Liquid Dosage Forms.pptx

LIQUID DOSAGE
FORMS
PREPARED BY:
Bhargavi Mistry
[Assistant Professor, School of
Pharmacy Rk University]
B. Pharm SEM 3
(Pharmaceutics I)

2
LIST OF
CONTENT
Prepared by: Bhargavi Mistry
1) Introduction
2) Advantages & disadvantages
3) Classification of liquid dosage forms
4) Excipients used in liquid dosage forms
5) Solubility enhancement techniques
6) References
7) Questions

 Liquid:
A liquid is a nearly incompressible fluid that conforms to the shape of its
container but retains a (nearly) constant volume independent of pressure.
 Liquid dosage forms are one class of dosage forms, which are meant for either
internal, external or parenteral use.
 Liquid dosage forms are mostly preferred by children and infants who find
difficulty in swallowing solid dosage forms. No doubt, they lack the stability
parameter of active drugs, but they are very much popular amongst prescription of
doctors in lieu of their other aesthetic properties.
 Liquid dosage forms are prepared by dissolving active ingredient (s) in an
aqueous or nonaqueous solvent, by suspending the drug (if the drug is insoluble in
pharmaceutically or therapeutically acceptable solvents), or by incorporating the
drug (s) into one of the two phases of an oil and waters systems.
INTRODUCTION
3

ADVANTAGES
(1) Drug is rapidly available for absorption.
(2) They are the most suitable dosage forms for infants, children, geriatric, and mentally
disturbed patients.
(3) They are suitable for those drugs which create irritation in GIT if given in dry forms e.g.
bromides and iodides.
(4) In case of homogeneous solutions they assure uniformity of dosage.
(5) Doses can easily be varied as per the requirement of the patients;
(6) Bitter and obnoxious drugs can be given in sweetened, colored, and flavored vehicles.
(7) Hygroscopic and deliquescent medicaments which are not suitably dispensed in solid
dosage forms can easily be given in liquid dosage forms.
(8) Because of their aesthetic properties, they create good appeal and beneficial psychological
effect on patients.
4

DISADVANTAGES
(1) Liquid dosage forms are bulky and therefore inconvenient to carry, transport and store.
(2) The stability of medicament(s) in aqueous system is poorer than if they were formulated as
solid dosage forms, particularly when the medicaments (s) are susceptible to hydrolysis.
(3) Two incompatible drugs cannot be given together as it is possible in case of solid dosage
forms.
(4) There are chances of variation in the doses since patients use the measure at the time of
taking dose. Sometime they might be in hurry and do not bother the accuracy of the dose.
(5) Liquids provide suitable media for the growth of micro-organisms and therefore, require
suitable preservatives.
(6) Pleasant taste, sometimes becomes hazardous amongst the children since there might be
chances of over dosage.
(7) Accidental breakage of the container, it may result in loss of the whole of the dosage form.
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LIQUID DOSAGE FORMS
MONOPHAS
IC
For
oral use
For external
use
For
special use
Use in oral
cavity
Used in other than
oral cavity
parenteral
BIPHASIC
Liquid in
liquid
Oral use External use
Parenteral
use
Solid in
liquid
Parenteral
use
Ophthalmi
c use
Oral use
External
use
[Liquid in liquid/ solid
in liquid]
Simple Mixture
(solution)
Draughts
Drops
Linctuses
Syrups
Elixirs
Liniments
colloidons
Mouth wash
Gargles
Throat spray
Throat Paints
Douches
Enemas
Eye lotion
Eye drops
Ear drops
Nasal drops
[Emulsion] [Suspension]
CLASSIFICATION
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EXCIPIENTS USED IN
LIQUID DOSAGE FORM

EXCIPIENTS USED
 To formulate any liquid dosage form, apart from the drug(s), a formulator requires many other additives
which do not have any pharmacological action but are added to impart fluidity, palatability, stability,
and good appearance.
 There are many additives that have been utilized for the design of a stable liquid dosage form.
They are as follows:
1) Surfactant 4) Stabilizers
2) Hydrocolloids 5) Coloring agents
3) Vehicles 6) Sweetening agent
8

SURFACTANT
 Surfactants are defined as compounds that lower the interfacial tension between the two
immiscible phases thus, make two immiscible liquids, miscible to each other or dispersing
poorly wettable drugs to a solvent system.
 Each surfactant molecule possesses two parts; a polar part and nonpolar part. They are
oriented at the interphase according to the polarity of the end. Polar goes towards the polar
liquid (water) while nonpolar part goes towards the nonpolar liquid (oil) and thus lowers the
interfacial tension between water and oil.
 At a certain concentration, surfactants (of proper HLB values) forms micelles in the bulk of the
liquid and enhance the solubility of the poor! soluble drugs.
Examples: Sodium lauryl sulphate(SLS), Sodium cetyl sulphate, Benzalkonium
chloride, Glyceryl monostearate.
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10

