Parenteral formulations defined

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. 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

Early studies with PDT employed complex mixtures of poorly defined porphyrins known as hemato-porphyrin derivative (photofrin I) or a partially purified mixture known as porfimer sodium (PHOTOFRIN II) that was administered parenterally with subsequent irradiation using polychromatic light sources. The major problem with this approach was the prolonged period (4-6 weeks) of photosensitivity caused by skin retention of the porphyrin formulations. This led to a search for compounds that could be administered topically and that were eliminated more readily from the skin. The porphyrin precursor S-aminolevulinic acid (ALA) is converted to various porphyrins, particularly protoporphyrin (proto), in tissues including the skin (see below). Protoporphyrin subsequently is eliminated rapidly from the body, thereby minimizing the period of skin photosensitivity to a few hours. Topically applied ALA HCl (20% wA>) and, more recently, the methyl ester of ALA have been used successfully for the PDT of various types of nonmelanoma skin cancers and premalignant lesions. 

---