Suspensions parenteral

In contrast, parenteral suspensions have relatively low solids contents, usually between 0.5 and 5%, with the exception of insoluble forms of penicillin in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intralesional, intraarticular, or subcutaneous injection. Syringeability is an important factor to be taken into consideration with injectable dosage forms. The viscosity of a parenteral suspension should be sufficiently low to facilitate injection. Common suspending vehicles include preserved isotonic saline solution or a parenterally acceptable vegetable oil. Ophthalmic and optic suspensions that are instilled into the eye/ear must also be prepared in a sterile manner. The vehicles are essentially isotonic and aqueous in composition. The reader should refer to Chapter 12 for further discussion on parenteral products. 

Due to particle sizes in the micrometer range, parenteral suspensions are generally limited to either subcutaneous or intramuscular routes of administration. However, ultrafine suspensions can be approached by high-pressure homogenization [200]. The particle size obtained from this technique is in the 100 500 nm range, thus intravenous administration is possible [201]. General information on parenteral formulations is given in Chapter 12. 

If the solubility of a drug is to be reduced to enhance stability or to prepare a suspension, the for-mulator may prepare water-insoluble salts. A classic example is procaine penicillin G, the decreased solubility (7 mg/mL) of which, when compared with the very soluble penicillin G potassium, is utilized to prepare stable parenteral suspensions. Another alternative to preparing an insoluble drug is to use the parent acidic or basic drug and to buffer the pH of the suspension in the range of minimum solubility. 

A surfactant is a surface-active agent that is used to disperse a water-insoluble drug as a colloidal dispersion. Surfactants are used for wetting and to prevent crystal growth in a suspension. Surfactants are used quite extensively in parenteral suspensions for wetting powders and to provide acceptable syringability. They are also used in emulsions and for solubilizing steroids and fat-soluble vitamins. 

Two basic methods are used to prepare parenteral suspensions (a) sterile vehicle and powder are combined aseptically, or (b) sterile solutions are combined and the crystals formed in situ. Examples of these procedures may be illustrated using Penicillin G Procaine Injectable Suspension USP and Sterile Testosterone Injectable Suspension USP. 

An example of the second method of parenteral suspension preparation is testosterone suspension. Here, the vehicle is prepared and sterile-filtered. The testosterone is dissolved separately in acetone and sterile-filtered. The testosterone-acetone solution is aseptically added to the sterile vehicle, causing the testosterone to crystallize. The resulting suspension is then diluted with sterile vehicle, mixed, the crystals allowed to settle, and the supernatant solution siphoned off. This procedure is repeated several times until all the acetone has been removed. The suspension is then brought to volume and filled in the normal manner. 

Akers, M.J., Fites, A.L., and Robinson, R.L., Formulation design and development of parenteral suspensions, Bull. Parent Drug Assoc., 41, 88, 1987. 

Parenteral suspensions (injection) Exact dose 100% compliance Suitable for unconscious patient Rapid onset, especially after intravenous administration Painful Self-administration vmusual Requires trained personnel Solutions, emulsions, implants Expensive production processes... 

Kollidon 17 PF is eminently suitable for improving the wetability of the active substance in parenteral suspensions, e.g. penicillin ampoules. It reduces the sedimentation rate and improves the dispersability. Kollidon 17 PF, in the amounts used for this purpose, exerts practically no influence on the viscosity. 

Defelippis, M. R., and Akers, M. J. (2000), Pharmaceutical Formulation Development of Peptides and Proteins Peptides and Proteins as Parenteral Suspensions An Overview of Design, Development, and Manufacturing Considerations, Taylor and Francis, Philadelphia. 

However, because it is important that a majority of drug particles in parenteral suspensions are below 10 pm, fluid energy grinding is the most convenient method for their production. 

Structured vehicles are usually not considered for the preparation of parenteral suspensions because, owing to their high viscosity, such systems lack sufficient syringe ability for ease of use. 

An important property of a good parenteral suspension is syringeability the ability of a parenteral solution or suspension to pass easily through a hypodermic needle, especially during the transfer of a product from vial to hypodermic syringe prior to injection. Increases in vehicle viscosity, vehicle density, and size and concentration of suspended particles make the transfer more difficult. 

Resuspendability, or the ability to distribute settled particles with a minimum of shaking, is an important characteristic of parenteral suspensions. Stable, flocculated parenteral suspensions that have been undisturbed for long periods of storage time are easily resuspended. 

The drug concentration in a parenteral suspension can influence the plasma concentration profile. When different concentrations of amoxicillin (100 and 200mg/ml) in aqueous suspensions of amoxicillin trihydrate were administered intramuscularly at the same site and same dose level (lOmg/kg) to horses, the preparation of lower concentration (10%) provided relatively better absorption and a more consistent plasma concentration profile. Intramuscular injection of amoxicillin trihydrate (15% in a mixed oil base) in the neck (10 cm behind the ear) of pigs produced two peaks, 1.7 and 0.8pg/ml at 1.3 and 6.6 h, respectively, rather than a single peak in the plasma concentration profile and an eight-fold longer mean residence time of the antibiotic than a preparation of the same... 

Low-molecular povidones can be used as dispersing agents for parenteral suspensions (crystalline suspensions, lyophilisates, nanoparticles) [115,116,120-122, 633]. These endotoxin-free grades have been developed specially for parenterals and produce suspensions with about the same physical properties as, for example, povidone K 30, except that their viscosity is somewhat lower. 

Some typical active ingredients combined with low molecular weight povidone in commercialized parenteral suspensions are benzylpenicillin, fluspirilen, penicillin and streptomycin. 

Table 7 is a current listing of parenteral suspension products. 

This approach can be used to prolong the release of compounds with limited aqueous solubility. A suspension of a compound in its saturated solution can provide both immediate-release and sustained-release components of a dose (Madan 1985). A number of water-insoluble prodrugs are also formulated as suspensions, including hydrocortisone acetate and medroxyprogesterone acetate. As with any other type of suspension, excipients will usually be required to ensure the physical stability of the formulation. Strickley s (1999) article provides a table of parenteral suspension formulations the most popular excipient combinations are clearly polyethylene glycol/Tween 80 and carboxymethylcellulose/Tween 80. 

Perhaps the most well-known example of a parenteral suspension formulation is insulin. Many insulin formulations also take advantage of the different physical forms which can be produced when insulin is complexed with zinc. Suspensions of the amorphous form of insulin zinc have a faster onset of action and shorter duration of action compared to those of the crystalline form. In order to provide both a rapid onset and a long duration of action, many formulations are composed of a mixture of amorphous and crystalline zinc insulin. 

Other routes of administration arc theoretically possible such as rectal route (rectal capsules and rectal suppositories) for drugs having systemic effects such a.s sedatives, tranquilizers, and analgesics topical route (patchs) for drug absorption (hormones or nicotine) into the systemic circulation parenteral route (administration of parenteral suspensions or implantation of compressed pellets). 

---