Parenteral dosage form

The USP recognizes three forms of water for parenteral dosage forms. Water for injection is prepared by reverse osmosis or distillation, which... 

It is generally assumed that adequate vitamin levels in humans can be obtained through a balanced diet. However, ongoing studies continue to indicate that the majority of the U.S. population is not receiving even the RDA through diet. Supplementary vitamins are thus provided for fortification of foods (20) and as oral or parenteral dosage forms. 

In the human market, oral and parenteral dosage forms are prepared from the crystal. However, because of the extremely high potency, more dilute (0.1—10%) forms are avabable. These include dilutions with mannitol, triturations on dicalcium phosphate or resins, and spray-dried forms. Prices for these forms are driven by that of the crystal, which in early 1996 was ca 9.50/gram (95). Prices for the vitamin have risen during the first half of the 1990s. However, Htde growth in price beyond inflation is anticipated. 

P2-Agonists cause airway smooth muscle relaxation by stimulating adenyl cyclase to increase the formation of cyclic adenosine monophosphate (cAMP). Other non-bronchodilator effects have been observed, such as improvement in mucociliary transport, but their significance is uncertain.11 P2-Agonists are available in inhalation, oral, and parenteral dosage forms the inhalation route is preferred because of fewer adverse effects. 

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. 

One of the most difficult parenteral dosage forms to formulate is a suspension. It requires a delicate balance of variables to formulate a product that is easily resuspended and can be ejected through an 18-to 21-gauge needle through its shelf life. To achieve these properties it is necessary to select and carefully maintain particle size distribution, zeta potential, and rheological properties, as well as the manufacturing steps that control wettability and surface tension. The requirements for, limitations in, and differences between the design of injectable suspensions and other suspensions have been previously summarized [17b, 18,19]. 

A summary of sustained- and controlled-release parenteral dosage forms is included in Chapter 15. This subject is also covered extensively by Chien [34],... 

K. S. Lin, J. Anschel, and C. J. Swartz, Parenteral formulations IY solubility considerations in developing a parenteral dosage form, Bull. Parenter. Drug Assoc., 25, 40-50 (1971). 

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. 

Development of Biopharmaceutical Parenteral Dosage Forms, edited by John A. Bontempo... 

Vries et al. [3.59] described the development of a stable parenteral dosage form of the cytotoxic drug E 09. E 09 dissolves poorly in water and its solution is unstable. With the addition of 200 mg of lactose per vial containing 8 mg of E 09, an optimum formulation was developed with respect to solubility, dosage of E 09 and length of the freeze drying cycle. DSC studies have been used to select the most effective parameters. The freeze dried product remains stable for 1 year when stored at 4 °C in a dark environment. 

Ikeda, M. Development of a multilayer lyophilization technique for parenteral dosage forms. PDA Asian Symposium, p. 261-266, Tokyo, 1994... 

The preparation of parenteral dosage forms of approved and potential drugs for animals is the same as for humans. Turco and King (1974) provide a comprehensive review of the subject, which, though written with human therapeutics in mind, contains very little that is not applicable to animals. Sterility, lack of pyrogenicity, blood compatibility, and low to no irritation at the point of injection are biological requirements there are also a corresponding set of physicochemical requirements. 

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. 

Broadhead, J., Parenteral dosage forms, in Pharmaceutical Preformulation and Formulation, Gibson, M., Ed., Interpharm/CRC Press, New York, 2004. 

Trihexyphenidyl and biperiden have strong central and peripheral anticholinergic activity and both idiopathic as well as drug-induced Parkinsonism can be an indication for their use. Especially the tremor of Parkinsonism is favorably influenced. Large doses of trihexyphenidyl are said to have a mood modifying effect. The existence of a parenteral dosage forms of biperiden extends the applications of this agent. Both have a duration of action of 6-12 hours. 

Nema S, Brendel RJ, Washkuln RJ. Excipients—their role in parenteral dosage forms. In Swarbrick J, Boylan JC, eds. Encyclopedia of Pharmaceutical Technology. 2nd ed. New York Marcel Dekker, Inc., 2002 1164. 

Another important component of most vaccine formulations is a suitable preservative. The three most commonly used preservatives in available vaccines are phenol, 2-phenoxyethanol, and ethyl mercurithiosalicylate (thimerosal). Thimerosal, in particular, is used in multidose vials as an antimicrobial preservative. Concerns about the presence of mercury in thimerosal (25 pg/dose) has led to FDA stopping the use of this preservative in all vaccines by an amendment to the FDA Modernization Act of 1997. By 2001, thimerosal was removed from most childhood vaccines as a precautionary measure. The sources of all of the preservatives for vaccines are the same suppliers that supply preservatives for the parenteral dosage forms (J. T. Baker, Aldrich, Spectrum, etc. from U.S.A.). Table 2 lists some of the preservative concentrations in common vaccines. 

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. 

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