Bule Hora University

College of Health and Medical Sciences

Department Of Pharmacy
Integrated Physical Pharmacy and Pharmaceutics I

By: Aliyi Gerina [B.pharm]

Chapter 6
Pharmaceutical Solutions

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 Out Line

• Introduction

• Formulation of solutions (API and Excipients)

• General methods of preparation

• Solutions taken orally

• Solutions used in the mouth and throat

• Solutions instilled into body cavities

• Topical solutions

• Injectables (sterile products)

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Introduction

Liquid Dosage
Forms

Monophasic
Liquid DFs Poly-phasic
(Solutions) Liquid DFs

Aqueous Non-aqueous
solutions Suspensions Emulsions Colloids
solutions

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 Introduction…

o Solution: solutions are clear Liquid preparations containing one or more

active ingredients dissolved in a suitable vehicle.

o Colloids: A system in which finely divided particles, which are 1 nm - 0.5

µm in size, are dispersed within a continuous medium in a manner that
prevents them from being settled rapidly.

o Suspension: (Solid in Liquid dispersion) Liquid preparations containing one

or more active ingredients suspended in a suitable vehicle.

o Emulsion (Liquid in Liquid dispersion): Emulsions are two phase system in

which one liquid is dispersed through out another liquid in the form of small
droplets.

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 Introduction…

 Solution:
 Is a homogeneous mixture composed of two or more substances

 One substance (solute) is dissolved in another substance (solvent).

 The solute is the component present in the smallest amount

 The solvent is the larger liquid component.

 The solute is dispersed throughout the solvent in molecular or ionic sized particles.

 It is a thermodynamically stable, one-phase system.

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Introduction…

 Steps in making a Solution

1) Breaking up the solute into individual components:

=>expanding the solute

1) Overcoming intermolecular forces in the solvent to make room for the

solute:

=>expanding the solvent

1) Allowing the solvent and solute to interact

=> form the solution

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 Advantages and Disadvantages

 Advantages  Dis Advantages

 Ease of administration  They are less stable than solid DFs.
 Faster absorption.  Unpleasant flavours can be difficult
 Uniform dosage. to mask.

 Provide safe means of  They are bulky to transport.

administering certain substances  A spoon is needed to administer the
 like potassium iodide and bromide dose.
that cause gastric pain if taken dry.  Accidental breakage to the container
 Have attractive appearance- results in complete and messy loss of

 psychological effect. the contents..

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Classification of Solutions

 Based on route of administration

Pharma
Solutions

Used in the mouth Instilled into Applied to body

Taken orally and throat body cavities surfaces

 Syrups  Mouth Washes  Douches  Collodions

 Elixirs  Gargles  Enemas  Liniments
 Spirits  Throat Paints  Ear Drops  Lotions
 Linctuses  Throat Sprays  Nasal Drops  Paints
 Nasal Sprays

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Classification of Solutions…

 Based on vehicle used

Pharma
Solutions

Aqueous Sweet or Non-aqueous

solutions Viscid solutions

 Douches  Syrups  Elixirs

 Enemas  Spirits
 Gargles  Collodions
 Mouth washes  Glycerins
 Nasal Washes  Lotions
 Sprays  Liniments
 Otic Solutions
 Inhalations

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 Pharmaceutical Applications

 Solutions have a wide variety of  They are also used as:

uses in the pharmaceutical industry.
 Flavorings
 They are used therapeutically as
vehicles for:  Buffers
 Oral  Preservatives and
 Parenteral  Suspending agents for a
 Topical variety of liquid dosage forms
 Otic
 Ophthalmic
 Nasal products

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Solvents for solution preparation

 Solvent selection is based on:

 Solubility
 Clarity
 Toxicity
 Viscosity
 Compatibility with excipients
 Chemical inertness
 Palatability
 Odor
 Color and
 Economy.

 In most cases,
 water is the preferred solvent.
 It meets the majority of the above criteria.

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 Solvents for solution preparation…

Water:
 The major ingredient in most of liquid dosage forms is water.
 It is used both as a vehicle and as a solvent.

Advantages:
o Tastelessness,
o freedom from irritating qualities and

o lack of pharmacological activity make it ideal for such purposes.

Disadvantages:
• Favorable medium for some chemical reactions, and
• Supports the growth of microorganisms when contaminated.

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Solvents for solution preparation…
 The USP recognizes six types of water for the preparation of dosage
forms.

1) Purified water

2) Water for injection

3) Sterile water for injection

4) Bacteriostatic water for injection

5) Sterile water for inhalation

6) Sterile water for irrigation

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 Solvents for solution preparation…
 Purified water:
• The preferred and most commonly used vehicle in the solutions.
 The source or feed water for the production of purified water is
drinking water.
 It must meet the requirements for ionic and organic chemical purity
 It must be protected from microbial contamination.
 It should be protected from recontamination and microbial
proliferation.
 It is used in as an excipient in the
 production of non-parenteral and non ophthalmic products.
 It is also used for
 cleaning of certain equipment’s and non-parenteral product-contact
components.
 Commonly produced by:
 Ion Exchange
 Reverse Osmosis (RO) and
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 Distillation Bule Hora University
Solvents for solution preparation…

a. Distillation
o Separation method based on boiling point
difference.
o Generally, the first portion of aqueous
distillate (10% to 20%) must be discarded

o the last portion of water (10% of the original

volume of water) remaining in the distillation
apparatus must be discarded.

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Solvents for solution preparation…

b. Ion Exchange Method

o The ion exchange equipment generally passes water through a column of cation
and anion exchangers
o consisting of water insoluble synthetic polymerized phenolic, carboxylic, amino, or sulfonated
resins of high molecular weight.

o These resins are mainly two types:

 the cations, or acid exchangers

 the anions, or base exchangers

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 Solvents for solution preparation…

c. Reverse Osmosis
o Cross-flow (or tangential flow) membrane filtration

o a pressurized stream of water is passed parallel to the

inner side of a filter membrane core.

o A portion of the feed water permeates the membrane as

filtrate.

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Solvents for solution preparation…

oDepending on their pore size, cross-flow filter membranes can remove

particles defined in the range of
 microfiltration (0.1 to 2 μm, e.g., bacteria);

 Ultrafiltration (0.01 to 0.1 μm, e.g., virus);

 nanofiltration (0.001 to 0.01 μm, e.g., organic CPDs in the mwt range of
300 to 1,000); and

 particles < 0.001 μm

oReverse osmosis removes virtually

o all viruses, bacteria, pyrogens, and

o organic molecules and 90% to 99% of ions

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 Solvents for solution preparation…
 Water for injection (WFI):
 Conforms to the standards of purified water,
 but is also free of pyrogen.

