Formulation intramuscular injection

Loomis, E.C. and R.C. Schock. 1978. Comparison of famphur (Warbex) pour-on and intramuscular injectable formulations for cattle grub control, California, 1975-1976. Jour. Med. Entomol. 14 649-651. 

Reports of adverse reactions to povidone primarily concern the formation of subcutaneous granulomas at the injection site of intramuscular injections formulated with povidone. Evidence also exists that povidone may accumulate in the organs of the body following intramuscular injection. ... 

Depot injection A long-acting formulation of an antipsychotic drug given by occasional (often monthly) intramuscular injection. 

DMPA 150 mg administered by deep intramuscular injection in the gluteal or deltoid muscle within 5 days of the onset of menstrual bleeding inhibits ovulation for more than 3 months, and the dose should be repeated every 12 weeks to ensure continuous contraception. A new formulation contains 104 mg of DMPA (Depo-SubQ Provera 104), which is injected subcutaneously into the thigh or abdomen. The manufacturer recommends excluding pregnancy in women more than 1 week late for repeat injection of the intramuscular formulation or 2 weeks late for repeat injection of the subcutaneous formulation. 

An intramuscular injection form of olanzapine, administered at doses from 2.5 to 10 mg, is now available for the management of acute agitation in the inpatient setting. This injectable olanzapine has no role in outpatient care however, a depot formulation of olanzapine is expected in the near future. 

Mesterolone is a non-17-alkylated derivative which is also has weak activity orally. Testosterone itself has little activity when taken orally and is used sublingually or as an implant. By esterification of testosterone formulations of long-acting testosterone derivatives in oily solutions for intramuscular injection were developed. 

Absorption of phenytoin is highly dependent on the formulation of the dosage form. Particle size and pharmaceutical additives affect both the rate and the extent of absorption. Absorption of phenytoin sodium from the gastrointestinal tract is nearly complete in most patients, although the time to peak may range from 3 to 12 hours. Absorption after intramuscular injection is unpredictable, and some drug precipitation in the muscle occurs this route of administration is not recommended for phenytoin. In contrast, fosphenytoin, a more soluble phosphate prodrug of phenytoin, is well absorbed after intramuscular administration. 

Benzathine and procaine penicillins are formulated to delay absorption, resulting in prolonged blood and tissue concentrations. A single intramuscular injection of 1.2 million units of benzathine penicillin maintains serum levels above 0.02 mcg/mL for 10 days, sufficient to treat B-hemolytic streptococcal infection. After 3 weeks, levels still exceed 0.003 mcg/mL, which is enough to prevent B-hemolytic streptococcal infection. A 600,000 unit dose of procaine penicillin yields peak concentrations of 1-2 mcg/mL and clinically useful concentrations for 12-24 hours after a single intramuscular injection. 

The clinical usefulness of somatostatin is limited by its short half-life in the circulation (3 minutes) when it is administered by intravenous injection. Octreotide is a synthetic octapeptide with actions similar to somatostatin. When administered intravenously, it has a serum half-life of 1.5 hours. It also may be administered by subcutaneous injection, resulting in a 6- to 12-hour duration of action. A longer-acting formulation is available for once-monthly depot intramuscular injection. 

Although it is not a major elimination route following intravenous or intramuscular injection of penicillin G to dairy cattle, milk constitutes a very important route of elimination following intramammary injection since most of the dose enters milk (58, 59). The persistence of residues in milk does depend on the formulation and route of administration, but, in a wide variety of trials, residues were not found to persist beyond 5 days after the end of treatment (59, 60). Transfer of penicillin G from treated to untreated quarters has also been observed... 

Following intramuscular injection of a long-acting oxytetracycline formulation, all sheep tissue residues were below the US tolerance of 0.1 ppm by 14 days after treatment (235). After intramuscular administration to a dairy cow of a single dose of 5 mg oxytetracycline/kg bw, residues were present in milk for as long as 4 days after dosing at concentrations ranging from 370 ppb at day 1 posttreatment to 10 ppb at day 4 posttreatment (233). 

The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle (52). Chloramphenicol, tylosin, penicillins, dihydrostreptomycin, and oxytetracycline have been shown to produce local irritation at the site of injection, leading to residue persistence this may be exacerbated by the solvent used. However, residues do not persist with proper injection of drugs and use of formulations that do not cause severe irritation (52), as has been demonstrated with one oxytetracycline product that produced little irritation (53-55). 

Clinical use Etofenamate (Coletta et al., 1988) is a nonsteroidal anti-inflammatory drug which is used for the treatment of joint, musculoskeletal and soft tissue disorders. Etofenamate is used mainly as a topical formulation (500-1300 mg/day) and is also available for intramuscular injection (1 g/day). 

By increasing the hydrophobicity of plasmids and reducing their net negative surface charge, PVP may facilitate the uptake of plasmids by muscle cells. Intramuscular injection of PVP-based plasmid formulations in rats significantly increased the number and distribution of expressing cells, as compared to unformulated plasmid. The formation of condensed interpolyelectrolyte complexes between PVP and DNA has been proposed to both protect DNA from nuclease degradation and facilitate its cellular uptake by hydrophobic interaction with cell membranes. The increased hydrophobicity of the complex may enhance interaction with cell membranes and facilitate cell uptake. 

The neuroleptics show variable absorption after oral administration. These agents readily pass into the brain, have a large volume of distribution, bind well to plasma proteins, and are metabolized to many different substances by the P-450 system in the liver. Fluphenazine decanoate and haloperidol decanoate are slow release (up to 3 weeks) formulations of neuroleptics, administered by intramuscular injection. These drugs are increasingly used in treating outpatients and individuals who are noncompliant. However, about 30% of these patients develop extrapyramidal symptoms. The neuroleptic drugs produce some tolerance but little physical dependence. 

The most important action is to ensure that the client receives appropriate pharmacological treatment. One of the main problems in schizophrenia is lack of medication compliance. This is often caused by lack of client collaboration, often explained by the intrinsic pathological characteristics of the disease itself. Both typical and atypical depot antipsychotics formulations are available. Depot preparations are typically administered by intramuscular injection every 1-4 weeks. This may be of great advantage in patients with poor compliance. 

Therapeutic formulations contain a recombinant form of IFN-a (either interferon alfa-2a or interferon alfa-2b). These are available as powders for reconstitution or as prefilled injection pens. The drug is administered by subcutaneous injection (or intravenous for reconstituted powder formulations) and intramuscular injection. The dosage is usually stated as units per millilitre (refer to BNF for various preparations and dosages). Powder formulations of interferon alfa-2b also contain glycine, sodium phosphate (mono- and dibasic) and human albumin prefilled pens contain sodium chloride, edetate disodium, polysorbate 80 and m-cresol as a preservative. 

---