HYDROCOLLOIDS
 Hydrocolloids are high molecular weight solid substances used to increase the
viscosity of the aqueous system, as emulsifying and suspending agents. They are
known as gums and consist of polysaccharides and proteins.
 Most hydrocolloids are more soluble a hot water than in cold water and tend to
precipitate or form a gel on cooling.
E.g. agar and gelatin.
 Some are more soluble in cold water than in hot water.
E.g. methyl cellulose, hydroxy propyl methyl cellulose(HPMC)
11

Hydrocolloids are classified on the basis of their sources:
1) NATURAL:
They are obtained form plant animal and mineral.
E.g. Acacia, Tragacanth, agar (from the plant), Gelatin and Casein (from an animal),
Colloidal silica, Colloidal alumina, Bentonite (Mineral source)
2) SEMI-SYNTHETIC:
They are obtained by chemical modification of cellulose of wood, pulp or cotton and
produce
soluble polymers.
E.g. Methyl cellulose, Hydroxyethyl cellulose and Hydroxy propyl cellulose
3) SYNTHETIC:
They are obtained by chemical synthesis.
E.g. Carbopol, polyox
12

VEHICLES
 A carrier or inert medium used as a solvent (or diluent) in which the medicinally active
agent is formulated and or administered.
 Water is the most common vehicle for liquid preparation.
 Other than water there are some aromatic waters, elixirs, infusions, decoctions and
syrups which form the vehicle for the other oral preparations.
VEHICLE USE
1) WATER
Purified water For all liquid preparation except
parenteral preparation
Water for injection For parenteral preparation
Sterile water for injection For parenteral preparation
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VEHICLE USE
2) OILS
Corn oil Solvent and vehicle for injection
Cottonseed oil Solvent and vehicle for injection
Peanut oil Solvent for injcetion
3) ALCOHOL
Ethanol Solvent and cosolvent (elixir, lotion)
Propylene glycol Solvents (syrup, elixir)
Glycerol Solvent and cosolvent for many oral
preparations
4) AROMATIC WATERS As vehicle in many oral preparations
5) ELIXIRS As vehicle in some oral preparations
6) SYRUPS As vehicle in many oral preparations 14

STABILIZERS
 Stabilizers are the materials which stabilize the pharmaceutical preparations if they
are to be kept as such for longer period of time.
 As the time passes, there are chances of some factors which might affect the
stability of preparations like; microbial growth, oxidation, change in pH etc. To
avoid these types of changes during the shelf life of the formulation, stabilizers
like; preservatives, antioxidants and buffers are to be added respectively.
 Antioxidants for aqueous systems
1) Sodium sulfite
2) Sodium metabisulfite
3) Thioglycerol
4) Ascorbic acid
 Antioxidants for oily systems
1) Ascorbyl palmitate
2) Hydroquinone
3) Propyl gallate
4) tocopherol
15

 The rate of oxidation is enhanced by heavy metal ions which enhance the drug degradation. A required
amount of sequestering agent (complexing agent) is added to form the complexes with heavy metals thus
avoid oxidation.
E.g. EDTA( Ethylene Diamine Tetraacetic Acid)
 Change in the pH of the liquid preparations up to a certain limit can be avoided by adding buffers that
maintain the pH of the liquids for the required period of time.
Hydrochloric acid buffer (pH - 2.2 to 2.0), neutralized phthalate buffer (pH 4.2 to 5.8),
phosphate buffer (pH-5.8 to8.0), alkaline borate buffer (pH 8.0 to 10.0).
The selection of any stabilizer is based on many factors like; Drug and additives compatibility, physiological
acceptance, its own stability, compatibility with package materials, etc. Therefore, a formulator must keep
these points in his mind while developing any liquid formulation.
16

COLOURING AGENTS
 Coloring agents are added to the liquid preparations to improve their organoleptic
properties.
1) To increase their acceptability to patients: e.g; colored tonics and cherry— red
cough mixturesare liked by children.
2) For Identification: e.g; anesthetic trichloroethylene, which may be colored blue
to distinguish it from chloroform, which resembles its physical characteristics.(3)
3) To produce standard preparations: e.g. natural calamine which is for
pharmaceutical purposes is not constant in color and has been replaced by
artificially prepared material tinted with Ferric oxide.
4) To maintain uniformity and establish a brand name: e.g. the liquid
preparation of one company must maintain uniformity with regard to colors to
establish the brand name in the market. e.g.; Dabur’s ‘Lal Tel’, red in color.
17