 It contains no added substances

 May not be sterile

 It is used as a
 solvent for the preparation of parenteral solution

 Collected in sterile & pyrogen free container (glass or glass lined)

 Clear, colourless, odourless and having a pH of 5 -7.

 Must be used within 24 hour

 For products to be sterilized after preparation.

 Must store in tight container at suitable temperature

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Solvents for solution preparation…
 Sterile Water for injection:
 It is water for injection that
 is sterilized and
 packaged in single-dose containers of type I and II glass.

 Packed in container of 1 Liter or less

 It is designed solely
 for parenteral use only.

 It contains no antimicrobial agents or other preservatives.

 Due to sterilization may contain slightly more solid content.

 Intended to be used as a solvent, vehicle or diluent for already

sterilized & packed injectable.
 Non-pyrogenic.
 Must be added aseptically

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 Solvents for solution preparation…
 Bacteriostatic water for injection:
 It is sterile water for injection containing one or more suitable bacteriostatic
agents.

 Sterile

 Non-pyrogenic

 0.9% (9 mg/mL) of benzyl alcohol added as a bacteriostatic preservative.

 Filled in vials/syringe in volume not more than 30ml

 Intended for small volume injectable (multi-dose vials)

 Not to be used with large volume parenteral (usually with 5ml or less).

 Repeated withdrawals may be made to dilute or dissolve drugs for injection.

 The pH is 4.5 to 7.0

 It is parenteral preparation

 Indicated only for diluting or dissolving drugs

 for intravenous, intramuscular or subcutaneous injection.
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Solvents for solution preparation…
 Sterile water for inhalation:
 Is water for injection that is
 packaged and rendered sterile
 It is intended for use in inhalators
 It carries a less stringent specification for bacterial endotoxins than
SWFI
 It contains no antimicrobial agents.
 Should not be used for parenteral administration.
 Sterile water for irrigation:
 It is water for injection packaged and
 sterilized in single-dose containers
 It may be larger than 1 L and allow rapid delivery of their contents
 It is not required to meet particulate matter in injections
 It contains no antimicrobial agents or other added substance.

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 Solvents for solution preparation…

 Alcohol:
 Glycerin: Mainly used as:
 The second most commonly used
 Solvent, Sweetening agent,
solvent (for many organic compounds).
Antimicrobial preservative and
 A hydro-alcoholic mixture is capable of Viscosity increasing agent.
dissolving both  Propylene glycol:
 alcohol soluble and water soluble  Solvent, Extractant, and
substance.
Preservative in a variety of liquid
 Alcohol is often preferred because of: pharmaceutical formulations, including
 is widely used for its miscibility with water parenterals
 ability to dissolve many water insoluble
 Can also be used as antiseptics.
ingredients.

also possess an antimicrobial

preservative activity.

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 Formulation and manufacturing considerations

 Formulation Manufacturing
considerations: Consideration:
1) Solubility 1) Raw Materials
2) Stability
2) Equipments
3) Preservatives
4) Pharmaceutical elegance 3) Manufacturing Procedure
 Viscosity modifiers
 Sweetening agents
 Flavoring agents
 Coloring agents

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 Formulation considerations
 Solubility:
 Approaches to increase the solubility of the drug:
o pH adjustment: A large number of drugs are either weak acids or weak bases. The solubility of
these agents can be markedly influenced by the pH of the environment

o Co-solvency: Weak electrolytes and non polar molecules frequently have poor water solubility.
These types of solutes are more soluble in a mixture of solvents than in one solvent alone. This
phenomenon is known as co-solvency.

o Micelle solubilization: At high concentration surfactants are forced into water to form colloidal
aggregate known as micelle. Drugs get adsorbed into micelle that increase drug solubility.

o Complexation: Solubility of a compound may be increased by complexing with a complexing

agent. e.g. solubility of para amino benzoic acid (PABA) may be increased by complexing with
caffeine.

o Micronization: The process involve size reduction of drug particle 1 to 10microns either by spray
drying or fluid energy mill

o Chemical modification of the drug: Poorly soluble drugs are chemically modified into water soluble
derivatives
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 Formulation considerations…

 Stability: B. Physical Stability

A. Chemical stability:  A stable formulation retains its
Affected by viscosity, color, clarity, taste,
1) pH
and odor throughout its shelf life.
2) Temperature
3) Ionic Strength
4) Solvent effects
5) Light Objective Subjective
6) Oxygen evaluation evaluation
Instability can be prevented by:
1) Use of buffering agents  Color: spectrophotometr  Taste and odor can
be determined either
2) Use of antioxidants  Clarity- turbidity or light
by pharmaceutical
scattering equipment.
3) Proper packaging (e.g.: use of amber  Viscosity- viscometers. investigator or by a
bottle for light sensitive products) panel of unbiased,
taste sensitive
individuals.

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Formulation considerations…

 Preservatives:
 Preservatives must have following criteria:

1) Effective against broad spectrum of microorganisms.

2) Physically, chemically and microbiologically stable for lifetime of the product.

3) Non toxic, non sensitizing, soluble, compatible and

4) With acceptable taste and odor.

 Types of Preservatives
1) Acidic : phenol, benzoic acid, sorbic acid

2) Neutral preservatives : chlorobutanol, benzyl alcohol

3) Quaternary ammonium compounds: Benzalkonium chloride

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Formulation considerations…

 Pharmaceutical Elegance:
 Viscosity modifiers: Enhance viscosity. E.g.: Povidone, hydroxyethylcellulose
 Sweetening agents: To enhance palatability and mask the taste of the drugs.
Eg : Sucrose, saccharin, aspartame
 Flavoring agents: To mask unpleasant taste
Taste Sensation Recommended flavor
Salt Butter scotch, maple, apricot, peach, vanilla,
Bitter Wild cherry, walnut, chocolate, mint
Sweet Fruit and berry, vanilla
Sour Citrus flavours, liquorice, raspberry

 Coloring agents: To enhance the appearance of the vehicle;

 which matches well with the flavor employed in the preparation .
E.g.: green with mint, brown with chocolate flavor etc.

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Manufacturing considerations
 Raw Materials :
 Incoming raw materials should be tested as per specifications that is identity,
purity, uniformity and microbial contamination.

 Equipments :
 The following types of equipments may be used in

manufacture of liquid formulations:-

1) Mixing tanks (SS 316 Stainless Steel) equipped with an agitator.
2) Measuring devices for large and small amount of solids and liquids.
3) A filtration system e.g. filter press

 Cleaning of equipments:-
 All equipments must be thoroughly cleaned and sanitized before use.
 Disinfectants used: Dilute solutions of H2O2, phenol derivatives.
 Sterilized by: Alcohol, boiling water, autoclaving, steam or dry heat.

