Dosage forms parenteral administration

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. 

Duma, R. J., Akers, M. J., and Turco, S. Parenteral drug administration routes, precautions, problems, and complications. In Pharmaceutical Dosage Forms Parenteral Medications, 2nd ed. (K. E. Avis, L. Lachman, and H. Lieberman, Eds.). Marcel Dekker, New York, 1991. 

The appropriate type of parenteral dosage form and administration site has to meet the medical needs of the patient. Criteria that have to be considered are onset and duration of pharmacological activity, site of therapeutic action, the volume to be administered, inpatient or outpatient. 

In the request for a pharmacy preparation, the physician often prescribes the administration route. Pharmacists have to critically evaluate whether the proposed route is appropriate to reach the desired bioavailability. For example, conventional oral medications may not be suitable for patients with a nasogastric feeding tube, children, or nauseous patients and alternative routes such as parenteral, rectal, or nasal have to be considered (see also Sect. 37.6.3). When adapting a dosage form or administration route to special needs of a patient, the pharmacist is required to consider safety aspects. It is important to recognise that an active substance approved for oral administration may never have... 

The pharmaceutical industry directs considerable effort toward maximizing the usefulness and reliability of oral dosage forms in an effort to minimize the need for parenteral administration. Factors that... 

In recent years, parenteral dosage forms, especially IV forms, have enjoyed increased use. The reasons for this growth are many and varied, but they can be summed up as (a) new and better parenteral administration techniques, (b) an increasing number of drugs that can be administered only by a parenteral route, (c) the need for simultaneous administration of multiple drugs in hospitalized patients receiving IV therapy, (d) new forms of nutritional therapy, such as intravenous lipids, amino acids, and trace metals, and (e) the extension of parenteral therapy into the home. 

In-depth discussions of the anatomy of the eye and adnexa have been adequately covered elsewhere in the pharmaceutical literature [13-17] and in recent texts on ocular anatomy. Here a brief overview is presented of the critical anatomical features that influence the nature and administration of ophthalmic preparations. In this discussion, consideration will be given primarily to drugs applied topically, that is, onto the cornea or conjunctiva or into the palpebral fornices. Increasingly, drugs are being developed for administration by parenteral-type dosage forms subconjunctivally, into the anterior and posterior chambers, the vitreous chamber, Tenon s capsule, or by retrobulbar injection. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

Parenteral Dosage Forms and Invasive Devices. Parenteral and invasive devices provide the distinct advantage of the delivery of medication directly into the bloodstream or at the site of action. Additionally, these methods result in assures patient compliance because, in most cases, an individual other than the patient is responsible for the administration of medication by these means. Unfortunately, this attribute is counteracted by numerous problems that are illustrated in Table 11. 

The present chapter deals with calculations involving isotonicity, pH, and buffering of topical preparations. The discussion presented here is also relevant to the dosage forms for other routes of administration including parenteral routes. 

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). 

Judicious selection of excipients for parenteral dosage forms is critical due to their systemic administration.106107 Excipients of a parenteral dosage form may have a significant effect on product safety including injection site irritation or pain. Permissible excipients for parenteral dosage forms are far less than those for oral dosage forms. 

One of the main disadvantages of depot parenteral preparations is that administration of these preparations may not be acceptable to the patient. The depot preparation requires a lower dosing frequency when compared with other dosage forms. 

Dosage form Enbrel is supplied as a sterile, lyophilized powder for parenteral administration after reconstitution with sterile bacteriostatic water for injection. Each single-use vial of Enbrel contains etanercept 25 mg. 

Suppositories are pharmaceutical dosage forms intended for administration of medicine via the rectum, vagina, or urethra that melt, soften, or dissolve in the body cavity. Rectal and vaginal suppositories are most common but urethral suppositories are sometimes used. Suppositories are indicated for administering drugs to infants and small children, severely debilitated patients, those who cannot take medications orally, and those for whom the parenteral route might be unsuitable. Suppositories are used to administer drugs for either systemic or local application. Local applications include the... 

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. 

Parenteral Dosage Forms. The most commonly used forms for drug products designed and manufactured for injection through the skin include those meant for subcutaneous, intramuscular, and intravenous administration. 

As discussed above, cosolvents can be an effective way to alter the solubility and stability of compounds. In formulating a parenteral product, often these two parameters can be exploited to produce a commercially acceptable, elegant product. Often cosolvents can be used to concentrate a formulation to allow production of a dosage form for presentation as an ampule or vial. The concentrated ampule or vial is then diluted before administration to the patient. Nema et al. [107] has reviewed excipient use, including cosolvents, in commercially available injectable products. 

Allemann, E., J. C. Leroux, and R. Gurny. 1998. Biodegradable nanoparticles of poly(lactic acid) and poly(lactic-c-glycolic acid) for parenteral administration. Pharmaceutical Dosage Forms Disperse Systems, H. Lieberman, M. Rieger, G. Banker (Eds.), Vol. 3, New York, Marcel Dekker. pp. 163-193. 

Dissolution rate improvement may be beneLcial for producing readily dissolved solids for parenteral or oral administration of drugs subject to hydrolysis. For solid oral dosage forms, the initial rate increase can be sufLcientto alterthe amount of drug that enters the blood and improve the there peutic potency. Unlikan vitro test systems, the concentration in the Gl cavity may never approach... 

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