Pharmaceutical Solutions. Definition: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents.

1. Md. Saiful Islam
BPharm, MPharm (PCP)
North South University
Fb Group: Pharmacy Universe
Solutions 2

2. Solvents for pharmaceutical use
- Solubility is a property which is determined by the chemical
nature and structure of both solute and solvent
- In the selection of a proper solvent fro a given solute, the
structural similarity as well as toxicity, volatility and stability
are taken under consideration
- Sometimes, a mixture of solvents is desirable to dissolve
certain compounds
- The agents usually used as solvents in the preparation of
solutions are water, alcohol, glycerin, propylene glycol, corn
oil, isopropyl alcohol etc

3. Water
- The most widely used solvent in pharmaceutical
dispensing and manufacturing
- It is a good solvent for most inorganic salts and for many
organic compounds
- Its miscibility with other solvents like alcohol, glycerin
makes it a useful vehicle for many pharmaceutical
preparations

4. Purified water
- Ordinary drinking water from tap is not acceptable for the
manufacture of most aqueous pharmaceutical preparations
because of possible incompatibilities between dissolved solids
and the medicinal agents which is visible by precipitation,
discoloration or effervescence
- Purified water, USP obtained by distillation, ion exchange
treatment, reverse osmosis or other suitable process has only
1% as much dissolved solid as tap water
- Purified water, USP is intended for use in preparation of aqueous
dosage form except those intended for parenteral administration
- Water For Injection, USP; Bacteriostatic Water For Injection,
USP or Sterile Water For Injection, USP is used for injection

5. Methods for purified water preparation
Distillation method:
- Distillation is probably the oldest method of water
purification
- Water is first heated to boiling
- Then the water vapour rises to a condenser where
cooling water lowers its temperature. The vapour is
condensed, collected and stored
- Organics with boiling points lower than water can’t be
removed efficiently and can actually become
concentrated in the product water

6. A = dirty water
B = heat to boiling point
C = water vapour
D = condenser
E = purified water
Figure: Water distillation process

7. Distillation…
- Generally the first portion of aqueous distillate (about
first 10-20%) must be discarded, since it may contain
many foreign volatile substances
- Also the last portion of water (about 10% of the original
volume of water) remaining in the distillation apparatus
must be discarded and not subjected to further
distillation because distillation to dryness undoubtedly
result in decomposition of remaining solid impurities to
volatile substances that would contaminate the
previously collected portion of distillate

8. Ion Exchange method
- The ion exchange equipment generally passes water
through a column of cation and anion exchangers
consisting of water insoluble synthetic polymerized
phenolic, carboxilic,amino or sulfonated resins of high
molecular weight
- These resins are mainly of two types:
i) The cation or acid exchanger which exchange a
hydrogen ion for any cation in the solution (Na+, Ca+2,Al+3)
ii) The anion or base exchanger which exchange a
hydroxyl ion for any anion (Cl-)

9. Figure: Mechanism of ion exchange

10. Ion Exchange method…….
- The hydrogen ion from cation exchanger units
with the hydroxyl ion from the anion exchanger
to form pure water
- Water purified in this manner is referred to as
demineralized or deionized water
- This system efficiently removes ions but not
effectively remove most organics and
microorganisms

11. Reverse osmosis
- Reverse osmosis is the most economical methods of removing 90%
to 99% of all contaminants
- This process removes virtually all viruses, bacteria, pyrogens and
organic molecules and 90-99% ions
- In this process, a pressurized stream of water is passed to the inner
side of a filter membrane core
- A portion of feed water, permeates the membrane as filtrate, while
the rest of the water sweeps along the membrane to exit the system
without being filtered called concentrate because it contains the
contaminants rejected by the membrane

12. Figure: Reverse osmosis process

13. Reverse osmosis…..
- In natural osmosis, the flow through a membrane (semi permeable)
is from less concentrated solution to more concentrated solution
driven by osmotic pressure
- But in reverse osmosis system, hydraulic pressure is applied to the
concentrated solution and flow is from more concentrated solution to
the less concentrated solution counteracting the osmotic pressure.
So, it is called reverse osmosis.
- Because reverse osmosis membranes are very restrictive, they yield
slow flow rates. Storage tanks are required to produce an adequate
volume in a reasonable amount of time

