Parenteral formulation

Opioidergic agents. Naltrexone and nalmefene, opioid antagonists with no intrinsic agonist properties, have been studied for the treatment of alcohol dependence. Naltrexone has been studied much more extensively than nalmefene for this indication. In 1984 naltrexone was approved by the FDA for the treatment of opioid dependence, and in 1994 it was approved for the treatment of alcohol dependence. Nalmefene is approved in the United States as a parenteral formulation for the acute reversal of opioid effects (e.g., after opioid overdose or analgesia). 

The antibiotic is administered orally as the palmitate, which is tasteless this is hydrolysed to chloramphenicol in the gastrointestinal tract. The highly water-soluble chloramphenicol sodium succinate is used in the parenteral formulation, and thus acts as a pro-drug. 

Parenteral Formulations Iron dextran InFED 50 mg/tablet 50 mg/mL... 

Emulsifiers. Natural lecithin is one of the most widely used emulsifiers because it is metabolized in the body. However, type I allergic reaction to soybean lecithin emulsified in lipid solutions has been observed [195], Among the synthetic emulsifying agents, block copolymers of polyoxyethylene-polyoxypropylene (poloxamer) have attracted increasing interest for parenteral emulsions. Other examples of emulsifiers commonly found in parenteral formulations are given in Table 9 [190]. 

Due to particle sizes in the micrometer range, parenteral suspensions are generally limited to either subcutaneous or intramuscular routes of administration. However, ultrafine suspensions can be approached by high-pressure homogenization [200]. The particle size obtained from this technique is in the 100 500 nm range, thus intravenous administration is possible [201]. General information on parenteral formulations is given in Chapter 12. 

Studies of polymorphs in recent years have pointed out the effects of polymorphism on solubility and, more specifically, on dissolution rates. The aspect of polymorphism that is of particular concern to the parenteral formulator is physical stability of the product [8]. Substances that form polymorphs must be evaluated so that the form used is stable in a particular solvent system. Physical stresses that occur during suspension manufacture may also give rise to changes in crystal form [9]. 

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). 

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. 

Y. J. Wang and M. A. Hanson, Parenteral formulations of proteins and peptides Stability and stabilizers. 

Etomidate is an imidazole derivative similar to ketoconazole that inhibits 11-hydroxylase. Because it is only available in a parenteral formulation, its use is limited to patients with acute hypercortisolemia awaiting surgery. 

Parasitic pressure drops, 15 823t, 824 Para- substituents, 9 371, 372 Paratacamite, 7 769 Parathion, 13 524-525 Paratungstates, 25 383 demand for, 24 276 Parcel charter, 25 330 Parenteral drug dosage forms, IS 713-716 Parenteral drug injections, prolonged action, 18 715-716 Parenteral formulations,... 

Benzoic acids substituted with a basic side chain also are also of interest as pro-moieties whose physicochemical properties and rates of enzymatic hydrolysis can readily be modulated. A number of drugs have been converted to prodrugs with this type of pro-moiety, e.g., hydrocortisone, prednisolone, acyclovir, chloramphenicol, and paracetamol [148] [149], These prodrugs appear well suited as parenteral formulations, being water-soluble, stable in slightly acidic solution, and readily hydrolyzed enzymatically. As examples, we consider here the hydrolysis in human plasma of a number of (aminomethyl)ben-zoates of metronidazole (8.109-8.115, Sect. 8.5.5.1, Table 8.9) [138], These prodrugs are very rapidly activated, which may be beneficial for parenteral administration. However, this type of pro-moiety may be cleaved too rapidly after oral administration to be of interest for poorly absorbed drugs. 

Gupta, P.K., Patel, J.P., and Hahn, K.R., Evaluation of pain and irritation following local administration of parenteral formulations using the rat paw lick model, /. Pharm. Sci. Technol., 48, 159, 1994. 

Strickley, R.J., Parenteral formulation of small molecules therapeutics marketed in the United States-Part III, PDA. Pharm. Sci. Tech., 54, 152, 2000. 

The antimykotie amphotericine is eneapsulated in liposomes and marketed as Am-Bisome" against severe systemic mycosis. The liposomal encapsulation reduces the toxicity of amphotericine while increasing the half-life of the drug and plasma level peaks [31], For stability reasons, the parenteral formulation is a lyophilized powder whieh has to be reeonstituted by adding the solvent just before administration. 

Dextrose is widely used as an isotonic media in parenteral formulations. Sterilisation using autoclaving has been reported to induce the formation of fructose via an isomerisation reaction, with the resultant formation of 5-hydroxymethyl-furfural [90]. 

BMS-204352, a novel substituted 3-fluorooxindole, is a potassium channel opener being developed for the treatment of stroke. Nassar et al. [96] reported on the development of a non-aqueous parenteral formulation of BMS-204352. This formulation was composed of a mixture of PEG 300, polysorbate 80, ethanol and water. The authors reported on the formation of 1-hydroxymethyl adduct of BMS-204352 (formaldehyde adduct), which was linked with residual levels of formaldehyde in the polymeric excipients. 

High potency (HP) injection - HP injection is a highly concentrated solution of hydromorphone intended for use in opioid-tolerant patients. Do not confuse HP injection with standard parenteral formulations of injection or other opioids. Overdose and death could result. 

Folic acid is used for the treatment of folate deficiency. Oral folic acid is usually the therapy of choice. For megaloblastic anemia doses of 5 mg daily for 4 months should be effective. Folinic acid is available in a parenteral formulation which may be indicated when oral therapy is not feasible and for rescue treatments following certain anti-cancer regimens. 

Betamethasone is hardly ever used orally. It has a long duration of activity and can therefore also be used for alternate-day therapy. The parenteral formulation is also the sodium phosphate salt which when given IV or IM has a rapid onset of action. There are many similarities with dexamethasone such as their metabolic pathways and the indications for which both steroids are used, like the prevention of neonatal RDS and reduction of raised intracranial pressure. Combinations of betamethasone acetate and sodium phosphate have, when used for intra-articular and intra-lesional injections, the dual advantage of a rapid onset of action together with the long duration of action of a depot preparation. 

Lungs Asthma Do not use NSAIDs in patients with ASA hypersensitivity or pronounced aUergic asthma. Do not use parenteral formulations in asthmatics... 

Morphine 3 12-20 Basehne drug. The dose is adjusted when changing from parenteral formulation to oral, with a 3-fold increase due to low bioavaUabUity. The amount needed shows large variations between individuals. Particular sensitivity in the elderly and in patients with kidney disease. Risk of abuse... 

Differential pulse polarography has been used for the estimation of progesterone, testosterone, and related 4-en-3-ones in some parenteral formulations (in oil or aqueous suspensions). ... 

Parenteral formulation available as orphan drug and in Canada Patient/Family Education... 

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