Introduction:
The use of liquid pharmaceuticals has been justified on the basis of ease of administration and rapid and efficient absorption of
drug. Dosage forms meant either for internal, external or parenteral use may be sub-classified into monophasic or biphasic
liquid dosage forms. The monophasic liquid dosage forms consists of either true or colloidal solutions or solubilised system. All
these consists of only a single phase and may have either aqueous or non-aqueous solvents as the base. Biphasic dosage forms
are represented by emulsions and suspensions and consist of two immiscible phases, the continuous phase and the dispersed
phase. The continuous phase in both is a liquid, the dispersed phase in emulsions is also a liquid while in case of suspensions,
the dispersed phase consists of a finely divided solid.
Advantages and Disadvantages: Refer to your copy which is written in class.
Classifications of liquid dosage forms
Suspension: 0.5 to 5 microns
Emulsion: 0.25 to 25 microns
For a typical oil-in-water emulsion, creaming can only occur if the oil
droplets are smaller than ~1 micron (at which point Brownian motion
takes over).
Excipients used in the formulation of liquid dosage forms
a) Sweetening agents
• Saccharin is a sucrose substitute for diabetics, the obese, and others who do not wish to
ingest sucrose. It is commonly found in its sodium salt form, which is more palatable than
saccharin and comparatively free of unpleasant after taste. Sodium cyclamate is another
synthetic sweetening agent that is approximately 30 times as sweet as sugar. However, its
use as an artificial sweetener is banned in the U.S.A. because of the possible toxicity of its
metabolite cyclohexylamine. Aspartame, is 200 times sweeter than sucrose and, unlike
saccharin, has no aftertaste. Its aqueous solubility is adequate for formulation purposes. It is
stable in the solid form, but its stability in solution depends on temperature and pH.
• Newer non-caloric sweetening agents have come to market in the last decade.
Sucralose (Splenda) is approximately 600 times sweeter than sucrose and differs from
sucrose by the substitution of three chlorines for hydroxyl groups. Sucralose is heat
stable and stable over a wide pH range affording its utility in formulations prepared at
high temperatures. Acesulphame-K is approximately 200 times sweeter than sucrose
and is commonly used concomitantly with aspartame to synergistically enhance overall
sweetening. This sweetener is also heat stable. Furthermore, Monoammonium
glycyrrhizinate has even been used in liquid oral preparations
• Sucrose is the most widely used sweetener, with a long history of use. It is a why crystalline powder,
soluble in water and alcohol. Official simple syrup is an 85%w/V solution of sucrose in water. During
the preparation of sucrose solution, care should be taken to avoid charring and caramelization caused
by heat. Sucrose is chemically and physically stable in the pH range of 4.0-8.0. It is frequently used in
conjunction with sorbitol, glycerin, and other polyols, which reduces its tendency to crystallize. One of
the sucrose crystallization manifestations is "cap-locking," which occurs when sucrose crystallizes on
the threads of the bottle cap and interferes with the opening.
b) Viscosity controller agents
• It is sometimes desirable to increase the viscosity of a liquid, either to serve as an adjunct for
palatability or to improve pourability.
c) Buffers
• During storage of liquid preparations, degradation of the product, interactions with container
components or dissolution of gases and vapors causes change in their pH level, which can be prevented
by addition of buffer. A suitable buffer system should have adequate buffer capacity to maintain the pH
level of the product. Commonly used buffer systems are phosphates, acetates, citrates, and glutamates.
Although buffers ensure pH stability, the buffer system can affect other properties such as solubility and
stability. The ionic strength contributions of the buffer systems can affect stability. Buffers can also act
adversely as general acid or general base catalysts and cause degradation of the drug substance.
Therefore, before selecting any buffer system, the effect of buffer species should be studied.
d) Antioxidants
e) Preservatives
• Various drugs in solution are subject to oxidative
degradation. Oxidation is defined as a loss of
electrons from a compound leading to change in
the oxidation state of the molecule. Such reactions
are mediated by free radicals or molecular oxygen,
and are often catalyzed by metal ions. Moreover,
oxidation often involves the addition of oxygen (or
other electronegative atoms like halogens) or the
removal of hydrogen.
SOLUBILITY ENHANCEMENT TECHNIQUES
E.g.: Micronization of poorly aqueous soluble, but non-hydrophobic drugs
such as griseofulvin and chloramphenicol results in enhanced solubility.