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Manufacturing considerations…

 Manufacturing Process:
Process Flow Control Measured
Variables Response

Addition of Raw Materials

(Active +Excipients as per formula)

Mixing  Mixing time

(Jacketed vessel with variable speed mixer)  Clarity
 RPM  Viscosity
 Temp  Assay
 Final volume
Filtration
(Filter Press or cartridge filter)  Pore size
 Clarity
 Filter integrity

Filling  Filling machine

 Volume
(Automatic Filling Machine) speed

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 Preparation of Solutions…

 Methods for preparation of solutions:

1) Simple solutions:
Prepared by dissolving the solute in most of the solvent,
 mixing until dissolved, then adding sufficient solvent to bring the solution up to the
proper volume(by stirring or heating).
2) Solution by chemical reaction:
 Are prepared by reacting two or more solutes with each other in suitable
solvent.
3) Solution by extraction:
 Drugs often are extracted with water or with water containing other
substances.

 Preparations of this type more often classified as extracts.

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 Solutions taken orally
Oral solution absorption from GIT into the systemic circulation
may be expected to occur more rapidly than suspension or solid dosage
forms of the same medicinal agent.
 Liquid oral solutions are aqueous formulations.
 To be acceptable for patients,
these must be palatable.
Flavouring, colouring and sweetening agents are therefore added
 to enhance their appearance and taste.
 The dose is usually in multiples of 5 mL, and
the patient is given a 5 mL spoon with the solution.
When smaller volumes are required, oral syringes are used.
 Solution pH is usually 7.0, although a range of pH 2–9 can be tolerated.
 In formulating or compounding a pharmaceutical solution,
the pharmacist must use information on the solubility and stability of
each solute with regard to the solvent or solvent system.
 For many medicinal agents, their solubility in the usual solvents are stated in
the United States Pharmacopeia– National Formulary (USP–NF)
as well as in other reference books.

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 Aromatic Water
o Aromatic waters are clear, aqueous solutions saturated with volatile oils or
other aromatic or volatile substances.

o They are used principally as flavored vehicles.

o Their odors and tastes are similar to those of the drugs or volatile substances
from which they are prepared.

o Aromatic waters were prepared from a number of volatile substances

o Includes

o chloroform water,

o Camphor water,

o peppermint water and

o anise water

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 Aromatic Water,…

 Chloroform water

 Diluted chloroform water is prepared by mixing 1part of double

strength chloroform water (official formulae) and 1part of water.

 Use: preservative, flavor

Camphor water

o Diluted camphor water is prepared by mixing 1part of concentrated

camphor water (official formulae) and 40 parts of water.

o Use: flavor, mild expectorant

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 Aromatic Water,…

o Aromatic water will deteriorate with time therefore:

- should be made in small quantities

- protected from intense light and excessive heat by storing in air tight, light
resistant containers.

o If they become cloudy or otherwise deteriorate;

o they should be discarded.

o Deterioration may be
o due to volatilization, decomposition or microorganism growth.

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 Aromatic Water,…
● There are two official methods of preparation of aromatic waters
(a) Distillation process

(b) Solution process

(a) Distillation process:

e.g. Stronger Rose Water NF

● The aroma containing substance should be coarsely ground and mixed with
sufficient quantity of purified water in the distillation unit.

● After distillation any excess oil in the distillate is removed by filtration.

(b) Solution process

e.g. Peppermint water

● Aromatic water may be prepared by shaking volatile substance with purified water.

● The mixture is set a side for 12 hours & filtered.

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 Syrups
 Definition: Syrups are concentrated, viscous, aqueous solutions of 85% sugar or
a sugar substitute with or without flavors and medical substances.

 Classification based on their use:

1) Medicated syrup– When the aqueous preparation contains some added medicinal
substance
2) Non‐medicated/Flavored syrup– contained various aromatic and pleasantly
flavored substances and
is intended as a vehicle or flavor for preparations.

 Classification based on their basic formula:

1) Sugar Based syrups– sucrose and dextrose are usually employed in the
preparation of syrups
2) Artificial sweeteners– sugar‐free syrups which are intended as substitute for
sugar‐based syrups and
o are intended to be administered to persons who must regulate their sugar/calorie intake

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 Syrups…

 Advantages:
 Dis advantages:
 Appropriate for any patient,
 Delayed onset of action as
whatever the age is
absorption takes time
 The most natural and easiest
 Not suitable in emergency and for
route of administration
unconscious patients
 Economical and safe to the patient
 Not convenient for patients with GI
 No nursing is required (the patient
disorder such as diarrheas,
can take it without help)
constipation, ulceration and hyperacidity
 Liquid DF is expected for certain types in stomach
of products like cough medicines
 Can’t avoid first pass metabolism

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Syrups…

 Components of syrup:
 Medicinal agent  Miscellaneous
 Special solvents,
 Purified water
 Solubilizing agents,
 Antimicrobial preservatives  Thickeners or
 Stabilizers
 Sweetening agent

 Viscosity modifiers

 Flavorants

 Colorants

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Syrups…
Components of syrup….

 Antimicrobial Preservatives

 The amount varies with the proportions of water available.

 Among the preservatives, the most commonly used are:

1)Benzoic acid‐0.1% to 0.2%
2)Sodium benzoate –0.1 to 0.2%
3)Combination of methyl, propyl, butyl parabens totaling 0.1%

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Syrups…

 Sugar and other sweeteners:

 Sugar and dextrose are mostly used

 The difficulty or problem with dextrose are as follows:

1) Forms saturated solutions at 70%w/v (less viscous)

2) Dextrose dissolves more slowly

3) Dextrose is less sweet

4) Saturated solution supports growth of microorganism

 Saccharin sodium is 300 ‐550 time as sweet as sucrose.

 It may be used in concentration of 0.1 to 0.2%

 Characterized by a bitter after taste.

 Sorbitol can also be used as sweetener

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 Syrups…

 Flavorants for syrup:

 Are used to render the syrup pleasant tasting.

 Most syrups are flavored with synthetic or naturally occurring flavorants

 E.g. volatile oil, vanillin, and others,

 The flavorants used must possess sufficient water solubility

 Colorants:

 To enhance appeal of the syrup,

 The colorant should correlate with the flavorant employed.

 The colorant used is generally

 Water‐soluble,

 Non‐reactive with other components, and

 Stable
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Syrups…

 Preparation of Syrups:
 Pharmaceutical syrups are produced by mixing purified water,
sweeteners, active ingredients (API), aromas, flavors and other
ingredients (thickeners) etc.