 Colors are classified on the basis of the sources from which they are obtained;
(1) Mineral color:
Nowadays rarely used. They are replaced by synthetic colors. The important colors of this class are
ferric oxide, lead chromate, Prussian blue, vermillion, etc.
(2) Plant and animal colors:
Colors from plant sources are alizarin, indigo, chlorophyll, carotenoids, anthocyanins, and
flavones.
The only color from animal sources is cochineal
(3) Synthetic colors:
Synthetic colors are not fit for pharmaceutical dosage forms because of their toxicity. The first
synthetic color discovered accidentally was “mauveine” know as perkin’s purple. Thereafter
major industries grew up for the manufacturing of coal tar colors Many coal tar colors have been
found:
e.g. Naphthol blue black 20470, brilliant blue FCS 42090, fast green FCF 42053, Orange G
16230, Amaranth I.N. 16185, sunset yellow FCF 15185.
18

FLAVORING AGENTS
 These are the most important agents to be added to the pharmaceutical oral
preparation because the patient's choice of preparation is the ultimate goal. It might
have become an important factor in the sale of the product.
 Initially, some natural flavors such as clove, eucalyptus, lemon, mint, orange,
wintergreen, etc., were very common for preparations meant for oral
administration, and flavors such as jasmine, lavender, rose, etc., for preparations
meant for external use.
 But nowadays, a complete approach is changed to select a flavor. It is evaluated
with reference to the drug or vice-versa, for its taste, mouth effects and overall
impression on the formulation.
19

TASTE FLAVOURS
Alkaline Mint, chocolate, vanilla
Sour (acid) Lemon, orange, anise, raspberry,
strawberry
Bitter Anise, mint, fennel, chocolate, cherry
Metallic Grape, lemon
Salty Citrus, maple, raspberry, fruity
Sweet Fruity, vanilla, maple, honey
COLOUR FLAVOURS
Pink to red Cherry, raspberry, strawberry, apple, rose
Brown Chocolate, honey, caramel, walnut
Yellow to orange Lemon, lime, orange, cherry
Green Mint, banana, pistachio
White to off white Vanilla, banana, jasmine, mint, spearmint
Violet to purple Grape, liquorice
Blue Mixed fruit, plum, blueberry, liquorice
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SWEETENING AGENTS
 The purpose of a sweetening agent is to mask the disagreeable taste of the
formulation and impart the sweet taste.
 The most popular sweetening agent is sucrose, which is stable at pH between 4.0
to 8.0 and generally used along with glycerin or sorbitol to avoid its tendency to
get crystallized.
 The use of these sweetening agents must be done on the basis of their physical and
chemical properties, relative sweetness, aftertaste, and toxic effects. Henceforth, a
pharmacist must use the sweeteners after going through their literature and law.
 E.g: Sorbitol, Dextrose, sucrose, saccharine, Glycyrrhizin
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SOLUBILITY ENHANCEMENT
TECHNIQUES

SOLUBILITY
 Solubility:
The extent to which the solute dissolves at a particular temperature is known as
its solubility at that temperature.
Usually, 20°C is considered to be the optimum temperature for the preparation of
stable saturated solutions because it is considered as room temperature at which the
drug are supposed to be kept.
23

 To summarize, a few generalizations have been framed to predict the solubility of
compounds. They are as follows:
1) More Similarity in the structure of solute and solvent enhances the solubility the of solute in
that solvent.
2) Polar solutes dissolve in polar solvents while nonpolar solutes dissolve in non-polar
solvents.
3) Addition of nonpolar groups like -OH, -CHO, -CHOH, -CH2OH, -COOH, -NH2 etc., tends
to increase the solubility of organic compounds in water.
4) Addition of nonpolar groups tends to decrease the solubility of compounds in water.
5) Introduction of halogen groups tends to decrease the solubility while the branching of chains
increases the solubility in water.
6) Solid compounds of high molecular weights are generally more difficult to dissolve in water.
24

 There are few techniques available in the solution technology to enhance the solubility of
poorly soluble compounds,
 They are as follows:
1) Solubilization
2) Co-solvency
3) pH modification
4) Complexation
5) Hydrotrophy
6) Chemical modification
25

