Liquid Dosage Forms

Liquid dosage forms are pharmaceutical preparations in a liquid state that are administered orally, topically, or by injection. They contain a mixture of active drug components and non-drug components (excipients) dissolved or suspended in a suitable solvent or mixtures of solvents. They are designed to provide the maximum therapeutic response in a target population with difficulty swallowing solid dosage forms and/or to produce rapid therapeutic effects.

Table of Contents

Advantages

Suitable for patients who have difficulty swallowing tablets or capsules, such as pediatric or geriatric patients.
Attractive appearance and beneficial psychological effects.
Drugs with bitter and unpleasant taste can be given in sweetened, colored, and flavored vehicles.
Higher flexibility in dosing compared to solid dosage forms.
Rapid availability for absorption than tablets and capsules.
Suitable for administering hygroscopic and deliquescent medicaments.
Certain products like adsorbents and antacids are more effective in liquid dosage form.

Disadvantages

More susceptible to chemical degradation compared to solid dosage forms.
Bulky and therefore inconvenient to transport and store.
Accidental breakage of the container results in loss of whole dosage form.
Shorter shelf-life due to low stability.
Often provides suitable media for microbial growth and may require the incorporation of a preservative.
May require special storage conditions.
The taste of a drug is usually more prominent when in solution than in a solid form.
Higher chance of dose variability.

Liquid dosage forms are broadly classified into two groups.

Monophasic Liquid Dosage Forms

These are one-phase systems consisting of two components, solute (the component that gets dissolved) and the solvent (the medium in which solute dissolves). They are further classified into liquids for oral use (e.g., mixtures, linctuses, draughts, elixirs, syrups, and drops), liquids for external use (e.g., lotions, liniments and collodions), and liquids for special use (e.g. gargles, mouthwashes, throat paints, eye drops, eye lotions, ear drops, nasal drops and sprays, douches, enemas, inhalations and aerosols).

For oral use

Mixtures: These are liquid preparations meant for oral administration, in which medicaments are dissolved, suspended, or dispersed in a suitable vehicle. They are usually dispensed in a bottle with several doses.
Linctuses: These are viscous oral preparations generally prescribed for the relief of cough. They contain a high concentration of syrup and other ingredients that are demulcent, sedative, and expectorant. They are taken in small doses, sipped, and swallowed slowly without diluting to maximize the effect of medicaments.
Draughts: These are liquid oral preparations which contain only one or two large doses. The volume of the formulation is usually larger than that generally utilized in traditional mixture formulations and each dose is supplied in separate bottles.
Elixirs: These are clear, sweetened hydroalcoholic solutions intended for oral use. They are usually flavored to enhance their palatability. Non-medicated elixirs are employed as vehicles and medicated ones are used for the therapeutic effect of medicinal substances.
Syrups: These are viscous oral liquids that contain one or more active ingredients in solution. The base generally contains large amounts of sucrose or other sugars to which sorbitol may be added to inhibit crystallization or to modify solubilization, taste, and other base properties.
Drops: These are oral liquids that are prepared to take in small quantity with the help of a suitable measuring device such as a dropper. They are also used in ophthalmic preparations for treating eye conditions.

For external use

Lotions: These are pharmaceutical liquid dosage forms primarily used for external application to the skin. They are formulated to provide a therapeutic effect on the skin or to act as a protective, emollient, or cosmetic agent. Lotions are usually applied to external skin with bare hands, a clean cloth, cotton wool, or gauze.
Liniments: These are topical formulations designed for external application to the skin. They typically contain a liquid or semi-liquid mixture containing active ingredients such as medicinal compounds, oils, and/or alcohol. Liniments are commonly used to relieve pain, inflammation, and musculoskeletal conditions.
Collodions: These are liquid preparations, usually containing pyroxylin in a mixture of ether and ethanol, that are intended for application to the skin. When they are allowed to dry, a flexible film is formed at the site of application.