Solid Ingredients
Dosing systems Production Tanks

Liquid Ingredients

Filling Machine Storage Tanks Filtration

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Syrups…

 Preparation of Syrups:
 Syrups are generally prepared using one of the following four
techniques depending upon the physical and chemical
characteristics of the ingredients.
1) Solution with the aid of heat

2) Agitation without heat (simple admixture of liquid components)

3) Addition of sucrose to a prepared medicated liquid or a flavored liquid

4) Percolation method

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 Syrups…

 Solution with Heat:

 This is a suitable preparation method if the constituents are
 not volatile, degraded by heat, or when it is desirable to make the syrup rapidly.

 Procedure:

 Purified water is heated to 80–85 0C

 After removing from its heat source, sucrose is added with vigorous agitation

 Heat-stable components are added to the hot syrup

 The mixture is allowed to cool

 Heat labile and volatile components (e.g. alcohol and oil) are added after cooling to
room temp.

 Volume is adjusted to by the addition of purified water.

 Caution: Do not apply excessive heat -inversion of sucrose causing discoloration

 Examples: Acacia syrup, NF; Cocoa Syrup, NF; Syrup USP (85% sugar, made by cold and hot
process, percolation)

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 Syrups…

 Agitation without Heat.

 To avoid heat-induced inversion of sucrose

 This method is used for

 heat sensitive and

 volatile substances.

 Procedure:

1) Take a vessel of greater capacity than the volume of syrup to be prepared

2) Place sucrose and other formulation ingredients in the vessel

3) Dissolve in purified water allowing intense agitation without spillage.

 Examples: Ferrous Sulfate Syrup, Ephedrine Sulfate, Citric acid Syrup, and
Glycyrrhiza Syrup

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Syrups…

 Addition of sucrose to a liquid medication:

 Often used with fluid extracts (tinctures)

 Syrup made in this way usually develops precipitates

 Many such tinctures and fluid-extract contain alcohol-soluble

constituents and are prepared with alcoholic vehicles

o Alcohol is often an ingredient of the liquids, and

o the resinous and oily substances solubilized by the alcohol

precipitate when water is added.

 Examples: Senna Syrup, NF and Cherry Syrup

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Syrups…

 Percolation Method:
 The principle of percolation is used.

 Either purified water or the source of the medicinal component is passed slowly
through a bed of crystalline sucrose, thus dissolving it and forming syrup.

 Procedure:

1) Purified water or aqueous solution of a medicating or flavoring liquid is

allowed to pass slowly through a column of crystalline sucrose to
dissolve it.

2) The percolate is collected and returned to the percolator as required until

all of the sucrose has been dissolved.

 The sucrose bed should be coarse.

 Shape of the percolator must be cylindrical or cone shaped.

 Example: Tolu Balsam syrup -flavor for cough syrup

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Syrups…

 Packaging of syrup:  Storage of Syrups:

 The general process  Generally, syrups are stored at

 Filling room temperature in tightly

closed bottle.
 Sealing

 Capping

 Coding and labeling

 Wrapping

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Elixirs
 Elixirs are clear, pleasantly flavored, sweetened hydro-alcoholic liquids.
 They are intended for oral use.
 Because of their hydro-alcoholic character,
 elixirs are better to maintain both
 water soluble and alcohol soluble components in the solutions than the aqueous syrups.
 More preferred than syrups due to the stability character.
 Elixirs are less sweet and viscous than syrups
 They contain a lower portion of sugar
 Less effective in masking the taste of medicinal substances

 Advantage of elixirs

• Ease of dosage administration to patients who have difficulty swallowing solid

forms.

 A disadvantage of elixirs

• For children and for adults who choose to avoid alcohol is their alcoholic content.

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Elixirs…

 Classification of Elixirs:

 Based on the concentration of alcohol:

 Based on their use:

1) High alcoholic elixirs: o Flavored elixirs:

75-78 % alcohol o are non medicated and

1) Low alcoholic elixirs: o used as flavors and vehicles

8-10% alcohol  E.g. Aromatic elixir, Isoalcoholic

elixir, Benzaldehyde elixir
NB.: Elixirs containing at least 10-12%
alcohol o Medicated elixirs:

• are already “self-preserving”. o contain potent medicament

 E.g. Diphenhydramine HCl elixir,
Phenobarbital elixir, Theophylline
Elixir.

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 Elixirs…

Components of Elixirs
1. Vehicles:
2. Adjuvants:
o Alcohol and water are primary solvents o Used to improve safety, efficacy and
 Alcohol content may vary from 5-40 % palatability
 Chemical stabilizers: Citric acid
o If the concentration of alcohol is high, and disodium editate in Neomycin
Elixir
o aqueous soluble substances may
 Preservatives: 20% alcohol, syrup
precipitate, or
and methyl paraben and propyl
o If the concentration of water is high, paraben
 Coloring agents: Coal tar dyes
o alcohol soluble substances may
 Sweetening agents: sucrose,
precipitate sorbitol, glycerin, saccharin
o Sorbitol, glycerin and propylene glycol are  Flavoring agents: Black current
adjuncts. syrup, raspberry syrup, lemon syrup
and orange syrup etc
3. Medicinal substances:
o An elixir may contain water and alcohol
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soluble substances.
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 Elixirs…
 Preparation of elixirs:
 Elixirs are usually prepared:
1) Simple solution method with agitation
2) Add mixture of two or more solutions
 Alcohol soluble and water soluble components

 are generally dissolved separately in alcohol and purified water, respectively.

 Then the aqueous solution is added to alcoholic solution rather than the reverse,
 in order to maintain the highest possible alcoholic strength at all times so that
minimal separation of alcohol- soluble components occurs.
 When the two solutions are completely mixed the mixture
 is made to volume with specified solvent or vehicle.

 Storage:
o Elixirs should be stored in tight, light resistant containers and

o protected from excessive heat because of their usual content of volatile oil and alcohol.
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Linctuses:
Definition: Linctuses are viscous, monophasic liquid preparation containing a high
concentration of syrup intended to sipped and swallowed slowly for treatment of
cough.

 Use:  Dosage:
 Demulcent,  The usual dose is 5ml and part of
 Sedative and the doses must be diluted to this
 expectorant action. volume.

 Administration:  Dilutions must be freshly prepared

To obtain and prolong local action, and
linctuses should be taken undiluted  not more than two weeks supply should
and sipped and swallowed slowly. be issued at a time, unless other wise
specified

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 Linctuses…

 Formulation:
 Vehicles:
 The diluent is syrup (Tolu syrup)
 In codeine linctuse is chloroform water is used.
 Adjuvants:
 Chemical stabilizers: Mostly stable because of syrup
 Preservatives:
 High concentration of syrup acting as preservative,
 Benzoic acid is used in codeine linctuses.
 Coloring agents: Coal tar dyes
 Flavoring agents:
 Black current syrup,
 lemon syrup,
 benzaldehyde etc.

