spirit, Peppermint Spirit, Compound Orange Spirit etc.
(ii)   Some spirits are taken internally for their medicinal value e.g. Aromatic Spirit of Ammonia IP is a respiratory stimulant.
Storage:
Spirits contains volatile substances hence, should be stored in tight containers and should be stored in a cool place. This prevents the volatilization of alcohol or the active substances.
Methods of preparation:
(i)    Simple solution method
       e.g. Chloroform Spirit IP
                      Spirit of Ether IP
(ii) Solution with maceration
      e.g. Compound Orange Spirit IP
(iii) Distillation
       e.g. Aromatic Spirit of Ammonia IP

Examples:
Name of Spirit
Formula
Method of preparation
Chloroform Spirit IP
Chloroform 50ml
Alcohol (90%v/v) upto 1000ml
Simple solution
Spirit of Ether IP
Anaesthetic Ether 330ml
Alcohol (90%v/v) up to 1000ml
Simple solution

Aromatic Spirit of Ammonia

Synonym.  Aromat. Sp. Ammon.,   Spirit of Sal Volatile
Formula:              Ammonium bicarbonate [NH4HCO3]           25g
                              Ammonia solution strong                                             70ml
                              Lemon oil                                                         5ml
                              Nutmeg oil                                                        3ml
                              Alcohol (90%v/v)                                           750ml
                              Purified Water q.s.                                          1000ml
Method of preparation:
(i)     Lemon oil (5ml) + Nutmeg oil (3ml) + Alcohol 90% (750ml) + Purified Water (375ml) ® taken in a still (1173ml)
(ii)   The first 875ml portion of the distillate is collected.
(iii) The second 35ml portion of the distillate is collected separately.
(iv)  The second distillate is taken in a bottle, ammoniumbicarbonate (25g) and strong ammonia solution (70ml) is taken. The bottle is closed and warmed gently at 600C on a water bath. The bottle is shaken to dissolve the salt completely.
(v)   The solution is cooled and filtered through cotton wool.
(vi)  This solution is then mixed gradually with the first distillate (i.e. 875ml).
(vii)          Sufficient purified water is added to make up the volume up to 1000ml.

Storage:
The preparation contains volatile oils (Nutmeg and Lemon oil) therefore, it should be stored in a tightly closed container in a cool place.


N.B.
·        Nutmeg oil contains both volatile oil and non-volatile resinous substances. This resinous matter makes the solution dark during storage. Hence, by distillation method only the volatile part is separated out.
·        First distillate contains mainly alcohol and the aromatic part of the volatile oils. Since it contains the volatile parts hence, it is not heated.
·        The second distillate mainly contains water. Ammonium bicarbonate is not soluble in alcohol so it is dissolved in the second distillate (aqueous).
·        Ammonium carbonate decomposes in water to produce NH3, CO2 and H2O. To reduce this decomposition strong ammonia solution is added.
 



TINCTURES

Definition:
Tinctures are alcoholic or hydroalcoholic solutions usually containing dilute concentration of active principles of vegetable or animal drugs.
Methods of preparation:  They are commonly prepared by maceration or by percolation process.
N.B. Most tinctures of vegetable drugs represents the extractive from 20g of the drug in 100ml of tincture.

Examples:
Name of the preparation
Uses
Reference IP 1966 (page no.)
Aconite Tincture IP
Belladonna Tincture IP
Capsicum Tincture IP
Compound Cardamom Tincture IP
Compound Cinchona Tincture IP
Datura Tincture IP
Digitalis Tincture IP
Strong Ginger Tincture IP
Hyoscyamus Tincture IP
Ipecacuanha Tincture IP
Nux Vomica Tincture IP
Opium Tincture IP
Camphorated Opium Tincture IP
Orange Tincture IP
Compound Picrorhiza Tincture IP
Stramonium Tincture IP
Urginea Tincture IP
Valerian Ammoniated Tincture IP
Analgesic, cardiac depressant
Parasympatholytic
Carminative
Carminative
Antimalarial
Parasympatholytic
Cardiotonic
Carminative
Parasympatholytic
Expectorant and Emetic
Bitter stomachic
Hypnotic, sedative
Hypnotic, sedative
Flavoring Agent
Bitter stomachic
Parasympatholytic
Cardiotonic, expectorant
Sedative

