Formulation subcutaneous injection

Not commercially available in the United States as a sublingual formulation only available in United States as subcutaneous injection that is FDA approved for Parkinson s disease. 

No antibody activity was found after oral immunization in any of the individual rabbits immunized with liposphere R32NS 1-vaccine formulation. However, rabbit immunization by all parenteral routes tested resulted in enhanced immunogenicity, with increased antibody IgG levels over the entire postimmunization period. The individual rabbit immune response shows that immunization by subcutaneous injection was the most effective vaccination route among all parenteral routes of administration tested. 

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). 

Systemic absorption of pulmonary-deUvered peptides and proteins has been the objective of many investigations [2]. The most successful work in this field is the development of insulin formulations for inhalation.These dosage forms might, in the near future, become a suitable alternative for the current subcutaneous injection of insulin that is used to obtain meal-time glucose control [3]. In spite of the strict requirements regarding dose variability for insulin, the pulmonary products under development seem to be as safe as the subcutaneous injections. 

Some of the dosage formulations available for protein pharmaceuticals are listed in Table 5.7. An examination of Table 5.7 reveals that no protein drug up until this time has been formulated for oral administration. Most protein drugs are administered by means of injection (parenteral administration). Parenteral administration includes intravenous, intra-arterial, intracardiac, intraspinal or intrathecal, intramuscular, intrasynovial, intracuta-neous or intradermal, subcutaneous injections, and injection directly into a dermal lesion (e.g., a wart). The parenteral route of administration requires a much higher standard of purity and sterility than oral administration. It also may require trained... 

Route of administration Humulin 50/50, Humulin 70/30, Humulin L, Humulin N, Humulin R, Humulin R (U-500), and Humulin U are for subcutaneous injection only. The same applies to formulations containing Novolin. Velosulin BR is indicated... 

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. 

Tramadol is available as drops, capsules, and sustained-release formulations for oral use, suppositories for rectal use, and solution for intramuscular, intravenous, and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 h, reach peak concentrations after 4.9 h, and have a bioavailability of 87 to 95% compared with capsules. One 100-mg dose given to healthy volunteers resulted in plasma levels of 375 ng/ml at 1.5 h.55 Tramadol is 20% bound to plasma protein and it is rapidly distributed in the body it is mainly metabolized by O- and A-demethylation forming glucuronides and sulfates that are excreted by the kidney. 

Insulin has a half-life of only a few minutes when injected intravenously. It is therefore prepared in different formulations for subcutaneous injection, with different half-lives of absorption, giving different durations of action. The main formulations, with their approximate durations of action are given in Table 2. 

Intravenous injection is the most common route although subcutaneous injection may also be used. A concentrated nasal spray formulation has been proved to be efficient for home treatment of patients with bleeding episodes or even minor surgical procedures and has also been used prophylacticly (4). The nasal spray used to treat diabetes insipidus (Desmospray) is too dilute for use in disorders of hemostasis. Similarly, desmopressin in tablet form (Desmotabs) is intended for treatment of nocturnal enuresis in children and is of no use in the treatment of hemostatic disorders. 

Since its discovery, isolation, and purification in the early twentieth century, insulin has been administered to diabetic patients exclusively by injection until the recent introduction of inhaled insulin. Insulin possesses certain physiochemical properties that contribute to its limited absorption from the gastrointestinal tract, and requires subcutaneous injection to achieve clinically relevant bioavailability. With a molecular size of 5.7 kDa, insulin is a moderately sized polypeptide composed of two distinct peptide chains designated the A chain (21 amino acid residues) and the B chain (30 amino acid residues) and joined by two disulfide bonds. Like all polypeptides, insulin is a charged molecule that cannot easily penetrate the phospholipid membrane of the epithelial cells that line the nasal cavity. Furthermore, insulin monomers self-associate into hexameric units with a molecular mass greater than 30 kDa, which can further limit its passive absorption. Despite these constraints, successful delivery of insulin via the nasal route has been reported in humans and animals when an absorption enhancer was added to the formulation. 

Several peptide products used in the treatment of diabetes mellitus, in addition to insulin, are currently administered by subcutaneous injection and these drugs are candidates for development of nasal formulations. Glucagon-like peptide-1 (GLP-l)-related peptides stimulate the insulin response to glucose and diminish the release of glucagon after a meal. These effects diminish the excessive postprandial increase in glucose observed after a meal in persons with type 2 diabetes mellitus. GLP-1-related peptides must be administered by subcutaneous injection before meals in order to be effective. This requirement for injection before each meal is likely to impact the utilization of these products by persons with type 2 diabetes. Exendin-4 is a GLP-1-related peptide with a molecular mass of 4.2 kDa. The development of a GLP-1-related peptide nasal formulation containing an absorption enhancer would allow patients to scll-administer one of these drugs just before a meal without the need for a subcutaneous injection. 

Leptin is a peptide hormone secreted by adipocytes. Recombinant human leptin has been investigated for its potential as an antiobesity agent [105,106]. Women with hypothalamic amenorrhea display reduced levels of leptin. Leptin administration to these women improves reproductive and neuroendocrine function [107], Nasal administration of leptin to rats in the presence of either TDM (1) or LPC [108] caused a significant increase in serum leptin levels. Increased serum leptin levels were associated with reduced food consumption [108], The development of an effective nasal formulation of leptin containing an absorption enhancer may allow more frequent dosing with leptin and thereby overcome the limited efficacy observed following subcutaneous injections of large doses of this hormone. 

To facilitate multiple subcutaneous injections of insulin, particularly during intensive insulin therapy, portable pen-sized injectors have been developed. These contain cartridges of insulin and replaceable needles. Disposable insulin pens are also available for selected formulations. These include regular insulin, insulin lispro, insulin aspart, NPH insulin, and premixed 70%/30% and 50%/50% NPH/regular, 75% NPL/25% lispro, 50% NPL/50% lispro, and 70% NPA/30% aspart insulin. They have been well accepted by patients because they eliminate the need to carry syringes and bottles of insulin to the workplace and while traveling. 

An initial burst release of leuprolide from the microsphere depot occurs in vivo, followed by quasi-linear release for the rest of the time period. The efficacy of leuprolide depot formulations was found to be the same as the efficacy achieved with daily subcutaneous injections of 1 mg leuprolide formulation. 

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. 

There has been a report on chitosan utility in improving the intranasal absorption of high-molecular-weight (>10-kDa) therapeutic protein. Chitosan glutamate powder blend or granules with recombinant hGH have been evaluated for intranasal administration in sheep. Relative to subcutaneous injection the nasal formulations produced bioavailabilities of 14 and 15%, respectively [77],... 

Subcutaneous injection (SC) Prompt from aqueous solution Slow absorption from repository formulations Generally, used for insulin injection Rate of drug absorption depends upon blood flow and injection volume... 

Models that do assess pain on injection are the rat paw lick and mouse scratch models. In the paw lick model, the drug formulation is injected into the pad of the hindfoot, and the number of times the rat licks the paw is counted. The mouse scratch test is similar except that the formulation is injected subcutaneously on the back, and the number of times the mouse scratches the injection site is counted. 

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