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Spirits:
 Alcoholic or hydro-alcoholic solutions of volatile substances.
 Spirits could be classified according to their uses:
• Therapeutic spirits:
 Contain therapeutic volatile substances.
 May be taken orally, applied externally, or used by inhalation.
 When taken orally, they are generally mixed with a portion of water
 to reduce the pungency of the spirit.
 E.g. Aromatic spirit of ammonia
• Flavoring spirits :
 Contain flavoring volatile substances.
 E.g. Compound orange spirit, compound cardamom spirit.

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 Spirits…
 Volatile substances in the spirits is more than that of aromatic water.
 Spirits could also contain greater concentration of aromatic substances than the corresponding aromatic
waters.

 Generally, the alcohol concentration of spirits is rather high (usually over 60%).
 Because of the greater solubility of aromatic or volatile substances in alcohol than in water.

 Amount of alcohol differ from one spirit to another

 The lowest amount of alcohol found in internal spirits as (aromatic spirit of ammonia)

 Contain 62-68% alcohol

 While (camphor spirit) which is used externally

 contain 80-87%.

 When mixed with water or with an aqueous preparation,

 the volatile substances separate from solution and

 form a milky preparation.

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 Spirits…

 Preparation of Spirits:

1) Simple Solution

 Majority of spirits are prepared by dissolving the solute in alcohol by

agitation.

 Filtration is generally desirable to obtain a sparking clear product.

 Example: Aromatic Spirit

2) Solution with Maceration

 Macerate the vegetable materials in a suitable substance.

 Example: Peppermint Spirit (maceration of peppermint leaves)

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Spirits…

3) Solution by Chemical Reaction

 Preparation of Aromatic Spirit of Ammonia NF,

 Preparation of Ethyl Nitrate Spirit
4) Distillation

 No spirits currently official are prepared by distillation,

 However, two products of historical significance which is official in
NF are prepared by distillation.
 Examples:
 Brandy (48-54% alcohol, distilled from red grapes) and
 whisky (47-53% alcohol, distilled from hops, barley and other grains)

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Spirits….
 Route of administration of spirits:

 Taken orally: Brandy and whisky

 Used by inhalation: Aromatic sprit of ammonia

 Applied externally.

 Uses of official spirits :

 Carminative (aromatic spirit of ammonia)

 Antacid (aromatic acid of ammonia)

 Mild reflex circulatory stimulant (camphor spirit)

 Flavoring agent (cinnamon spirit)

 Storage:
 Spirits should be stored in tight, light resistant containers and in a cool place.

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 Solutions used in the mouth and throat
Gargles
Gargles are aqueous solutions frequently containing
antiseptics, antibiotics and/or anesthetics
used for treating the throat by forcing air from the lungs
through the gargle,
which is held in the throat; subsequently, the gargle is
expectorated.
• Many gargles must be diluted with warm water prior to use.
• The product should be labeled so that it cannot be mistaken
for preparations intended for internal administration.
“not to be swallowed in large amounts”.

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 Mouthwashes

Mouthwashes can be used for therapeutic & cosmetic purposes

● Therapeutic mouthwashes can be formulated
to reduce plaque, gingivitis, dental carries.
● Cosmetic mouthwashes may be formulated
to reduce bad breath

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Mouthwashes …
Mouthwashes generally contain 4 groups of excipients

1. Alcohols:
o It enhances the flavor, provides sharpness to the taste,
o aids in masking the unpleasant taste of active ingredients.

o functions as
o a solubilizing agent for some flavoring agents, and

o may a preservative.

2. Humectants: such as glycerin and sorbitol

o increase the viscosity of the preparation

o enhance the sweetness of the product

o improve the preservative qualities of the product

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 Mouthwashes,…

3. Surfactants

 Non ionic and anionic surfactants

 aid in the solubilization of flavors.

 Cationic surfactants such as cetylpyridinium chloride

 are used for their antimicrobial properties, but these tend to impart a bitter taste.

4. Flavours

 are used to overcome disagreeable tastes.

 e.gs of principal flavoring agents are peppermint, cinnamon, menthol...

5. Colouring agents

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Topical solutions
Liniments:
 Definition:
 Alcoholic or oleaginous solutions or emulsions of various medicinal substances
intended for external application to the skin,

 generally with rubbing.

 Liniments are liquid preparations intended for external application.

 Types:
1. Alcoholic liniment-
 used as rubefacient ( induce mild irritation with reddening of the skin), counterirritant,
mildly astringent and penetrating effect.

2. Oily liniments- are milder in action and less irritating to the skin than the alcoholic,
 used as protective coating and
 use as rubefacient for muscular pain
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Liniments…
 Two types of vehicle are used for liniments that are solutions.

 High concentration of alcohol (as in Soap Liniment)

 Oil (as in Camphor Liniment).

 Although alcohol is primarily used as a solvent,

 it aids penetration of medicaments into the skin and

 It is also potentiates their counter-irritant or rubefacient action.

 Liniments should never be applied to broken skin because

 they would be very irritating, especially if the solvent is alcohol.

 Cool storage is necessary because all Liniments have volatile ingredients.

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Liniments…

 Different Forms by which Liniments  All liniments Must Bear A Label

can occur:- Indicating
1) As a emulsion
1) For external use only
2) As a suspension
3) As a solution 2) Shake well for emulsion or suspension

3) Store in tight containers

 Methods of Preparation
4) Not to be applied to bruises or broken
o Liniments are prepared in the same
skin areas
manner as

o solutions,

o emulsions or

o suspensions.

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Lotions:

 Are liquid or semi liquid preparations

 meant for external application to the skin.
 The medium employed can be aqueous or alcoholic or suspensions in
aqueous medium.
 About half of the official lotions are solutions.
 Application: While
 liniments are stimulating preparations
are applied vigorously,
 lotions are usually smoothing and
are applied gently by dabbing.
 Uses:
cooling,
smoothing or
protective action to the skin.

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Lotions…

 Formulation:
 Medicaments

 Vehicles: Purified water, alcohol and Isopropyl alcohol

 Co-solvents: Glycerin, propylene glycol, poly ethylene glycol

 Flavoring agents: Rose water

 Preservatives: Methyl paraben, propyl paraben

 If lotions are alcoholic or hydro-alcoholic preservatives are not required

 If lotions are aqueous preservatives are incorporated

 Categories of medicaments used in lotions:

1) Antiseptics (zinc oxide, precipitated sulphur)

2) Astringents (calamine, zinc oxide, zinc sulphate, precipitated Sulphur)

3) Germicides.
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 Lotions…

 Method of preparation  Label

 Simple solution method  For external use only
 Storage:  Shake well before use
 Lotions should be stored in a cool
 Sore in cool place
place, away from flame or heat
 because of the presence of highly  Direction: Apply without
 volatile and inflammable solvents like alcohol rubbing or friction.
(95%) or industrial methylated spirit.

