Parenteral Drug Delivery System PDF

Parenteral Drug Delivery Parenteral literally means introduction of substances into the body by routes other than the gastrointestinal tract, but practically the term is applied to injection of substances by subcutaneous, intramuscular, intravenous, and intra-arterial routes. Injections made into s...

Parenteral Drug Delivery Parenteral literally means introduction of substances into the body by routes other than the gastrointestinal tract, but practically the term is applied to injection of substances by subcutaneous, intramuscular, intravenous, and intra-arterial routes. Injections made into specific organs of the body for targeted drug delivery will be described under various therapeutic areas. Parenteral administration of the drugs is now an established part of medical practice and is the most commonly used invasive method of drug delivery. Many important drugs are available only in parenteral form. Conventional syringes with needles are either glass or plastic (disposable). Nonreusable syringe and needle come either with autodestruct syringes which lock after injection or retractable needles. Advantages of parenteral administration are: Rapid onset of action Predictable and almost complete bioavailability Avoidance of the gastrointestinal tract with problems of oral drug administration Provides a reliable route for drug administration in very ill and comatose patients, who are not able to ingest anything orally Major drawbacks of parenteral administration are: Injection is not an ideal method of delivery because of pain involved and patient compliance becomes a major problem. Injections have limitations for the delivery of protein products particularly those that require sustained levels. Comments on various types of injections are given in the following text.  Subcutaneous: This involves the introduction of the drug to a layer to subcutaneous fatty tissue by the use of a hypodermic needle. Large portions of the body are available for subcutaneous injection which can be given by the patients themselves as in the case of insulin for diabetes. Various factors which influence drug delivery by subcutaneous route are: Size of the molecules as the larger molecules have slower penetration rates than smaller ones. Viscosity may impede the diffusion of drugs into body fluids. The anatomical characteristics of the site of injection such as vascularity and amount of fatty tissue influence the rate of absorption of the drug. Subcutaneous injections usually have a lower rate of absorption and slower onset of action than intramuscular or intravenous injections. The rate of absorption may be enhanced by infiltration with the enzyme hyaluronidase. Disadvantages of subcutaneous injection are: The rate of absorption is difficult to control from the subcutaneous deposit. Local complications which include irritation and pain at site of injection. Injection sites have to be changed frequently to avoid accumulation of the unabsorbed drug which may cause tissue damage. Several self-administration subcutaneous injection systems are available and include conventional syringes, pre-filled glass syringes, autoinjectors, pen pumps and needle-less injectors. Subcutaneous still remains predictable and controllable route of delivery for peptides and macromolecules. Intramuscular Injections : These are given deep into skeletal muscles, usually the deltoids or the gluteal muscles. The onset of action after intramuscular injection is faster than with subcutaneous injection but slower than with intravenous injection. The absorption of the drug is diffusion controlled, but it is faster due to high vascularity of the muscle tissue. The rate of absorption varies according to physicochemical properties of the solution-injected and physiological variables such as blood circulation of the muscle and the state of muscular activity. Disadvantages of intramuscular route for drug delivery are: Pain at the injection site. Limitation of the amount injected according to the mass of the muscle available. Degradation of peptides at the site of injection. Complications include peripheral nerve injury and formation of hematoma and abscess at the site of injection. Inadvertent puncture of a blood vessel during injection may introduce the drug directly into the blood circulation. Most injectable products can be given intramuscularly. Numerous dosage forms are available for this route: oil-in-water emulsions, colloidal suspensions, and reconstituted powders. The product form in which the drug is not fully dissolved generally results in slower, more gradual absorption and slower onset of action with longer-lasting effects. Intramuscularly administered drugs typically form a depot in the muscle mass from which the drug is slowly absorbed. Peak drug concentrations are usually seen from 1 to 2 h. Factors which affect the rate of release of the drug from such a depot include: Compactness of the depot as the release is faster from a less compact and more diffuse depot Concentration and particle size of drug in the vehicle Nature of solvent in the injection Physical form of the product The flow characteristics of the product Volume of the injection  Intravenous Administration : This involves injection in the form of an aqueous into a superficial vein or continuous infusion via a needle or a catheter placed in a superficial or deep vein. This is the only method of administration available for some drugs and is chosen in emergency situations because the onset of action is rapid following the injection. Theoretically, none of the drug is lost; smaller doses are required than with other routes of administration. The rate of infusion can be controlled for prolonged and continuous administration. Devices are available for timed administration of intermittent doses via an intravenous catheter. The particles in the intravenous solution are distributed to various organs depending on the particle size. Particles larger than 7 μm are trapped in the lungs, and those smaller than 0.1 μm accumulate in the bone marrow. Those with diameter between 0.1 and 7 μm are taken up by the liver and the spleen. This information is useful in targeting of a drug to various organs. Disadvantages of the intravenous route are: Immune reactions may occur following injections of proteins and peptides. Trauma to veins can lead to thrombophlebitis. Extravasation of the drug solution into the extravascular space may lead to irritation and tissue necrosis. Infections may occur at the site of catheter introduction. Air embolism may occur due to air sucked in via the intravenous line. It is now possible to modify the kinetics of disposition and sometimes the metabolic profile of a drug given by intravenous route. This can be achieved by incorporating the drug into nanovesicles such as liposomes.  Intra-arterial: Direct injection into the arteries is not a usual route for therapeutic drug administration. Arterial puncture and injection of contrast material has been carried out for angiography. Most of the intra-arterial injections or arterial perfusions via catheters placed in arteries are for regional chemotherapy of some organs and limbs. Intra-arterial chemotherapy has been used for malignant tumors of the brain.