14. Reverse osmosis…..
- Depending on the pore size, reverse osmosis membranes can
remove particles defined in the range of-
micro filtration (0.1-2 μg; bacteria)
ultra filtration (0.01-0.1 μg; virus)
nano filtration (0.001-0.01 μg; organic compounds
in the molecular range of 300-1000)
and particles smaller than 0.001 μg

15. Alcohol (ethyl alcohol, ethanol) USP
- Next to water, alcohol is the most useful solvent in Pharmacy
- It is used as primary solvent for many organic compounds
- Together with water, it forms hydro alcoholic mixture that dissolves
both water soluble and alcohol soluble substances, especially used
in the extraction of active constituents from crude drugs
- Alcohol, USP is 94.9-96%(v/v) at 15.56°C. Dehydrated alcohol, USP
contains not less than 99.5%(v/v)
- Alcohol is often preferred due to its miscibility with water and its
ability to dissolve many water insoluble ingredients including drug
substances, flavourants and antimicrobial preservatives

16. Alcohol……..
- Alcohol is frequently mixed with glycerols & glycerin to reduce
the amount of alcohol required
- It has some undesired pharmacologic and potential toxic
effects when ingested in pharmaceutical product, particularly
by children
- FDA has proposed restriction on the use of alcohol in drug
products like –
For children under 6 years, alcohol limit is 0.5%
For children of 6-12 years, alcohol limit is 5%
For children over 12 years, alcohol limit is 10%

17. Dilute Alcohol, NF :
- It is prepared by mixing equal volumes of alcohol, USP and purified
water
- It is a useful hydro alcoholic solvent in various pharmaceutical
process and preparations
Alcohol, Rubbing:
- Rubbing alcohol contains about 70% of ethyl alcohol by volume.The
remainder consists of water, denaturants with or without color
additives, perfume oils and stabilizers
- Each 100ml must contain 355mg of sucrose octa-acetate or 1.4 mg
of denatonium benzoate, bitter substances that discourages
accidental or abusive oral ingestion and also discourages illegal
removal of the alcoholic content of rubbing alcohol (as denaturants
are impossible to separate by distillation)

18. Alcohol, Rubbing……
- It is employed as rubefacient externally and as a soothing rub for
bed ridden patients, a germicide for instruments, a skin cleanser
prior to injection
- It is also used as a vehicle for topical preparations
Glycerin,USP (Glycerol) :
- Glycerin is a clear syrupy liquid with a sweet taste
- It is miscible with both water and alcohol
- As a solvent it is comparable with alcohol
- It has preservative qualities, often used as stabilizer
- Used as auxiliary solvent in conjugation with water or alcohol in
many internal preparations

19. Isopropyl rubbing alcohol:
- It is 70% isopropyl alcohol by volume. The remainder consists of
water with or without color additives, stabilizers and perfume oils
- It is used externally as rubefacient and soothing rub and as a vehicle
for topical products
- Commercially available as 91% isopropyl alcohol solution and used
for preparing needles & syringes and for disinfecting the skin by
diabetic patients
Propylene glycol, USP:
- A viscous liquid, miscible with water and alcohol
- It has a wide range of application as useful solvent and frequently
substituted for glycerin in modern pharmaceutical formulations

20. Preparation of solutions
- Most solutions are prepared by simple mixing of solutes with
the solvent
- The usual method for preparing solutions at the preparation
counter requires the use of a mortar and pestle. The solute,
which has been reduced previously to a fine powder by
trituration in a mortar, is dissolved by pouring solvent on it
and triturating it until solution takes place
- In some instances, it may be desirable to dissolve the solute
in a flask or bottle or by heating the solute and solvent in a
suitable vessel