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Paints
 All the official paints are solutions.

 Water is the solvent for Crystal Violet Paint,

 But organic solvents, alone or mixed with water, are used for other paints.

 Dyes are often light, fine powders that easily float into the air if carelessly handled.

 Can be applied onto

 skin and

 mucous membranes.

 All paints cannot be used for application onto mucous membrane

 All paints, except throat paints are labeled 'For external use only'.

 Skin paints:

contain volatile solvent that evaporates quickly

to leave a dry resinous film of medicament.

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Paints…

 Throat paints:

 Are viscous due to a high content of glycerol,

 Designed to prolong contact of the medicament with the affected site.

 Glycerine is commonly used as a vehicle.

 Are applied to the affected part with the help of cotton plug,

 They should be applied as such, without dilution with water.

 Medicaments used:
 Astrigents: Tannic acid, Boric acid

 Antiseptics: Iodine, Crystal violet

 Anti-infectives: Phenol

 Analgesics: Clove oil, Potassium Permanganate

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Paints…

 Throat paints….

 Components:  Label:
 Medicaments  FOR EXTERNAL USE ONLY
 Glycerin  STORE IN A COOL PLACE
 Sweetening agents
 SHAKE WELL BEFORE USE
 Flavoring agents
 NOT TOBE SWALLOWED
 Stabilizers
 KEEP THE CONTAINER TIGHTLY CLOSED
 Preservatives
 Storage:
 Method of preparation:
 In a cool and dark place.
 Simple solution.

 Examples:
 Crystal violet paint
 Compound iodine throat paint

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 Collodions
 Are liquid preparations containing pyroxylin (soluble gun
cotton, collodion cotton),
 dissolved in a solvent mixture usually composed of ethyl ether and
ethanol with or without medicinal substance.

 When the ether and ethanol have evaporated,

 leave a film of pyroxylin on the surface.

 Intended for external use only.

 Applied to the skin

 by means of a soft brush or other suitable applicator.

 Uses Of Collodion

1) As a protective coating to the skin.

2) As medication where a thin layer of the medication is

firmly placed against the skin.

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Collodions….
Can be medicated or non medicated
Salicylic Acid Collodion
Flexible collodion
Official medicated collodion
a non-medicated collodion and
10% solution of salicylic acid in
flexible collodion. used as a vehicle for medicated
collodions.
It is used for its keratolytic effects,
is prepared by adding
especially in the removal of corns
 2% camphor and 3% castor oil to
from the toes. collodion.
The castor oil renders the
product flexible,
 permitting its comfortable use
over skin areas that are normally
moved, such as joints, fingers,
and toes.
The camphor makes the product
waterproof.

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Collodions….

 Storage:

Stored in small light-resistant, well closed containers at a

temperature not exceeding 20 0C.
 Label:

 ‘For external use only’

 ‘Store in a cool place’

 ‘Highly Inflammable’

 ‘Keep away from naked flames’

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 Solutions instilled into body
cavities
Enemas
 Enemas are also known as Clyster

 Are preparations intended for introducing in the rectum for

 cleansing, therapeutic or diagnostic purposes.

 Given at body temperature

 Injected slowly with enema syringe.

 Types Of Enema:

1) Evacuation Enemas- employed to promote evacuation.

2) Retention Enemas- For local action in the rectum

a) Nutritive Enema - supply nutrient to the patient

b) Medicated Enema - supply medication for systemic effect

3)Diagnostic Enema - BaSO4 enema

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Douches
 A douche is an aqueous solutions which is directed into body cavity.
 It functions as
 a cleansing or antiseptic

 Usually directed using Bulb syringe.

 Types of douches
• Eye douches
• are used to remove foreign particles and discharges from the eyes.
• is directed gently at an oblique angle and
• is allowed to run from the inner to the outer corner of the eye.
• Pharyngeal douches
• are used to prepare the interior of the throat for an operation and
• to cleanse it in supportive conditions.
• Similarly, there are
• nasal and vaginal douches.
• Douches most frequently dispensed in the form of a powder
• Directions for dissolving in a specified quantity of water.
 Example: Dobell’s Solution Tablets (Compound Sodium Borate Solution NF)

 Used as nasal or pharyngeal douches.

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Douches…
 Among the components of douche powders are the following:

 Boric acid or sodium borate

 Astringents, e.g. potassium, ammonium, zinc sulfate

 Antimicrobials, e.g. oxyquinoline sulfate, povidone iodine

 Quaternary ammonium compounds, e.g. benzethonium chloride

 Detergents e.g., sodium lauryl sulfate

 Oxidizing agents, e.g., sodium perborate

 Salts, e.g., sodium citrate, sodium chloride

 Aromatics, e.g. menthol, thymol, eucalyptol, methyl salicylate, phenol

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 Nasal Solutions
o solutions are usually aqueous nasal solutions
o designed to be administered to the nasal passages in drops or sprays.

o Nasal drops spread more extensively than the spray.

o Three drops cover most of the walls of the nasal cavity, with the patient in a supine position
and head tilted back and turned left and right

o The adult nasal cavity has about a 20 mL capacity with a large surface area (about 180 cm2)
for drug absorption afforded.

o Another advantage nasal deliverly is to avoids first-pass metabolism by the liver.

o The nasal tissue is highly vascularized making it an attractive site for rapid and efficient
systemic absorption.

 For some peptides and small molecular compounds, intranasal bioavailability has been

comparable to that of injections.

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Nasal Solutions…
o Commercial nasal preparations
o include antibiotics, antihistamines and drugs for asthma prophylaxis.

o Nasal solutions are prepared are similar in many respects to nasal secretions,
o so that normal ciliary action is maintained.

o Aqueous nasal solutions usually are isotonic and

o slightly buffered to maintain a pH of 5.5 to 6.5.

o Nasal sprays are solutions of drugs in aqueous vehicles &

o are applied to the mucous membrane of the nose by means of an atomizer
or nebulizer.

o The spray device should produce relatively coarse droplets

o if the action of the drug is to be restricted to the upper respiratory tract.

 Fine droplets tend to penetrate further into the respiratory tract than is desirable.