93
147
155
189
226
239
315
343
374
444
503
504
505
565
699
787
792

ELIXIRS

Definition:
Elixirs are clear, liquid, oral preparations of potent drugs (like antibiotics, antihistaminics, sedatives etc.) or unpalatable drugs. They are pleasantly flavoured and usually attractively colored.
N.B. Elixirs are clear preparations, but mixtures are often not clear due to the presence of fine droplets of volatile oils present in it.
Examples:
Name of the preparation
Uses
Reference IP 1966 (page no.)
Elixir of Vitriol IP
Piperazine Citrate Elixir IP
Simple Elixir IP
Terpin hydrate Elixir IP
Pharmaceutical aid
Anthelmintic
Pharmaceutical aid
Expectorant
726
568
656
736
Formulation:
Vehicles
Vehicle is the main part of the preparation that carries the drug.
·        Production of a clear solution: Flavoring agents containing essential oils or precipitates from plant extract may produce faint cloudiness. To keep the essential oils in solution state 10 – 20% of alcohol is added. Glycerol (i.e. glycerin) is added to keep the essential oil in to solution and to dissolve some ingredients of plant extracts like tannins and their oxidation products.
·        Solution of medicament of low water solubility: If the drug is not completely soluble in water then a mixed solvent is used to dissolve the drug (i.e. medicament). E.g. phenobarbitone is dissolved in alcohol, glycerol and water, paracetamol is dissolved in alcohol, propylene glycol and glycerol.
N.B. Alcohol is avoided in paediatric elixirs hence in paediatric Paracetamol Elixir propylene glycol is used as the main solvent.
·        Production of a palatable preparation: The vehicle of many elixir is syrup or a flavored syrup.
Adjuncts
Chemical Stabilizers: Some special chemicals are required to make the elixir stable.
e.g. Citirc acid, disodium edetate etc.
Coloring agents: Many elixirs are attractively colored by coal tar dyes.
e.g. Amaranth (magenta red), Compound Tartrazine (saffron), Green S and Tartrazine (Green).
Flavoring agents: Sweetening agents and fruit flavors are used.
Sweetening agents: e.g. Plain and flavored sucrose syrup, glycerol, sorbitol, invert syrup and saccharin sodium.
Fruit flavor: Blackcurrant syrup (to mask bitter taste of drug), Raspberry Syrup (to mask bitter taste of drug), Compound Orange Syrup (to mask sour and bitter taste of drugs).
Preservatives: To reduce the mould growth and fermentation preservatives are added.
·        Vehicle containing 20%v/v alcohol, propylene glycol or glycerol have preservative action.
·        High concentration of syrup has high osmotic pressure thus acts as preservative.
·        Chloroform Water, Chloroform Spirit have preservative action.
·        Benzoic acid, methyl parahydroxybenzoate acid (methyl paraben) or propyl parahydroxynenzoate (propyl paraben) may be used as additional preservatives.

Example: Preparation of Piperazine Citrate Elixir IP
Formula:              Piperazine citrate                             180g
                              Chloroform Spirit                             5ml
                              Glycerin                                             100ml
                              Orange Oil                          0.25ml
                              Syrup                                   500ml
                              Purified water up to          1000ml
Method: Piperazine citrate is dissolved in small amount of purified water. Orange oil, glycerin, syrup and chloroform spirit is mixed. Sufficient volume is added to produce the final volume.
Use: Anthelmintic.