SOLUBILIZATION
 This technique was introduced by Mc Bain in 1937. It is the dissolution of poorly soluble
solute molecules in water in presence of surfactants and forms a thermodynamically
stable solution.
 The process of dissolution in presence of surfactants has been described as the formation
of micelles (colloidal aggregate of surfactant), which enhances the solubility of poorly
soluble solute, when surfactant of proper HLB is added in low concentration to liquid,
it tends to orient at the air-liquid interface.
 If the surfactant is continued to be added in higher concentrations, the air-liquid
interface is fully occupied.
 At still higher concentrations, the surfactant molecule is maintained in the system, and
aggregates of surfactant are formed called micelles.
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Surfactant Surfactant
(a) Surfactant in low concentration
(b) Surfactant in high concentration
(c) Surfactant in the concentration of CMC

 The concentration of surfactant at which micelles formation takes place is called critical
micelle concentration (CMC). Micelles may be of various shapes like spherical, sausage, rod,
or lamellar.
 Micelle formation increases the solubility of a solute by virtue of its dissolving in or being
absorbed on micelle.
 This function of surfactant starts only at CMC and increases with the concentration of the
micelles.
Example:
Solubility enhancement of cresol solution with the soap solution.
As such cresol has only 2% v/v solubility in water but with soap solution, we can dissolve it
up to 50% v/v cresol in water.
 This technique is useful to solubilize many water-insoluble vitamins like Vit. A, D
and K.
28

COSOLVANCY
 This technique enhances the solubility of the very poorly soluble drug in water by adding
water-miscible solvents in which the drug is very soluble.
 The solvents used in combination to increase the solubility of the drug solute are known
as co-solvents.
Examples: Ethanol, sorbitol, glycerin, propylene glycol, and polyethylene glycols.
 Aromatic waters are usually prepared by using this technique in which ethanol has been
used as a cosolvent
Examples: Cinnamon water, Dill water, Camphor water.
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pH MODIFICATION
 pH is helpful in enhancing the solubility because many drugs behave as either weak acids
or weak bases.
 For example, solubility of phenobarbitone varies at different pH values:
pH 2.6 7 8 9 10
Solubility 0.11 0.17 0.41 1.4 2.9
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COMPLEXATION
 Many organic compound in solution tend to associated with each other to some extent.
 Every substance has specific reproducible equilibrium solubility in a particular solvent at
a given temperature. Any change in this equilibrium denotes the formation of new
species in the solution.
 In carse of weak acids and bases, the total solubility is equal to inherent solubility of
undissociated compound plus the concentration of the dissociated species.
 Similarly when complexes are formed, the total solubility is equal to the inherent
solubility of the uncomplexed drug plus the concentration of the drug complex in the
solution.
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 Suppose D is the drug and C is a complexing agent, both combine together and form
complex:
xD + yC (Dx Cy)
(Drug) (complexing agent) (complex)
 The total solubility can be denote as follows:
S = [D] + X[DxCy]
Where,
[D]: The solubility of uncomplexed drug
X[DxCy]: Concentration of drug in complex form
T
32

HYDROTROPHY
 When the solubility of the drug is enhanced owing to the presence of a large amount of
additives, the technique is referred to as hydrotrophy.
 Mechanism of this technique is not known but it has been speculated that this change in
the solubility of drug in solution might be either due to solubilization, complexation or
change in the solvent character.
 Example:
Enhancement of Caffeine solubility in water due to presence of large concentration of
sodium benzoate.
 The technique is hardly useful in practical since it requires large amount (in the range of
20% to 50%) of additives to show modest increase in the solubility.
33

CHEMICAL MODIFICATION
 This is the ultimate technique to enhance the solubility of many poorly soluble drugs by
modifying them into their water soluble derivatives.
 Example:
Solubility of betamethasone alcohol in water which is 5.8 mg/100 ml at 25° C; but the
solubility of its 21 disodium phosphate ester is greater than 10 g/100 ml at 25°C: nearly
about 1500 times increase in solubility.
Other example is the enhancement of solubility of alkaloids in water if converted to
their salts.
34

REFERENCES
1) Dr. A.K. Seth, A textbook of pharmaceutics, 2nd edition 2022, Pee Vee publication,
Page no. 238 – 272
2) Dr. G. K. Jani, Pharmaceutics 2, 6th edition, B. S. Shah Prakashan, Page no. 165-178
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QUESTIONS
1) Write the advantages and disadvantages of the liquid dosage form.
2) Discuss the role of various excipients used in the formulation of the liquid dosage form.
3) State the significance of the solubilization technique for enhancement of solubility.
4) Enlist the solubility enhancement technique. Explain any two in detail.
5) Give the classification of liquid dosage forms.
6) Define the following terms: Co-solvent, Solubility, Hydrocolloids, Surfactant
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THANK YOU

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