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 Otic Solutions
o Otic solutions occasionally are referred to as ear or aural preparations.

o Ear preparations are usually placed in the ear canal by drops for

o the removal of excessive cerumen (ear wax) or

o the treatment of ear infections, inflammation, or pain.

o The main classes of drugs used for topical administration to the ear include

 local anesthetics, e.g. benzocaine

 antibiotics e.g. neomycin

 anti-inflammatory, e.g hydrocortisone

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 Otic Solutions…
o These preparations include the main types of solvents used
o glycerin, propylene glycol or water.

o The viscous glycerin or PG vehicle

o permits the drug to remain in the ear for a long time

o Viscous liquids like glycerin or propylene glycol either

o are used alone or in combination with a surfactant

o to aid in the removal of ear wax

o For aqueous preparations to act,

o it is necessary for the patient to remain on his side for a few minutes so the drops
do not run out of the ear.

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Parenteral Solutions

 “Parenteral” comes from two Greek words,

 “Para”(outside)

 “Enteron” (intestine)

 Meaning “Beside the intestine”.

 Injected directly in to body

 It by passes alimentary canal

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Parenteral solutions…

 Advantages:
 Disadvantages:
 Fastest method of delivering  Traumatic injury from the insertion
drugs (quick onset of action) of needle; pain at site
 Provides higher concentration  Potential for introducing toxic
of drug to bloodstream or tissues agents, microbes and pyrogens

 Vomiting and unconscious  Impossible to retrieve if adverse

reactions occurs
patients can take
 Correct syringe, needle, and
 Can provide fluids, electrolytes technique should be used
and nutrients
 Trained personnel required
 Drug action can be prolonged
 Necessity of aseptic condition in
by modifying the formulation production, compounding and
 Drugs with poor absorption or administration
instability in GIT  Expensive

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Parenteral solutions…

 Routes of administration:
 Intravenous (IV) Vein
 Intramuscular (IM) Muscle
 Subcutaneous (SC) Under the skin
 Intradermal (ID) Into the skin

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 Parenteral solutions

Necessities for parenteral preparations:

 Sterility  Do not use coloring agents

 Pyrogen-free  Prepared under aseptic
 Free from particulate matter conditions

 Clarity  Special clothing (gowns, masks,

 Stability hair net, gloves).

 Laminar flow hoods placed in
 Chemical purity
special rooms
 Iso-tonicity
 Special and high quality
 Solvents and vehicles used
packaging
must meet special purity and
other standards.

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Parenteral solutions

 Classification based on volume:

Parenteral Products
(based on volume)

Small Volume Large Volume

Parenterals Parenterals

 Pharmaceutical products  Electrolytes

 Biological products  Carbohydrates
 Radiopharmaceutical products  Nutritional Solutions
 Liposomes and lipid products  Proteins
 Lipid Emulsions
 Peritoneal Dialysis
 Irrigating Solutions
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Parenteral solutions

 Classification….

Parameter SVP LVP

Volume 100 and less 101-1000 ml

Routes IV, IM, SC IV-LVP, Non IV-LVP

Dosage unit Single or multiple dose Single dose

Technique Vein puncture Venoclysis

Preservative Used Not used

Buffer Used Not used

Formulation Solution, suspension, emulsion Solution and O/W emulsion

Isotonicity Not essential Must

Example furosemide injection Dextrose 40%,NS,DNS and
Oxytocin injection
RL

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 Parenteral solutions…
 Classification based on formulation:

Parenteral Formulations
(Dosage Forms)

Solutions Emulsions Suspensions

 Injectable
emulsion

Aqueous Oil-based Aqueous Oil-based

Ready to Powders for Ready to use Powders for

use reconstitution reconstitution
 Injection  For injection  Injectable
 For injectable
suspension
suspension
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 Injection: are liquid preparations that are substances or solutions, E.g.
Insulin injection

 For injection solution: dry solids that upon addition of suitable vehicles
yield solutions, E.g. Cefuroxime for injection, USP

 Injectable emulsion: liquid preparation of drug substance dissolved or

dispersed in a suitable emulsion medium, E.g. Propofol, USP

 Injectable suspension: liquid preparation of solid suspended in a

suitable liquid medium. E.g. Methyl Prednisolone Acetate Suspension, USP

 For injectable suspension: dry solid that upon addition of a suitable

vehicle yields injectable suspensions. E.g. Imipenem/Cilastatin Injectable
Suspension, USP

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Parenteral solutions

Formulation of parenteral solutions:

 Active drug

 Solvents (co-solvents) and Vehicles

 Adjuvants

 Surfactants

 Polymers

 Preservatives

 Buffers

 Tonicity adjusters

 Antioxidants

 Chelating agents

 Inert gases

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 Vehicles:
 Solvents & vehicles must meet special purity & other standard to assure
sterility, stability and safety.

 Vehicle used should be:

 Pharmacologically inert,

 Non toxic and compatible with blood,

 Maintain solubility of the drug,

 Be physically and chemically stable

 Does not affect the pH.

 Must be pyrogen free.

 No particulate mater.

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Aqueous vehicles:
Water for injection, USP:
o is intended for use
o in the preparation of parenteral solutions and
o in the preparation of some bulk pharmaceutical chemicals (in the large-scale
manufacturer of injections).

o It must be protected from microbial contamination.

Sterile water for injection, USP

o It is prepared from water for injection that is sterilized and suitably packaged

o It is packaged in single-dose containers not larger than 1L

o It contains no antimicrobial agent or other added substance.

o It is used as diluents for parenteral products

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Bacteriostatic water for injection, USP:

o is sterile water for injection

o which contain one or more suitable antimicrobial agents.

o It is intended to be used as diluent for parenteral products.

o It is packaged in single or multiple-dose containers (vials), not larger

than 30 mL size
Sodium chloride injection, USP
o Is a sterile isotonic solution of sodium chloride in water for injection
o May be used as a sterile vehicle in solutions or suspensions of drugs for
parentral administration
o Contain no antimicrobial agents.

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Bacteriostatic Sodium chloride injection, USP

o Is a sterile isotonic solution of sodium chloride in water for injection.

o Contains one or more suitable antimicrobial agents.

Ringer’s injection, USP

o Is a sterile solution containing NaCl, KCl, and CaCl2 in water for injection.

o The three agents are present in concentrations similar to those of

physiological fluids.

o Used as a vehicle and as an electrolyte replenisher and plasma volume

expander.