GLYCERIN
Definition: These are solutions or medicaments in glycerol with or without water.
e.g. Thymol Glycerin B.P.C.
e.g. Borax Glycerin IP
Formula:              Borax                   120g
                              Glycerin                              880g
Method: Borax is triturated with glycerol in a mortar. Then the mixture is warmed with constant stirring to make a clear solution. Filtered if required.
Use: Bacteriostatic.
e.g. Phenol Glycerin IP
Formula:              Phenol                  160g
                              Glycerin                              840g
Method: Phenol and glycerin are mixed in a beaker. The beaker is warmed gently until is becomes a solution.
Use: Local anaesthetic and local antiseptic. Phenol glycerin is used to prepare Phenol Gargle and Phenol Glycerin Ear Drop.
Cautions: Phenol Glycerin when diluted with water becomes caustic so it is diluted with glycerin.
Label: FOR EXTERNAL USE ONLY should be displayed in the label.

LINCTUSES
Definition: Linctuses are viscous, liquid, oral preparations that are usually prescribed for the relief of cough.
Use: Linctuses are used for treatmentof cough.
Active ingredients: They contains sedatives and expectorants.
Vehicle:
Syrup IP (67%w/w or 85%w/v sucrose solution) – has sweet taste, has preservative action, viscous.
Glycerol – has demulcent action, sweet in taste.
Sorbitol – Used in preparations for diabetic patients, viscous.
Invert Sugar – Sweet and viscous.

[N.B. Demulcents are inert substances that soothe inflammed mucous membrane or skin by preventing contact with air/irritants in the surroundings.]


Adjuncts:            
Chemical stabilizers – Invert sugar has reducing action. This reduces the oxidative degradation of various colors and flavors. Hence color and flavors of fruit juices are better preserved in invert syrup.
Coloring agents: Coal tar dyes       e.g. Amaranth – red color.
                                                            e.g. Compound Tartrazine Solution – yellow color.
Flavoring agents:               e.g. Tolu Syrup
                                             e.g. Fruit flavors like lemon and blackcurrant
                                             e.g. Oxymel – has acidic, honey-like sweet taste.
                                             e.g. Benzaldehyde Spirit – has almond-like flavor.
Preservatives:     Syrup (67%w/w) has high osmotic pressure hence acts as self-preservative.
                              Chloroform Spirit
                              Benzoic acid solution
Examples of Linctuses:
(i) Codeine Linctus, paediatric B.P.C.         (ii) Codeine Linctus, Diabetic
(iii) Diamorphine Linctus                                             (iv) Compound Tolu Linctus, Paediatric

Codeine Linctus, Paediatric B.P.C.
Formula
Codeine Phosphate
Lemon Syrup
Benzoic acid solution
Chloroform Spirit
Purified Water
Compound Tartrazine Solution
Syrup, up to
3g
200ml
20ml
20ml
20ml
10ml
1000ml
Active ingredient (cough suppressant)
Flavor
Preservative
Preservative
Solvent for codeine phosphate
Color
Vehicle (viscous and sweet)
Method of preparation:
(i)     Codeine phosphate is weighed and taken in a conical flask.
(ii)   Water is added to the flask, heated gently to dissolve.
(iii) Color, benzoic acid solution and chloroform spirit are added one at a time and mixed thoroughly after each addition.
(iv)  Lemon syrup is added and mixed. Syrup is added and mixed.
Container: Codeine phosphate degrades in light so an amber color bottle is used.
Label:    “To be sipped and swallowed slowly without adding water.”

[N.B. As linctuses are intended to soothe the throat they should not be diluted or swallowed quickly. To get prolonged contact with the mucous membrane it must be sipped slowly.]

