Parenteral drug delivery routes

Parenteral delivery routes are those that do not give rise to drug absorption into the splanchnic circulation. Thus, they avoid the possibility of hepatic first-pass metabolism. It should be noted that some parenteral routes do not avoid other first-pass metabolism effects (e.g., pleural metabolism for some inhaled drugs). Some major parenteral drug delivery routes are intraarterial, intrathecal, intravenous, intramuscular, trans-dermal, intranasal, buccal, inhalation, intraperitoneal, vaginal, and rectal. 

Duma RJ, Akers MJ, Turco SJ. Parenteral drug administration routes, precautions, problems, complications, and drug delivery systems. Chapter 2. In Avis KE, Lieberman HA, Lachman L, eds. Pharmaceutical Dosage Forms Parenteral Medications. 1. New York Marcel Dekker, Inc., 1992. 

Another facet of parenteral drug delivery is the implanted device, and this is perhaps the most promising and most readily commercialised area for responsive and/or active polymers. For an implanted vehicle or depot, drag release rate is controlled by dissolution and/or diffusion in the formulation, or for solid polymer implants by diffusion and/or degradation of the polymer. For more complex polymer hydrogels, the release can be controlled by the linking chemistries, and these can be made responsive to a wide variety of stimuli such as enzymatic action, redox potential and so on, as well as those noted above for the oral route. 

The term parenteral drug delivery covers a number of administration routes which have little in common other than the fact that they generally involve the use of a hypodermic needle to inject the drag into the body. This route of administration bypasses a number of physiological barriers. The constraints on the composition and formulation of the medicine are much more rigorous than for less invasive routes such as oral or transdermal delivery. Despite this, a surprising range of materials can be injected into various tissues if the appropriate precautions are taken. 

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

Parenteral administration is not perceived as a problem in the context of drugs which are administered infrequently, or as a once-off dose to a patient. However, in the case of products administered frequently/daily (e.g. insulin to diabetics), non-parenteral delivery routes would be preferred. Such routes would be more convenient, less invasive, less painful and generally would achieve better patient compliance. Alternative potential delivery routes include oral, nasal, transmucosal, transdermal or pulmonary routes. Although such routes have proven possible in the context of many drugs, routine administration of biopharmaceuticals by such means has proven to be technically challenging. Obstacles encountered include their high molecular mass, their susceptibility to enzymatic inactivation and their potential to aggregate. 

Sporadic clinical reports, without the support of data from controlled studies, repeatedly indicate the effectiveness of intratracheal administration of parenteral antimicrobial preparations in the treatment of tracheobronchitis and pneumonia in cattle. The expectation when using this route of administration is that a greater therapeutic effect will be achieved when the drug is placed as close to the infection site as possible, rather than relying on the systemic circulation for drug delivery. 

Many drugs can now be delivered rectally instead of by parenteral injection (intravenous route) or oral administration. Generally, the rectal delivery route is particularly suitable for pediatric and elderly patients who experience difficulty ingesting medication or who are unconscious. However, rectal bioavailabilities tend to be lower than the corresponding values of oral administration. The nature of the drug formulation has been shown to be an essential determinant of the rectal absorption profiles. The development of novel absorption enhancers with potential efficacy without mucosal irritation (low toxicity) is very important. The delivery of peptide and protein drugs by the rectal route is currently being explored and seems to be feasible. 

Several types of CDD systems have been designed based on various mechanisms of drug release (Table I). These mechanisms are dependent on the required site of drug delivery, the physicochemical properties of the drug and also of the delivery vehicle (13), Modes of administration can be oral, sublingual, transdermal, rectal, intrauterine, ocular, or parenteral (intramuscular, peritoneal, and subcutaneous routes of injection). 

The gastrointestinal tract is the most appropriate route for drug delivery. However, for enzymes, other proteins, and peptides, this way of administration is a new challenge for many research groups. Indeed, the parenteral route is often the preferred one for protein and peptide administration. Despite current opinion that the gut is completely impermeable to proteins and peptides, progress has recently been made in the elucidation of possible routes of penetration through the intestinal barriers. There is now evidence that small quantities of peptides and proteins can be absorbed intact from the gut. 

Methods to achieve drug targeting are introduced in Chapter 3 (Section 3.3), discussed in detail in Chapter 5 with respect to the parenteral route and also in further chapters concerning the various routes of drug delivery. 

ME systems have been attracting increasing interest as vehicles for drug delivery via the various routes. Particular emphasis has been put on the oral, transdermal, ocular, and parenteral routes. Moreover, these systems have been investigated for... 

Davis, S. S. (1982), Emulsions systems for the delivery of drugs by the parenteral route, in Bundgaard, H., Bagger Hansen, A., and Kofod, H., Eds., Optimization of Drug Delivery, Munksgaard, Copenhagen, pp. 333-346. 

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