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Non-aqueous vehicles

o Are sometimes used when there are limited water solubility of drugs or
susceptibility to hydrolysis.

o Fixed vegetable oils like corn oil, cottonseed oil, peanut oil, and sesame oil

o But not mineral oil or paraffin b/c not absorbed by body tissues.

o Alcohol;PEG, glycerol, propyl glycol,

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 Surfactants:
 Enhance drug solubility

 May be incorporated to aqueous or oil-based vehicles

 Examples: Non ionic surfactants (tweens, poloxamers)

 Polymers:

 Hydrophilic polymers to enhance drug solubility by complexation

 Example: Polyvinyl alcohol

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 Preservatives:
 As a bacteriostatic
 To inhibit any microbes accidentally introduced while doses are being withdrawn.
 A must in multiple dose containers unless the drug itself is bacteriostatic
 As adjuncts in aseptic filling and in intermittent heat sterilization
 Not permitted in single doses > 15 ml
 Not for routes reaching cerebrospinal fluid or inter-ocular.
 Not for oil-based parenteral products (due to the low water activity of this medium)
 Examples:
 Benzyl alcohol (0.9% to 1.5%)
 Methylparaben (0.18% to 0.2%)
 Propylparaben (0.02%)
 Benzalkonium chloride (0.01% to 0.02%)- in ophthalmic dosage forms
 Thiomersal (0.001% to 0.01%)
 Phenolic compounds: Phenol (0.25-0.5% w/v), Chlorocresol (0.1-0.3% w/v)
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 Buffers:
 Parenteral preparations should not vary significantly form physiological pH (about 7.4)

 Acidic or alkaline solutions may be needed to

 solubilize or

 stabilize drugs.

pH Buffer system Concentration

3.5-5.7 Acetic acid-acetate 1.0-2.0

2.5-6.0 Citric acid-citrate 1.0-5.0

6.0-8.2 Phosphoric acid-phosphate 0.8-2.0

8.2-10.2 Glutamic acid-glutamate 1-2

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 Tonicity adjusters:

 Can be:
 Electrolytes: NaCl

 Non-electrolytes: Glucose, mannitol, Glycerine

 An isotonic solution is one that exhibits the same effective osmotic

pressure as blood serum.
 Example of isotonic: Dextrose injection 5% and NaCl injection 0.9%

 Hypotonic Solution: is a solution of lower osmotic pressure than that of

a body fluid.

 Adjusted to isotonicity using Sodium chloride, Glucose, Mannitol

 Hypertonic solutions: the solutions having a higher osmotic pressure

than that of a body fluid.

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 Antioxidants:
 Oxidative degradation of drug in solution is mediated either
 by molecular oxygen or
 by free redicals and
 can be catalyzed by metals, heat, light and hydrogen ions.

 Oil soluble:
 Water soluble
 Propyl gallate
 Sulfurous acid salts
 Butylated hydroxyanisole
 Ascorbic acid isomers
 Ascorbyl palmitate
 Thiol derivatives
 α-Tocopherol

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 Chelating agents:  Inert Gas

 Boiling the water
 Sequester heavy metals
 Displacing the air in the solution
 to prevent the catalysis of oxidation with nitrogen.
reaction.  Purging container N2 or CO2 before
filling.
 Examples:
 Topping off container with the gas
 Ethylenediamine tetra acetic acid after sealing
 Use glass-sealed ampoules
 Citric acid and

 tartaric acid

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 Manufacturing Steps in Parenteral Solutions:

Heat sensitive APIs Heat stable APIs

Cleaning of containers, Cleaning of containers,
closures and equipments closures and equipments

Collection of materials Collection of materials

Preparation of parenteral products

Preparation of parenteral products
Filtration
Aseptic filtration
Filling
Aseptic filling
Sealing
Aseptic sealing Sterility,
Pyrogen, Sterilization
Evaluation Clarity,
Leak test,
Assay
Evaluation
Labelling and Packaging
Labelling and Packaging
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 Parenteral packaging systems:

 Injectable formulations are packaged into containers made of glass or plastic.

 Container systems include ampoules, vials, syringes, cartridges, bottles, and

bags:

 Ampoules are all glass, whereas bags are all plastic.

 The other containers can be composed of glass or plastic and

 must include rubber materials, such as

 rubber stoppers for vials and bottles and

 rubber plungers and rubber seals for syringes and cartridges.

 Irrigation solutions
 are packaged in glass bottles with aluminum screw caps.

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 Glass:  Plastic:
 Is employed as the container material of choice
 Plastic containers can also be
for most Small Volume Parenterals (SVP).
used
 The USP provides a classification of glass:

1) Type I, a borosilicate glass;  But they face the following

2) Type II, a soda-lime treated glass; problems:
3) Type III, a soda-lime glass; and  Permeation
4) Non-parenteral glass: a soda-lime glass
 Sorption
not suitable for containers for parenterals.
 Leaching

 Softening

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 Ampoules:  Vials:
 Sealed glass containers  Drugs are packaged in vials either as
 With an elongated neck that must liquids or powders
be broken off  Made of glass or plastic
 Most are weakened around the  Are sealed with a rubber stopper
neck for easy breaking  A needle is needed to add contents to
 Sealed after filling single dose of or withdraw from vials
drug /water.  May be designed for single or multi-
 Most commonly used dose use
 for supplying WFI.  Multi-dose vials contain a preservative
 They are also used  to inhibit bacterial contamination
 for single dose SVPs.  Product is easier to remove from vials
 A 5 micron filter needle should be than form ampoules
used when drawing the contents

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 Comparison:
Ampoules Vials

Single dose Single / multi dose

No Preservatives Preservative

Hermetically sealed (air tight) Not hermetic

Protection from air or humidity Air /humidity may permeate

Drugs more stable Drugs less stable

Difficult opening Easy opening

Risk of injury No risk of injury

Risk of glass contamination No risk of contamination

Container is not reusable Vials are reusable

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 Closures:  Problems associated with rubber

 To provide closure for closures are:

 multiple dose vials,  Incompatibility

 IV fluid bottles,  Chemical instability

 plugs for disposable syringes and  Physical instability

 Characteristics of good pharma
 bulbs for ophthalmic pipettes,
rubbers:
 rubber Closure is material of choice.
 Good ageing qualities
 Satisfactory hardness and elasticity
 Resistance to sterilization conditions
 Impermeable to moisture and air

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 Pre-filled syringes:
 Single-dose medicine filled in syringe with fixed needle.

 Plastics / glass sometime

 Labeled properly.

 Emergency drugs are available right away.

 Ease of administration (less steps involved) .

 Self administration is possible.

 Reduction of medication error (right dose always)

 Reduction of contamination (Assurance of sterility).

 Less overfill required (economical for biopharmaceuticals)

 Good control of controlled drugs (e.g. narcotics).

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 Glass/Plastic Bottles & Plastic Bags:

 They are used for Large volume parenterals

 For IV administration.

 For the intermittent or continuous infusion of fluids

or drugs.

 Need special administration devices to permit drug

administration.

Cannula Saline Set

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 Labelling:
 Name and concentration of active substances

 Name and concentration of any added antimicrobial preservatives

 Route of administration

 Shelf- life

 Batch number

 Storage pre-cautions

 Directions for use

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Thank You!!!!!!!!!!!

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