Antipsychotics administration routes

Other orthopramides have been shown to be resistant to in vivo hydrolysis. Thus, the gastrokinetic drug cisapride (4.80) was not hydrolyzed after oral administration to dogs and humans [51]. Similarly, sulpiride (4.81), an antidepressant and antipsychotic drug, did not undergo hydrolysis in humans and laboratory animals. These compounds are metabolized by other routes, and hydrolysis of the amide bond, when it occurs at all, is only a minor pathway. 

The chronic administration of molecules, which have a short biological half-life and cannot be given orally, presents a difficult challenge to formulators. One strategy which might be considered is the development of a sustained-release intramuscular or subcutaneous injection. Other non-parenteral options could include the inhalation or intranasal route, both of which have their own unique challenges. Sustained-release parenteral formulations might also be required in circumstances where patient compliance is likely to be poor. This consideration has led to the development of some antipsychotics and contraceptives as sustained-release injections. Table 9.6 lists some of the sustained-release parenteral products which are available on the U.S. market and their respective formulations. The typical approaches used in the formulation of sustained-release parenterals are summarised in this section. 

Phenothiazines, which are frequently antihista-minic as well as antipsychotic, concentrate in lung tissue after any route of administration. Subcutaneous or intravenous injection of chlorpromazine into ratSy rabbits, and guinea pigs resulted in a similar pattern of distribution (Berti and Cima 1955, Hackman et al. 1970). Studies in the cat showed similar concentrations of chlorpromazine in the lung, which remained almost constant from 1 to 48 h after intravenous injection (Gothelf and Karczmar 1963). 

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