Prolonged drug release

The advantageous effects of liposomal carrier systems include protection of compounds from metabolism or degradation, as well as enhanced cellular uptake. Liposome-mediated delivery of cytotoxic drugs to cells in culture has resulted in improved potency [58,59]. Prolonged release of encapsulated cargo has also been demonstrated [60,61]. More recently, liposomes with extended circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) [62] have shown promise in delivery of drugs that are normally very rapidly degraded. 

Sustained- and controlled-release devices for drug delivery in the vaginal and uterine areas are most often for the delivery of contraceptive steroid hormones. The advantages in administration by this route—prolonged release, minimal systemic side effects, and an increase in bioavailability—allow for less total drug than with an oral dose. First-pass metabolism that inactivates many steroid hormones can be avoided [183,184],... 

Where an unusual excipient is chosen, or where an established excipient is chosen for a dosage form that results in its administration by a novel route of administration, then additional data will need to form part of the application. In effect, a novel excipient will need to be supported by data similar to those required for a new drug, with full supporting data including composition, function, and safety. Novel excipients include the components of the matrix in prolonged release products, new propellants, and new permeability enhancers. The exception to this need for extensive supporting data would be for a material already approved for food use and administered by the oral route or a material already approved for cosmetic use with a topical route of administration. In all cases the quality of the excipients has to be described adequately and shown to be satisfactory (which will depend on its role). 

These ideas appear to merit careful consideration. Similarly, the use of nomograms to evaluate the intrinsic absorption rate constants for drugs that may be formulated into oral prolonged-release products may be of value [5],... 

The majority of oral preparations are solid dosage forms. These include tablets and capsules for administration to small farm animals, pastes for horses, and a variety of prolonged-release products for administration to cattle. The drug in solid dosage form must dissolve before it can be absorbed. The dissolution rate de-... 

There are several reports for successfully prolonged release of short half-life drugs with squalene emulsions. Wang et al. (2008) reported that a squalene emulsion stabilized by phosphatidylethanolamine or pluronic F68 prolonged in vitro release of a morphine prodrug. Intravenous... 

As has been stated earlier, physical interactions can be either beneficial or detrimental to product performance. The distinction often depends on the particular application or context. For example, what may be beneficial for a prolonged release product may be detrimental in an immediate release product, and vice versa. This type of interaction can be between the drug and the excipient(s) or between two or... 

We include certain excipients in a formulation specifically because they interact with the physiological fluids and the bodily functions in a certain way. For example, as discussed above, we include disintegrants in immediate release tablet and capsule formulations, because we know that when they encounter the aqueous environment of the stomach, they will cause the tablet or capsule to disintegrate and thereby aid dissolution of the API. Another example is the general case of hydrophilic colloid matrices used as prolonged release drug delivery systems. We know that when these materials contact the aqueous environment of the GIT they swell and create a diffusion barrier that slows the rate of dissolution of the dissolved drug. 

There are fewer reports on other parenteral routes of administration of emulsions such as intramuscular, subcutaneous, and intraperitoneal. V Mer-in-oil and w/o/w emulsions of bleomycin, mytomycin C, and 5-Luorouracil have been administered by these routes, apparently resulting in increased regional lymphatic uptake, hence the term lymphotropic emulsions (Davis et al., 1987). Gasco et al. (1990) developed a w/o emulsion of an LHRH analog measurements of testosterone levels after intramuscular administration to rats suggested that the formulation led to prolonged release of the drug. 

Intramuscular. The large quantity of skeletal muscle in the body allows this route to be an easily accessible site for parenteral administration. Intramuscular injections can be used to treat a problem located directly in the injected muscle. For example, botu-linum toxin and other substances can be injected directly into hyperexcitable muscles to control certain types of muscle spasms or spasticity (see Chapter 13).7,78 Alternatively, intramuscular injection can be used as a method for a relatively steady, prolonged release of the drug into the systemic circulation to control conditions such as psychosis,2 or to administer certain vaccines. 

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