Pharma gyan Pandit

LIQUID DOSAGE FORMS

I. Definition 

Liquid dosage forms are prepared by dissolving the active ingredient(s) in an aqueous or nonaqueous solvent, by suspending the drug in appropriate medium or by incorporating the drug substance into one or two phases of an oil and water system.

These forms can be formulated for different routes of administration: oral use, introduction into body cavities, or applied externally.

The oral liquid forms can be readily administered to children or people unable to swallow tablets or capsules.

The absorption rate of oral dosage forms decreases in the following order:

aqueous solution > aqueous suspension > tablet or capsule 

Drug substances are less stable in aqueous media, than in the solid dosage forms and it is important to properly stabilize and preserve them. There is a risk of chemical interactions and microbial contamination for some of the products.

II. CLASSIFICATION 

1.  Solutions 

Þ  aqueous solutions

Þ  nonaqueous solutions

2.  Emulsions

3.  Suspensions 

4.  Mucilages 

5.  Liniments 

6.  Infusions and decoctions 

7.  Drops 

8.  Mixtures

9.  Sterile dosage forms for injection

Þ  ampoules 

Þ  vials 

Þ  bottles 

Þ  prefilled disposable syringes 

II. PROPERTIES 

SOLUTIONS

Solutions are homogeneous mixtures that are prepared by dissolving a solid, liquid, or gas in another liquid. The molecules of the dissolved substance are dispersed among those of the solvent. Many pharmaceuticals are simply solutions of a medicament in water, alcohol, ether, glycerin, oils, or some other solvent. Various aromatic waters (e.g., chloroform or peppermint water) may also be used as solvents. Solutions are intended for internal, external, and parenteral administration.

1. Aqueous solutions include those pharmaceutical forms that are prepared with purified water (aqua destillata – deionized, demineralized water) or aromatic water as a solvent. Simple solutions for oral administration, douches, enemas, gargles, mouthwashes, nasal and otic solutions are assigned to this category.

2. Nonaqueous solutions are the alcoholic and hydroalcoholic solutions, ethereal solutions, glycerin solutions, etc.

Solutions may be prepared in bulk or as single-use packages, and they are usually bottled automatically (few of them can be prepared extemporally).

EMULSIONS

Emulsions are two-phase systems in which one liquid is dispersed throughout another liquid in the form of small droplets. They are classified as:

Þ   oil-in-water (O/W) emulsion  – oil is the dispersed phase and an aqueous solution is the continuous phase

Þ   water-in-oil (W/O) emulsion  – an aqueous solution is the dispersed phase and oil is the continuous phase

These forms can be administered orally, topically, or parenterally (intramuscularly). Specialized uses include emulsions for intravenous feeding of lipid nutrients (Intralipid). Other radiopaque emulsions are used as diagnostic agents for X-ray examinations.

Emulsions are thermodynamically unstable. They appear white and tend to separate on standing. In order to prepare suitable emulsions and to have them remain stable for a suitable period of time, a number of emulsifying agents are used in their preparation. They can be natural substances (acacia or Gumma arabicum, tragacanth, pectin, gelatin, egg yolk, lecithin, etc.), finely divided solids, or synthetic agents.

SUSPENSIONS

Suspensions are two-phase systems consisting of a finely divided solids dispersed in liquids. If the drug is insoluble or poorly soluble, a suspension may be the most suitable dosage form. The taste of drugs can be improved if they are supplied in suspension form rather than solutions. Suspensions may be formulated for oral, parenteral (intramuscular or intraarticular) or topical administration. Antibiotic granules are generally used for preparation of suspensions in pediatric practice.

Well formulated suspensions should posses certain basic properties. The dispersed phase should settle slowly, if at all possible, and be dispersed readily on shaking.

The main ingredients in a suspension are:

·        a drug

·        natural viscosity agents (natural gums and cellulose derivatives)

·        an external medium  – it is usually water for oral preparations; or other polar liquids (glycerin, alcohol)

MUCILAGES

Mucilages are thick, viscid, adhesive liquids, produced by dispersing gum in water, or by extracting the mucilaginous principles from plant substances with water (Gumma arabicum, Radix althaeae, etc.). They are unstable and should never be made in quantities larger than those that can be used immediately, unless a preservative is added.

Mucilages are used primarily to prevent immediate sedimentation of insoluble substances in liquids. They can prevent mucous irritation caused by some drug substances (e.g., Chlorali hydras).

INFUSIONS AND DECOCTIONS

Infusion is a dilute solution of the readily soluble constituents of crude drugs (from the soft parts of plants). Fresh infusions are prepared by macerating the drugs for a short period of time (15 min) with boiling water.

Decoction are extracts of the water-soluble and heat-stable constituents from crude drugs (from the hard parts of plants) by boiling in water for 30 min, and cooling.

These forms are of short duration and should never be administered in quantity for more than 3 days.

DROPS

Drops are solutions, tinctures, or mixtures of high-potent drug substances. These forms are intended to be administered internally or externally (as eye drops or collyrium, nasal, and otic drops). Drops are prescribed in small quantity (10  – 30 g). For officinal forms, the right number of drops per 1 ml of liquid have to be labeled.

MIXTURES

Mixtures are multicomponent liquid containing two or more active ingredients, dissolved, suspended, or dispersed in a suitable liquid base (water, alcohol, glycerin, aromatic water, or infusions and decoctions). Some mixtures may contain tinctures. Suspended solids may separate slowly on standing, but are easily redispersed on shaking (shake mixtures  – mixturae agitandae).Syrups are added as Remedium corrigens, in quantity of 20% of the total volume (30% for children). Mixtures are unstable dosage forms with short duration and they are subject to contamination by microorganisms during the period of their use.

Sterile dosage forms for injection

Sterile dosage forms for injection differ from all other drug dosage forms because of their unique use for injection directly into body tissue through the primary protective systems of the human body, the skin and mucous membranes. Therefore, they must be exceptionally pure and free from contaminants.

Injections may be classified in several categories:

1.  Solutions ready for injection

2.  Dry, soluble products ready to be combined with a solvent just prior to administration (ex tempore)

3.  Suspensions ready for injections

4.  Emulsions

5.  Liquid concentrates ready for dilution prior to administration

These injections may be administered by such routes as intravenous, subcutaneous, intradermal, intramuscular, intraarticular, and intrathecal. The nature of the product will determine the route of administration. Suspensions would not be administered directly into the blood stream because of the danger of insoluble particles blocking capillaries. Unstable emulsions, if injected intravenously may cause lipid embolism (excluding some forms with special characteristics). Hypertonic solutions are administered only intravenously. When compared with other dosage forms, injections possess certain advantages:

1.  They provide drugs for immediate action

2.  The therapeutic dose is adjusted more accurately and readily

3.  Drugs can be administered parenterally in cases of unconscious or uncooperative state of the patient, or because of lack of absorption from the GIT.

Among the disadvantages are requirement of asepsis, pain factor, risk of local irritation, difficulty in correcting the error.

Parenteral products are packaged in ampoules, vials, bottles, plastic bags, and prefilled disposable syringes. Containers for injections can be made of glass or thermoplastic polymers. They may range in size from 1000 ml bottles to 1 ml or less ampoules, vials, or syringes. Each vial is sealed with a rubber closure held in place by an aluminum cap.

The most widely used solvent for parenteral preparations is sterile water for injection (aqua redestillata or bidestillata – pyrified water rendered sterile and pyrogen-free by repeated distillation). Other common solvents include sodium chloride injection, peach oil (for water-insoluble drugs), etc.