MILKS AND MAGMAS
Milks and Magmas are aqueous suspensions of insoluble, inorganic drugs. Their particles are bigger than the particles of gel. When prepared they are viscous and because of this there is no need to add a suspending agent.
Examples:            Bentonite Magma USP,
Dihydroxyaluminium Aminoacetate Magma USP
Milk of Magnesia USP , Magnesium Hydroxide Mixture BP (Cream of Magnesia)
Milk of Bismuth USP
Method of Preparations: There are two methods of preparations
(a) Hydration method       and (c) Hydration and Precipitation method.
(a) Hydration method:
Light magnesium oxide (MgO) is hydrated with water to produce magnesium hydroxide [Mg (OH)2].
MgO    +   H2O   ®   Mg(OH)2.
This method is followed by industries and in Milk of Magnesia USP.
Disadvantage:
This method produces highly viscous preparation that is difficult to pour out.
The pH of the preparation is 10. This produces an alkaline taste that is unpleasant. So 0.1% citric acid is added to reduce the alkalininty and improve the taste.
Advantage: Industrially this method is used because this method does not require washing.

(b) Hydration and Precipitation method:
(i)     A solution of sodium hydroxide (NaOH) is triturated with light magnesium oxide to form a smooth cream. It is diluted with water.


(ii)   The cream is mixed with a magnesium sulfate (MgSO4) solution while stirring.
MgSO4   +  2NaOH    =   Mg(OH)2¯   +   Na2CO3.
MgO  +  H2O  = Mg(OH)2¯
(iii) After some time the magnesium hydroxide will settle. The supernatant liquid is decanted and the precipitation is washed with purified water. Again the supernatant liquid is decanted. This process is continued until the preparation is free from sulfate. [How will you test that the preparation is sulfate free?]
(iv)  The precipitation is mixed with chloroform water to give the final preparation.

Advantages:        (i) The product is neither very viscous nor sediment quickly.
                              (ii) Produce a salty taste that is more pleasant than the product obtained from hydration method alone.


MUCILAGES
Definition: Mucilages are thick, viscous, adhesive liquids produced by dispersing gum in water, or by extracting mucilaginous substances from plants with water.
Examples:
Name of the mucilage
Preservative used
Source
Indian Gum Mucilage IP
Chloroform water
Acacia arabica
Acacia Mucilage NF
Benzoic acid
Acacia senegal
Tragacanth Mucilage BPC
Alcohol and Chloroform Water
Astragalus gummifer
Starch Mucilage B.P.C.
No preservative
Starch from maize or wheat
Use:
·        Mucilages are used as suspending agents in suspension preparations to reduce the rate of sedimentation.
·        Acacia mucilage is used as suspending and emulsifying agents in different preparations taken orally. It is very sticky hence never used in external preparations.
·        Tragacanth mucilage is more viscous than Acacia mucilage, hence the former is used to suspend heavy indiffusible powders or resinous tinctures. It is less sticky than Acacia mucilage so can be used in external preparations lke jellies, lotion, pastes and creams.
·        It is used with other mucilages for its high viscosity.

Preparation of Acacia mucilage
Formula:              Acacia, tears (or powder)               40g
                              Chloroform Water             60ml
Chloroform Water, 60ml is taken in a beaker. Acacia powder (or acacia tears) is taken in a muslin cloth and tied as a bag. The bag is suspended in the beaker without touching the bottom of the beaker. It is left for 2 to 3 days until the solution is complete. The final product is gently stirred.
Preparation of Tragacanth mucilage
Formula:              Tragacanth                         12.5g     – gum
                              Alcohol(90%)                    25ml      – dispersing agent
                              Chloroform Water             1000ml  – vehicle with preservative action
Alcohol (90%) 20ml is taken in a wide mouthed bottle. Tragacanth powder is added to it and dispersed. Chloroform water is added quickly, bottle is closed and shaken vigorously to produce the solution. Volume is made up with the chloroform water.
Preparation of Starch Mucilage
Formula:              Starch                   25g
                              Purified Water to               1000ml
Water 200ml is boiled in a conical flask.
In a mortar starch is triturated with 30ml of cold water.
The suspension is then poured in the boiling water and shaken. Rest of the water is added and mixed and boiled until a gelatinized.
Immediately cooled (so that no skin is formed) by rotating the conical flask under running tap water.
Water is added to make up the volume up to 1000ml.