21. Preparation…..
- Solution of substances, like pepsin & protein, may be
prepared most efficiently by placing the solute on the
surface of the solvent contained in a beaker or
evaporating dish and allowing solution to take place by
circulatory diffusion
- On an industrial scale, solutions are prepared in large
mixing vessels with ports of mechanical stirrers. When
heat is desired, thermostatically controlled mixing tanks
may be used

22. Pharmaceutical ingredients used in preparations
for oral solution
- Most drug substances in use today are unpalatable and unattractive
in their natural state. For that reason, they are prepared as colorful,
flavorful formulations making attractive to the sight, smell and taste
to the patient.
- The proper combination of flavor ,fragrance and color in a
pharmaceutical product contributes to its acceptance.
- In the preparation of solutions, one or more solvents are used to
dissolve the drug substance. The other ingredients used are –
1) Acidifying agent:
- Used to provide acidic medium for product stability
- Examples: Citric acid, Acetic acid, Fumaric acid, HCl, HNO3

23. 2) Alkylating agent:
- Used to provide alkaline medium for product stability
- Examples: ammonium solution, Ammonium carbonate, Monoethanol
amine, Diethanolamine, KOH, NaOH, Na borate, NaHCO3, Na2CO3,
Trolamine
3) Antifungal preservative:
- Sometimes dilute vegetable extract and flavoring agents provide
favorable media for the growth of bacteria & fungi. Antifungal
preservatives are used to prevent growth of fungi.
- Examples: Methyl paraben, Ethyl paraben, Propyl paraben, Butyl
paraben, Benzoic acid, Sodium benzoate, Sodium propionate.
** Effectiveness of parabens is usually enhanced by use in
combination

24. 4) Antimicrobial preservative:
- Used to prevent growth of microorganisms
- Examples: Benzalkonium chloride, Benzethonium chloride, Benzyl
alcohol, Cetyl pyridinium chloride, Chlorobutanol, Phenol, Phenyl
ethyl alcohol, Phenyl mercuric nitrate, Thimarosal.
5) Antioxidant:
- Used to prevent deterioration of preparations by oxidation
- Examples: Ascorbic acid, Ascorbyl palmitate, Butylated
hydroxytoluene, Hypo phosphorus acid, Monothioglycerol, Propyl
gallate, Sodium ascorbate, Sodium bisulfite, Sodium formaldehyde,
Sulfoxylate, Sodium metabisulfite.

25. 6) Buffering agent:
- Used to resist change in pH upon dilution or addition of acid or alkali
- Example: Potassium metaphosphate, Potassium phosphate
(monobasic), Sodium acetate, Sodium citrate (anhydrous &
dihydrate)
7) Chelating agent:
- Forms stable water soluble complexes (chelates) with metals
- Examples: Edetic acid, Disodium edetate
8) Colorant:
- Used to impart color to liquid preparations
- Example: FD & C Red No.3; FD & C Blue No.2; D & C Orange No.5;
Caramel; Ferric oxide; Red.

26. 9) Clarifying agent:
- Used as a filtering aid fir its adsorbent quality
- Example: Bentonite
10) Flavoring agent:
- Used to impart a pleasant flavor and often odor to a preparation
- Examples: anise oil, Cinnamon oil, Cocoa, Menthol, Orange oil,
Peppermint oil, Vanillin.
11) Sweetening agent:
- Used to impart sweetness to a preparation
- Examples: Aspartame, Dextrose, glycerin, Mannitol, saccharin
sodium, Sorbitol, Sucrose.

27. 12) Flavored sweetened:
- Examples: Acacia syrup, Aromatic syrup, Aromatic elixir, Cherry
syrup, Cocoa syrup, Orange syrup, Syrup.
13) Solvent:
- Used to dissolve all the ingredients in preparation of a solution.
- May be aqueous or not
- Co-solvents such as water & alcohol, water & glycerin may be used
when needed
- Sterile solvents are used in certain preparations
- Examples: Alcohol, Corn oil, Cotton seed oil, Glycerin, Isopropyl
alcohol, Mineral oil, Oleic acid, Peanut oil, Purified water, Water for
injection, Sterile water for injection, Sterile water for irrigation.

