Depot parenteral preparations

One of the main disadvantages of depot parenteral preparations is that administration of these preparations may not be acceptable to the patient. The depot preparation requires a lower dosing frequency when compared with other dosage forms. 

The oral contraceptives are of two main types the combined hormonal contraceptives containing both an oestrogen and a progestogen (monophasic, biphasie, triphasie, or sequential), available as tablets or a patch, and the progestogen-only contraceptives, which are available as tablets (sometimes ealled mini pills), parenteral preparations (implants, depot injections) and intrauterine devices. 

It should be pointed out that cubic phases, such as the one discussed in this work, frequently occur in lipid-water systems (77), and the concept of using cubic phases as drug vehicles is therefore not limited to the use of monoolein only. From a toxicological stand-point, it is tempting to try to use membrane lipids, such as phospholipids, instead of monoolein for parenteral depot preparations (18-20). 

Improvement of the properties of a drug may be achieved by the chemical modification of the parent drug. The preparation of an ester, salt, or other modification of the parent structure may be employed with parenteral drugs to increase stability, alter drug solubility, enhance depot action, avoid formulation... 

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). 

Huphenazine is a short acting agent. Eor the management of agitated and potentially violent patients its hydrochloride formulation is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot preparation. Although its principal pharmacological activities are similar to those of the other phenothiazines fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive effect. 

Betamethasone is hardly ever used orally. It has a long duration of activity and can therefore also be used for alternate-day therapy. The parenteral formulation is also the sodium phosphate salt which when given IV or IM has a rapid onset of action. There are many similarities with dexamethasone such as their metabolic pathways and the indications for which both steroids are used, like the prevention of neonatal RDS and reduction of raised intracranial pressure. Combinations of betamethasone acetate and sodium phosphate have, when used for intra-articular and intra-lesional injections, the dual advantage of a rapid onset of action together with the long duration of action of a depot preparation. 

Polymeric micropsheres, particularly those prepared from the biodegradable polylactide/ polyglycolide polymers, have been widely investigated as a means to achieve sustained parenteral drug delivery. The advantage of formulating the polymeric matrix as microspheres is the ability to administer them via a conventional needle and syringe as a suspension formulation, rather than as an implant (see below). Lupron depot formulations are available which can provide therapeutic blood levels of leuprolide acetate for up to four months. These products are presented as lyophilized polylactic acid microspheres which are reconstituted to form a suspension prior to administration. 

L. inflata (Indian tobacco) is indigenous to the Eastern and Central states of USA and Canada. The plant contains ca. 0.3% of alkaloids. The L. a. are 2,6-di-substituted piperidine derivatives. Among the ca. 20 L. a., lobeline is the major alkaloid. When administered parenterally (3-10 mg) lobeline stimulates respiration and was used in the past as a respiratory analeptic agent for asthma, collapse, and narcosis incidents. When taken orally it is rapidly degraded and thus not effective. Since lobeline potentiates the action of nicotine and induces nausea and revulsion it has been developed clinically in depot form in antismoking preparations. - The piperidine ring is biogenetically derived from lysine and the substituents from phenylalanine. 

Among the various approaches, major emphasis has been directed toward the development of parenteral repository or depot antimalarial substances. Such preparations consist typically of suspensions of repository compounds in aqueous or lipid vehicles. When these suspensions are injected intramuscularly or subcutaneously, the insoluble material is deposited in the tissues, forming a depot from which active principles are very slowly released into the circulation. In preparations of this type, it is essential that candidate substances be nonirritating to the tissues and imdergo minimal encapsulation. 

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