Liquid Dosage Forms

The use of liquid pharmaceuticals has been justified based on ease of administration and rapid and efficient absorption of the 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 consist of either true or colloidal solutions or solubilized system. All these consist 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 the case of suspensions, the dispersed phase consists of a finely divided solid. The classification of the liquid dosage forms is given in Fig. and the comparison of characteristics of various liquid dosage forms are shown in Table.

Classification of Liquid Dosage Forms
Fig: Classification of Liquid Dosage Forms
Comparison of characteristics of various liquid dosage forms
Table: Comparison of characteristics of various liquid dosage forms

Advantages of Liquid Dosage Forms:

The presentation of drugs as liquid dosage form offers the following advantages:

(i) The drug is more readily available for absorption from liquid dosage forms as compared to the solid dosage form. By providing the drug in solution, the dissolution phase of the absorption process can be surpassed, providing a faster therapeutic response.

(ii) The doses of drugs can be easily adjusted according to the need of the patient. If the dose of the active ingredient is to be altered, a simple adjustment to the quantity of solution to be taken is all that is required.

(iii) Liquids are easier to swallow than tablets or capsules and are therefore especially suitable for children, the elderly, intensive care, and psychiatric patients.

(iv) Gastric irritation due to certain drugs like potassium chloride and when administered as a solid dosage form is avoided or reduced on administration as a liquid dosage form because of the immediate dilution by gastric content.

(V) Drugs with large doses can be easily administered in a liquid dosage form.

(vi) Distribution of drugs in liquid dosage forms is better than solid dosage forms.

(vii) Liquid dosage forms are more economical to produce than solid dosage forms.

(viii) Liquid dosage forms can be designed to administer via several routes. Parenteral preparations, douches for vaginal use, cutaneous (for use on skin) preparations, and ophthalmic preparations can all be liquids.

Disadvantages of Liquid Dosage Forms:

There are also some disadvantages associated with the use of liquid preparations:

(i) Drugs are usually less stable in liquid dosage forms as compared to solid dosage forms like tablets and capsules, particularly if they are susceptible to hydrolysis.

(ii) Liquids, especially aqueous preparations, are susceptible to microbial contamination.

(ii) Masking the unpleasant taste of a drug in solution is more difficult than when the drug is in a solid dosage form.

(iv) Liquid preparations are usually bulky and therefore inconvenient to store and carry. Liquid dosage forms are always much larger and bulkier than solid formulations. Coupled with this is the fact that pharmaceutical liquids are packed in glass bottles, which are prone to breakage.

(V) Administration of the correct dose is less precise since it depends on the ability of the patient to measure the correct dose using a suitable measuring device such as a spoon or a dropper.

(vi) Measuring device is to be supplied to the patients for accurate dose administration. This will have cost implications and in addition, counseling is required for its use.

(vii) Suspensions and emulsions have the added drawback that they must be thoroughly shaken to allow accurate dosing.

Excipients used in Formulation of Liquid Dosage Forms:

Sweetening agent:

Sweeteners are indispensable components of many liquid oral dosage forms, especially those containing bitter or other unacceptable tastes. Sweetening agents may comprise large portions of solid content in most liquid oral dosage forms. Sweeteners are often classified as either nutritive (caloric) or non-nutritive (non-caloric). Non-caloric sweetening agents are preferred for diabetic patients, as ingestion does cause an increase in systemic glucose concentrations. Some of the most commonly used sweeteners include sucrose, sorbitol, mannitol, liquid glucose, honey molasses, saccharin, aspartame, sucralose, and acesulphame-K.

Viscosity controlling agents:

It is sometimes desirable to increase the viscosity of a liquid, either to serve as an adjunct for palatability or to improve pourability. This can be achieved by increasing the sugar concentration by incorporating viscosity controlling agents such as polyvinylpyrrolidone or various cellulosic derivatives (e.g., methylcellulose or sodium carboxymethylcellulose). These compounds form solutions in water that are stable over a wide pH range. Methylcellulose and carboxymethylcellulose are available in several different viscosity grades. Carboxymethylcellulose may be used in solutions containing high concentrations of alcohol (up to 50%) without precipitating. It is precipitated, however, as an insoluble salt of several multivalent metal ions such as AT++, Fe+++, and Ca++.  Methylcellulose polymers do not form insoluble salts with metal ions but can be salted out of solution when the concentration of electrolytes or other dissolved materials exceeds certain limits. These limits may vary from about 2 to 40%, depending on the electrolyte and the type of methylcellulose involved.

Viscosity-inducing polymers should be used with a degree of caution. They are known to form molecular complexes with a variety of organic and inorganic compounds, and in so doing, influence the activity of these compounds. It is conceivable that highly viscid systems that resist dilution by gastrointestinal fluids might impede drug release and absorption.


During storage of liquid preparations, degradation of the product, interactions with container components, or dissolution of gases and vapors causes a change in their pH level, which can be prevented by the 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.


Various drugs in solution are subject to oxidative degradation. Oxidation is defined as a loss of electrons from a compound leading to a 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. Drugs possessing favorable oxidation potential are especially vulnerable to degradation. Agents with an oxidation potential lower than that of the drug in question are called antioxidants.


Flavoring can be divided into two major categories: selection and evaluation. Much has been written on both phases of pharmaceutical flavoring, but selection remains an empiric activity.

The four basic taste sensations are salty, bitter, sweet, and sour. Some generalizations concerning the selection of flavors to mask specific types of taste have been suggested by Janovsky and by Wesley. (Table)

Table: Flavour Selection

A combination of flavouring agents is usually required to mask these taste sensations effectively. Menthol, chloroform, and various salts frequently are used as flavour adjuncts. Menthol and chloroform are sometimes referred to as de-sensitizing agents. They impart a flavour and odour of their own to the product and have a mild aesthetic effect on the sensory receptor organs associated with taste. Monosodium glutamate has been widely used in the food industry, and to a lesser extent, in pharmaceuticals, for its reported ability to enhance natural flavours.


In recent years, adequate preservation of liquid products has increased in importance. Reports of clinical complications arising from microbial contamination of oral and topical products have originated in several European countries and the United States. Numerous product recalls and tightened regulatory and compendia limits have re-emphasized the need for a die formulator to carefully and thoroughly consider all aspects of the preservative system chosen for a particular formula. In addition to presenting a health hazard to the user, microbial growth can cause marked effects on product stability.

Numerous sources of contamination exist. Including among these are raw materials, processing containers and equipment, the manufacturing environment operators, packaging materials, and the user.

Manufacturing techniques to minimize microbial contamination are presented under the heading “Manufacturing Considerations.” The remainder of this section deals with preservative systems for liquid products.

An ideal preservative can be qualitatively defined as one that meets the following three criteria:

1. It must be effective against a broad spectrum of microorganisms.

2. It must be physically, chemically, and microbiologically stable for the lifetime of the product.

3. It must be non-toxic, non-sensitizing, adequately soluble, compatible with other formulation components, and acceptable for taste and odor at the concentrations used.

No single preservative exists that satisfies all of these requirements for all formulations. The selection of a preservative system must be made on an individual basis, using published information and “in-house” microbiologic studies for guidance. Frequently, a combination of two or more preservatives is needed to achieve the desired antimicrobial effect.

The antimicrobial agents that have been used as preservatives can be classified into four major groupings: acidic, neutral, mercurial, and quaternary ammonium compounds.

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