28. Other different types of solutions
Dry mixtures for solution:
- A number of medicinal agents, particularly certain antibiotics, have
insufficient stability in aqueous solution to meet extended shelf life.
So, they are provided in dry powder or granule form for
reconstitution with a prescribed amount of purified water
immediately before dispensing to the patient
- The dry powder mixture contains all of the formulative components,
including drugs, flavorants, colorants, buffers and others, except for
the solvent.

29. - After reconstitution, the solution remains stable when stored in the
refrigerator for the labeled period, usually 7-14 days, depending on
the preparation
Examples:
- Cloxacillin Sodium for oral solution, USP (an anti-infective antibiotic)
- Penicillin V Potassium for oral solution, USP (anti-infective)
- Potassium Chloride for oral solution, USP (a potassium supplement)

30. Oral Rehydration Solutions
- Oral rehydration solutions are usually effective in treatment of
patients with mild volume depletion, 5-10% of body weight
- A liter of typical oral rehydration solution contains:
45 mEq of Na+
20 mEq of K+
35 mEq of Cl-
30 mEq of citrate
25 gm of dextrose

31. Syrups
- Syrups are concentrated aqueous preparations of a sugar or sugar
substitute with or without flavoring agents and medicinal substances
- Syrups provide a pleasant means of administering a liquid form of a
disagreeable tasting drug
- Syrups contain little or no alcohol
Components of syrup:
Most syrups contain the following components in addition to the
purified water and any medicinal agents present:
a) The sugar, usually sucrose or sugar substitute used to provide
sweetness and viscosity
b) Antimicrobial preservatives
c) Flavorants and
d) Colorants
Also many syrups, especially those prepared commercially, contain
special solvents, solubilizing agents, thickeners or stabilizers

32. Classification of syrups
A) Depending on the presence of medicinal agent:
1) Medicated syrup:
- Medicated syrups are employed in therapeutics for the value of
the medicinal agent present in the syrup
- These are commercially prepared by combining each of the
individual components of the syrup, such as sucrose, purified
water, flavoring agents, coloring agents, the therapeutic agent and
other necessary & desirable ingredients
- Perhaps the most frequently found types of medications
administered as medicated syrups are antitussive agents and
antihistamines

33. 2) Non-medicated syrups:
- Syrups containing flavoring agents but not medicinal substances
are called non-medicated syrups or flavored vehicles
- Examples are: cherry syrup, Orange syrup, Cocoa syrup,
Raspberry syrup etc.
B) Depending on the presence of sucrose:
1) Sugar based syrup:
- Those which are concentrated solution of a sugar
- Sucrose is one of the purest of commercially available substances
and is the preferred carbohydrate for syrup
- Most syrups contain a high proportion of sucrose, usually 60-80%,
not only for desirable sweetness and viscosity but also for
inherent stability

34. Sugar based syrup…….
- Concentrated sugar solutions are resistant to microbial growth due
to unavailability of water required to microbial growth
- Generally , preservatives are not used in it, if used soon. But if it
needs to store, preservatives are added
- If syrup were completely saturated with sucrose, in cool storage,
some sucrose might cryatallize from solution and allows the
separation of more sucrose that is disproportionate to its solubility.
The syrup then becomes unsaturated & probably suitable for
microbial growth
- Some official syrups and commercial syrups are not made as
saturated syrup. So, preservatives are added to ensure their stability
during their period of use and storage

35. 2) Non-medicated syrups:
- Those which are formulated with artificial sweetening agents and
viscosity builders
- Non-medicated syrups are designed to satisfy the need of persons
who must exclude sugar from their diet
- Here, the glycogenetic substances are replaced by non-glycogenetic
substances like methyl cellulose or hydroxy ethyl cellulose
- These cellulose derivatives impart viscosity like sucrose syrup
- The addition of one or more artificial sweeteners gives them
appearance of a true syrup