Liquid for special use

Gargles: These are pharmaceutical liquid dosage forms used for local treatment of the throat and oral cavity. They are primarily used to alleviate symptoms of various throat conditions such as sore throat, pharyngitis, and tonsillitis.
Mouthwashes: These are liquid solutions with pleasant tastes and odors that are used to clean and freshen the mouth. They are commonly used for dental hygiene, but certain mouthwashes with antibacterial properties can also help treat gum infections.
Throat Paints: These are specific pharmaceutical liquid dosage forms designed for localized application in cases of throat infections. These infections often manifest as sore throat, inflammation, and discomfort, and throat paints offer a targeted solution to alleviate these symptoms.
Eye Drops: These are liquid medications that you put inside your eye canal. They are commonly used for short-term treatment and can be purchased with or without a prescription. They are used to treat infection, inflammation, impacted ear wax and local anesthesia.
Eye Lotions: These are pharmaceutical preparations in a liquid state that are administered topically to the eye (principally the conjunctiva or the eyelid) for the treatment of primarily local disorders.
Ear Drops: These are liquid medications that you put inside your ear canal. They are commonly used for short-term treatment and can be purchased with or without a prescription. They are used to treat infection, inflammation, impacted ear wax and local anesthesia.
Nasal Drops and Sprays: These are pharmaceutical formulations designed for application into the nostrils. They commonly treat various nasal conditions, including nasal congestion, allergies, sinusitis, and dryness.
Douches: These are liquid medications intended for use in body cavities. While the term “douche” usually refers to vaginal solutions, they can also be used to irrigate other body cavities like the eyes, ears, and nasal passages.
Enemas: These are rectal preparations consisting of a liquid solution that is introduced into the rectum and colon through the anus. Enemas serve various therapeutic, diagnostic, or cleansing purposes and are designed to exert their effects locally or systemically.
Inhalations: These are drugs or solutions or suspensions of one or more drug substances administered by the nasal or oral respiratory route for local or systemic effect. Solutions of drug substances in sterile water for inhalation or in sodium chloride inhalation solution may be nebulized by use of inert gases.

Biphasic Liquid Dosage Forms

Biphasic liquid dosage forms are pharmaceutical preparations that consist of two distinct, immiscible phases. These two phases can be different according to their composition, density, and solubility. The two main types of biphasic liquid dosage forms are suspensions and emulsions.

Suspensions

A pharmaceutical suspension is a type of liquid dosage form that consists of solid particles (the suspensoid) finely divided and dispersed somewhat uniformly throughout a liquid medium (the suspending vehicle). The drug exhibits a minimum degree of solubility in this medium. Suspensions are used to provide a liquid dosage form for insoluble or poorly soluble drugs. They are also ideal for drugs that are unstable in an aqueous medium for extended periods of time. Such drugs are often supplied as dry powder for reconstitution at the time of dispensing.

Classification of suspensions

Suspensions can be classified based on various factors.

Based on the proportion of solid particles concentration

Diluted suspension: Contains 2 to 10% w/v solid.
Concentrated suspension: Contains up to 50% w/v solid.

Based on General classes

Oral suspensions: Administered orally, e.g., Paracetamol suspension.
Externally applied suspensions: Applied on the skin externally, e.g., Calamine lotion.
Parenteral suspensions: Administered intravenously or subcutaneously, e.g., Procaine Penicillin G & Insulin Zinc suspension.

Based on the Electro-kinetic nature of solid particles

Flocculated suspensions: The particles form loose aggregates with a network-like structure.
Deflocculated suspensions: The particles do not form aggregates.

Methods of preparation of suspensions

Direct Incorporation/Dispersion Method

In this method, the soluble components are dissolved in the proper volume of diluent (vehicle). The solid therapeutic agent is then dispersed into the vehicle by mixing. This can be facilitated by using wetting agents and suspending agents.