N.B. Other synthetic mucilages are made from methyl cellulose, sodium carboxymethylcellulose, polyvinyl alcohol etc.

Disadvantages:
·        Acacia mucilage becomes acidic by enzymatic degradation. Acacia contains an oxidase enzyme that oxidize easily oxidizable drugs.
·        Tragacanth mucilage thickens on storage.
COLLODIONS
Definition:
Collodions are liquid preparations for external use. They are applied with a brush. The vehicle is volatile and evaporates on application to the skin, leaving a flexible, protective film covering the site.
·        The volatile solvents are ether and alcohol.
·        The film-producing ingredient is pyroxylin (nitrocellulose).
·        The substance giving the flexibility is called plasticizer. Here castor oil acts as plasticizer.
Classification of collodions
(i)     Unmedicated Collodion e.g. Flexible Collodion IP. This is useful for protecting small cuts and abrasions.
(ii)   Medicated Collodion e.g. Salicylic acid collodion BPC contains 12%w/v salicylic acid in flexible collodion. These are provided for prolonged contact between the skin and medicament (drug).

Flexible Collodion IP
               Pyroxylin             16g
               Colophony          30g
               Castor oil             20g
Alcohol (90%)    240ml
Solvent Ether q.s.              1000ml
Method of preparation:
(i)     Pyroxylin is immersed in the alcohol (90%v/v) in a bottle.
(ii)   Colophony and the Castor oil are added.
(iii) Suffcient solvent ether is added.
(iv)  The bottle is closed and shaken and allowed to stand for a few days, while impurities settle and then the supernatant solution is decanted.
N.B.
Pyroxylin is a nitrated cellulose obtained by treating defatted cotton with a mixture of nitric and sulfuric acid. Its principal constituent is cellulose tetranitrate.
It is highly inflammable, so it is kept moist with methylated spirit and stored loosely packed, in a well-closed container, protected from light and in a cool place. Before use it is allowed to dry in air.
Collophony / Rosin: It is pale-yellow or brownish yellow glass-like solid residue left after distilling volatile oil from the oleoresin obtained from species of pinus. It is used for its adhesive quality.

Storage
·        Air tight container is used to reduce the evaporation of organic solvents.
·        Smaller bottles (5ml) are used because from larger bottle the loss of solvent is higher whenever the cap is removed.
·        The cap is fitted with a brush, or glass rod or a plastic applicator.
·        The bottle should be amber colored and fluted.

N.B. Fluted bottles are used for external preparations.

Label:
               ‘For external use only’
               ‘Store in a cool place’
               ‘Highly inflammable, keep away from naked flame.’
 


Questions for Test-I
Q1. What do you mean by:             [2]
               (i) Aromatic waters           (ii) Spirits            (iii) Elixirs           (iv) Glycerin       (v) Linctus
               (vi) Milks & Magmas       (vii) Mucilages   (viii) Collodions
Ans. Give the definition, main features and uses of each dosage form. Do not give the preparation, storage or instructions.
Q2. Describe the method of preparation of :                            [3]
               (i) Camphor Water IP                                                    (ii) Concentrated Peppermint Water IP
               (iii) Chloroform Spirit IP                                              (iv) Piperazine Citrate Elixir IP
               (v) Borax Glycerin IP                                                    (vi) Codeine Phosphate Linctus Paediatric IP
               (vii) Milk of Magnesia                                                  (viii) Flexible Collodion
Q3. Give examples of pharmacopoeial preparations of
(i) Aromatic waters           (ii) Spirits            (iii) Elixirs           (iv) Glycerin       (v) Linctus

               (vi) Milks & Magmas       (vii) Mucilages   (viii) Collodions – Ans. Give only the names not formulas.