Injected drugs depot

Key words drug delivery, targeted cancer chemotherapy, injectable drug depot, nanoparticles. 

Figure 3.27 Example of a Pt-DACH thermosensitive cyclotriphosphazene injectable drug depot...

Within the area of biological treatments it is especially important to analyze the non-pharmacological factors of psychopharmacology, which include the fact that prescription patterns vary from one ethnic group to another colored patients in the United States receive greater doses of neuroleptic drugs and injectable or depot forms are more frequent than oral medication (Alarcon, 2005) how side effects are perceived and reported are strongly affected by the patient s (culturally... 

The requirement of 3 mg/day of carmustine over 20 days means a load of up to 60 mg in a device. Most formulations would suggest no higher than a 10% load of drug in the polymer matrix, so that the entire drug depot would be approximately 0.6 mL in volume. This is a very modest size disk, of about 0.1 x 2.5 x 2.5 cm. Or this amount of drug can be packaged into numerous injectible microspheres of 300 ttm... 

Complications at the site of injection of depot neuroleptic drugs, including pain, bleeding or hematoma, leakage of drug from the injection site, acute inflammatory induration, and transient nodules, have been reported (SEDA-20, 43). 

Corticosteroids also may be delivered by injection. The intramuscular route is preferable in patients with compliance problems, since a depot effect is achieved. Depot forms of corticosteroids include triamcinolone acetonide, triamcinolone hexacetonide, and methylprednisolone acetate. This provides the patient with 2 to 8 weeks of symptomatic control. The depot effect provides a physiologic taper, avoiding withdrawal reaction associated with hypothalamic-pituitary axis suppression. It should be noted that the onset of effect via this route may be delayed by several days. Intravenous corticosteroids may be used to provide the patient with large amounts of drug during a steroid burst to control severe symptoms. Intra-articular injections of depot forms of corticosteroids can be useful in treating synovitis and pain when a small number of joints are affected. The onset and duration of symptomatic relief are similar to those of intramuscular injection. The intra-articular route often is preferred because it is associated with the fewest number of systemic adverse effects. If efficacious, intra-articular injections may be repeated every 3 months. No one joint should be injected more than two to three times per year because of the risk of accelerated joint destruction and atrophy of tendons. Soft tissues such as tendons and bursae also may be injected. This may help control the pain and inflammation associated... 

Ininiiniiscular and subcutaneous injections. Drugs in aqueous solution arc usually absorbed fairly rapidly, but absmption can be slowed by giving the drug in the form of an e.ster(e.g. neuroleptic depot preparations. Chapter 27). 

Injectibles are in-situ semisolid drug depots that have been developed for drug delivery. This system has overcome several of the limitations associated with other drug-delivery systems discussed in preceding subsections. Injectibles are composed of biodegradable products that are injected into the body through a syringe once introduced into the body, these products solidify to form a semisolid depot [75]. Several types of... 

Drug formulations In patients, mean age 73 years, with prostate cancer, a study of the use of leuprorelin acetate 11.25 mg injections every 3 months for 12 months ( = 58), compared with six monthly injections of depot leuprorelin acetate containing either 22.5 or 30 mg ( = 120), the results suggested no differences in adverse reactions [10 ]. Rushing was the most common adverse reaction it occurred in 43% of those who received 11.25 mg and in 34% of those who received 30 mg. Increased sweating was also slightly more common in those who received 11.25 mg. Injection site... 

ELP form aggregates at 37°C and form 34 a drug depot that slowly disaggregate and cleared from the joint space over time Biodistribution studies showed that the aggregating ELP exhibited 25-fold longer half-life in the injected joint. Thus, a prolonged release of the incorporated drug could be obtained. 

Thennosensitive polymers have been developed extensively over the past years l-4. In particular, polymers showing a sol-gel transition by temperature change have been proposed for an injectable drug delivery depot [5,6]. As an example of temperature sensitive polymers, aqueous solutions of commercially available poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO Pluronics (BASF) or Poloxamers (ICI)) demonstrated sol-gel phase transitions with increasing temperature. 

An example of such a product is Sterile Medroxyprogestrone Acetate Suspension used for its contraceptive property. Such an injection is designed to provide up to three months of contraceptive activity. Another such product is a depot injection of leuprolode acetate, an analogue of gonadatropin-releasing hormone (see Drug delivery systems). In this case, the product is a sterilized powder of microspheres to be suspended upon the addition of an appropriate diluent and intended for monthly injection. 

Oil-soluble derivatives of testosterone itself predate those of its 19-nor congener these agents too are used to administer depot injections so as to provide in effect long-term blood levels of drug. Thus, acylation of testosterone with propionyl chloride in the presence of pyridine yields testosterone propionate (76a)acylation by means of decanoic anhydride yields testosterone decanoate (76b).Finally, reaction of 75 with 3-cyclopentylpropionyl chloride affords testosterone cypionate (76c)This last undergoes hydrolysis unusually slowly because of the presence of two substituents at the 5 position (see Newman s Rule of 6). ... 

Intramuscularly administered products typically form a depot in the muscle mass from which the drug is slowly absorbed. The peak drug concentration is usually seen within 1-2 hours. Factors affecting the drug-release rate from an IM depot include the compactness of the depot (the less compact and more diffuse, the faster the release), the rheology of the product, concentration and particle size of drug in the vehicle, nature of the solvent or vehicle, volume of the injection, tonicity of the product, and physical form of the product. 

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

Although the time to peak drug concentration is often on the order of 1 to 2 h, depot preparations given by IM injection are absorbed extremely slowly. Numerous... 

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