Precipitation Method

Suspensions can be prepared by this method in the following ways.

Organic Solvent Precipitation: The water-insoluble drug is dissolved in a water-miscible organic solvent and then the organic phase is added to distilled water under suitable conditions.
Precipitation by pH: This method applies to those drugs whose solubility is dependent on pH value.
Double Decomposition: It is a reaction in which two chemical compounds exchange ions, typically with the precipitation of an insoluble product.
Controlled Flocculation Method: This method can also be employed to formulate suspensions.

The particle size of the solid material can affect the physicochemical behavior of suspensions. For this reason, a distinction is usually made between a colloid or colloidal suspension with a particle size range of up to about 1 micron, and a ‘coarse dispersion’ with larger particles. Pharmaceutical suspensions fall across the borderline between colloidal and coarse dispersions, with solid particles generally in the range of 0.1 to 10 micrometers.

Emulsions

An emulsion in pharmacy is a liquid preparation containing two immiscible liquids, one of which is dispersed as globules (dispersed phase = internal phase) in the other liquid (continuous phase = external phase). The droplets range in diameter from 0.1 to 100 µm. Emulsions are thermodynamically unstable and are stabilized by the presence of an emulsifying agent.

Classification of emulsions

Emulsions can be classified based on various factors as follows.

Based on the nature of the internal & external phase

Oil-in-water emulsion (O/W): The oil phase is dispersed as globules throughout an aqueous continuous phase.
Water-in-oil emulsion (W/O): The aqueous phase is dispersed, and the oil phase is the continuous phase.

Based on Globules Size

Micro emulsion: Contains globules of size about 0.01 µm.
Fine emulsion: Have a milky appearance and the globules size range from 0.25 to 25 µm.

Multiple emulsions

These are emulsions whose dispersed phase contains droplets of another emulsion. They can be classified as,

Water-in-oil-in-water (W/O/W) emulsion
Oil-in-water-in-oil (O/W/O) emulsion

Based on the mode of administration

Oral emulsions e.g., castor oil, liquid paraffin
External emulsions e.g., creams
Parenteral emulsions e.g., vitamins
Rectal emulsions e.g., enema

Methods of preparation of emulsions

Mechanical Mixing

This method involves mechanical agitation or stirring to bring together the immiscible liquids (oil and water). High-speed mixing or homogenization devices often break down larger droplets into smaller, stable ones.

Phase Inversion

This method involves changing the ratio of the emulsion components to induce a phase inversion.

Dry Gum Method

In this method, the oil is first triturated with gum with a little amount of water to form the primary emulsion. The trituration is continued till a characteristic ‘clicking’ sound is heard and thick white cream is formed. Once the primary emulsion is formed, the remaining quantity of water is slowly added to form the final emulsion.

Wet Gum Method

As the name implies, in this method first gum and water are triturated together to form a mucilage. The required quantity of oil is then added gradually in small proportions with thorough trituration to form the primary emulsion. Once the primary emulsion has been formed remaining quantity of water is added to make the final emulsion.

Bottle Method

This method is employed for preparing emulsions containing volatile and other non-viscous oils. Both dry gum and wet gum methods can be employed for the preparation. As volatile oils have a low viscosity as compared to fixed oils, they require a comparatively large quantity of gum for emulsification.

Summary

Liquid dosage forms are pharmaceutical preparations in a liquid state that are administered orally, topically, or by injection. They are broadly classified into two groups: Monophasic and Biphasic liquid dosage forms. Monophasic forms are one-phase systems consisting of a solute and a solvent. Examples include mixtures, linctuses, draughts, elixirs, syrups, and drops. Biphasic forms contain two phases: an undissolved drug and a solvent system. This includes suspensions (solid in liquid) and emulsions (liquid in liquid). These formulations offer several advantages and their selection depends on factors such as patient characteristics, the nature of the drug, and the desired therapeutic effect.