Parenteral delivery routes intramuscular administration

The success of vaccination depends primarily on the method of presenting the antigen to the host immune system. Antigens have usually been delivered by parenteral (such as intravenous, intramuscular, intraperito-neal, intradermal, and subcutaneous) administration, but recent studies have shown that other routes of delivery such as intranasal, oral, and transdermal delivery have also been effective. In some cases, vaccination through mucosal routes resulted in better responses in IgA production. Because non-parenteral vaccine delivery presents many obvious advantages, numerous attempts have been made on the development of non-parenteral delivery of vaccines. 

Parenteral is defined as situated or occurring outside the intestine, and especially introduced otherwise than by way of the intestines —pertaining to essentially any administration route other than enteral. This field is obviously too broad for an adequate focus in one book, let alone one chapter. Many have nonetheless used the term synonymously with injectable drug delivery. We restrict ourselves to this latter usage. This would thus include intravenous, intramuscular, subcutaneous, intrathecal, and subdural injection. In this chapter we discuss the theoretical and practical aspects of solubilizing small molecules for injectable formulation development and will examine the role of surfactants and other excipients in more recent parenteral delivery systems such as liposomes, solid-drug nanoparticles and particulate carriers. 

The most important requirement is that the salt possesses sufficient solubility at physiologically compatible pH values to permit incorporation into the dosage form. Buffering the solution to an appropriate pH can often enhance solubility. Salts may also be prepared in situ in the formulation. This is particularly useful when the main route of administration utilizes the parent drug form. Where the aqueous solubility of the salt is not sufficiently high, co-solvents may need to be added to enhance solubility (e.g. propylene glycol is used as the vehicle in phe-nobarbitone sodium injection). Parenteral solutions based on co-solvent vehicles normally cannot be directly injected intravenously because there is the risk of precipitation at the injection site. Therefore, such products are diluted with isotonic saline or 5%w/v dextrose solution to produce a lower concentration that remains soluble and can be safely administered by infusion. Alternative delivery routes are by subcutaneous or intramuscular administration by which, in... 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Parenteral (injected) administration of drugs provides a solution to many problems associated with the oral delivery route. A drug injected into the blood circulation is considered to be completely bioavail-able thaefore, the quantity of the surfactants and otha inactive excipients in intravenous dosage forms are usually strictly limited. The most common alternative routes of parenteral drug administration are intramuscular or subcutaneous injections [2], Several otha injection routes are available to elicit rapid local reaction, such as intrathecal, intraarticular, and intracardiac. 

Multiple emulsions have been widely studied as means of delivering drugs via oral, topical, and parenteral routes. The applications include protein delivery (Cournarie et al., 2004), delivery of antibiotics to the vagina (Tedajo et al., 2005), sustained delivery (Vaziri and Warburton, 1994), and vaccine delivery (Bozkir and Hayta, 2004). The immunological response to a vaccine also depends on the route of administration. Most current vaccines are administered intramuscularly, which induces immunization as a systemic immunity. However, the live polio vaccine and the live typhoid vaccine are administered orally. Local immunization (oral, intranasal, or intravagina) may be preferred, since mucosal surfaces are the common entrance to many pathogens. Moreover local immunization induces both mucosal and systemic immunity. Ease of administration and avoidance of systemic side effects are additional advantages of local immunization (Walker, 1994 Shalaby, 1995). Nevertheless, successful local immunization has only been achieved with a limited number of oral vaccines. Also there are very few studies on multiple emulsions used in the immunization process, especially on parenteral and oral administration. 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

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). 

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