After reading this article you will learn about the parental preparations of drugs.
The systemic absorption of a drug from an extra vascular site is influenced by the anatomic and physiologic properties of the site and the physicochemical properties of the drug and the drug product.
If a drug is given by the i.v. route, systemic drug absorption is considered complete or 100% bioavailable because the drug is placed directly into the general circulation. Once the drug is systemically absorbed, normal physiologic process for distribution and elimination occur, which usually are not influenced by the specific formulation of the drug.
Solutions are dispersion of solute in solvent (liquid or solid). Absorption from aqueous solution is generally very fast and complete from all sites of administration, if penetration through the tissue barrier doesn’t limit it.
Such rate limiting steps as disintegration and dissolution, due to dosage form factors, are minimal in the use of solution, e.g. Aqueous solution of Penicillin V gives higher blood levels than procaine penicillin, procaine penicillin in oil and benzathine penicillin. Solution of penicillin V is buffered with 4-5% sodium citrate to keep pH at 5.0-7.5. This solution is stable at refrigerated temperature for 5-7 days.
Besides providing an adequate bioavailability, solutions are also convenient for administration to pediatric and geriatric patients. In some instances the use of solutions is a crucial part of the drug delivery. For example, calcium must be administered as a solution in its citrate form in cases of achlorhydria, since the solid carbonate form will not dissolve sufficiently in the gastrointestinal tract without the presence of hydrochloric acid.
Suspensions provide better absorption than solid dosage forms as capsules, tablets and boluses. Suspensions are also used when a slow release of the drug is desired, as with intramuscular administration of drugs form a depot for slow release of the drug. Antacid products are most effectively administered as suspensions since suspensions provide a large surface area.
The mode of action of antacid involves both the chemical neutralization of hydrochloric acid and its physical adsorption onto the suspended particles. Dosage forms in the form of suspension are utilized for all routes of administration except IV.
Drugs formulated for IV administration provides 100% bioavailability and the onset of action is also rapid. Following IV administration the drug enters the blood stream directly and circulates to all body parts rapidly.
The disadvantages of IV administration is that once administered it can’t be recalled, rapid IV injection may produce shock condition. IV injection should be given slowly, preferably over a period of 1 min during which the blood completes its circulation. Non IV administration e.g. i.m. administration involves absorption of drug from the site of administration into systemic circulation. A drug in formulation may affect the absorption and hence bioavailability.
Certain IM preparations may release the drug slowly, e.g. Repository preparations, preparations in oil, benzathine preparations have long and sustained release because of slow partitioning. IM injection has advantage over IV injection that certain formulations that are not water soluble can not be administered easily intravenously or should be administered slowly to avoid drug precipitation. Preparations containing suspension, liposomes or nanoparticles have been developed for parenteral administration.
Preparations meant for non IV route should be non irritating, since it could damage the adjoining tissues where they are administered. Drug formulations which are irritating in nature could be administered by IV route since, the endothelium of blood vessels are less sensitive. Drugs formulated for subcutaneous administration have lesser bioavailability relative to other parenteral routes.
The absorption could be enhanced by addition of hyaluronidase or could be slowed by adding vasoconstrictor (epinephrine) or use of repository preparations. Subcutaneous implant (sterile compress pellets) are used in certain food producing animals which acts as depot for slow release of drug.
It is an aqueous or saline (occasionally oily) solution intended for parenteral administration. Such solution must be prepared from sterile, pyrogen (in simple distillation an efficient trap is used to prevent the entry of pyrogens into the condenser) free distilled water.
Some drugs are intended for topical or local therapeutic action at the site of administration. For these drugs, systemic absorption is undesirable. Drug intended for local activity generally have a direct pharmaco-dynamic action without affecting other body organs.
The dosage for a drug intended for local activity, such as topical dosage form, is expressed in concentration or as percentage of the active drug in the formulation. The drug applied is not specified because it is the concentration of the drug at the active site which relates to the pharmaco-dynamic action.
These preparations are meant for delivery of drug to the body system through skin. This route of administration releases the drug over a period of several hours without side effects. The absorption depends on dissolution and release from vehicle.
Absorption can be enhanced by suspending the drug in oily vehicle, rubbing on the skin (innunction), iontophoresis (transmission of current through the solution of the drug applied on the skin) which increases the permeability due to change in ionic concentration, phonophoresis (use of ultrasonic energy for enhancement of absorption). Incorporation of DMSO (Dimethylsulfoxide) accelerates the penetration of drug through the skin.
Various preparations meant for topical application are:
Emulsions are aqueous preparations. It is biphasic liquid dosage form of two immiscible liquids. They are made miscible by addition of a third substance (resinous or fatty substance) known as emulsifying agent (emulsifier or emergent). e.g. Emulsion of turpentine oil, castor oil.
Lotions are aqueous suspensions of insoluble material for gentle application on the skin. They are also known as ‘Washes’, e.g., White lotion, boric acid lotion.
Liniments are liquid preparations in oil, alcohol or soap solutions for external use only, applied by rubbing. Most of them are simple solutions of certain substances in alcohol or fixed oil. e.g., ammoniated liniment of camphor . Ointments: Ointments are semi-solid or solid viscous preparation. One or more active ingredients dissolved or mixed in a suitable base (fatty material) of sufficient softness intended for application on the skin by innunction (rubbing).
According to the absorption of the medicament they are classified as:
Meant for action on the epidermis
Meant for action on the layers of cutaneous tissues
Meant to penetrate deep and release medicaments in the body fluids. They may be used as protective, skin softener, parasiticide or eye ointment, e.g., sulfur, camphor, red iodide of mercury, iodine, salicylic acid, whitfield’s ointments. Formulation Ingredients affecting bioavailability – The excipients used along with drug are apparently inert, however, some ingredients may increase the solubility and thereby increases the rate of drug absorption.
Other excipients may increase the retention time of the drug in the GI tract and therefore increases the amount of drug to be absorbed, Solubility of a drug at a particular pH may be improved with the addition of an acidic or basic excipient.
Some ingredients act as carriers to increase the drug diffusion, whereas, others may retard drug dissolution and reduce drug absorption. The excipient in solid dosage forms may act as diluent, dis-integrant, lubricant, granulatory or enteric coating agent. The excipients used in liquid form act as suspending, solubilizing, preservative, sweetener, emulsion vehicle agents.