Types of parenteral dosage forms

Types of parenteral dosage forms

Small-volume parenterals versus large-volume parenterals

Injectable parenteral drug products are available as single or multiuse containers in different container–closure systems and volumes. Small-volume parenterals (SVPs) are available in volumes of less than 1 ml, and up to 50 ml. Large-volume parenterals (LVPs) are usually packaged in volumes up to 1000 mL.

SVPs include both unit-dose and single-dose and multidose containers. Unit dose containers are usually hermetically sealed ampoules that are intended to be discarded after a single injection. Multidose containers, on the other hand, are usually rubber-stoppered and sealed glass vials that are intended for multiple injections. The drug for each injection is withdrawn by inserting the needle through the rubber stopper, which self-seals after the needle is withdrawn.

SVPs for IV injection may not be isotonic because the large volume of blood rapidly dilutes them. However, hypertonic solutions tend to be tissue irritants. The pH of SVPs can also vary from the physiological pH because the blood buffering system rapidly readjusts the pH after a small volume injection. SVPs for single-dose administration may be free of antimicrobial preservatives, but multidose vials usually have the preservatives to ensure sterility over multiple uses over a certain period of time.

Injections versus infusions

Injection and infusion are the predominant methods of parenteral admin-istration. Injection via different routes of administration usually utilizes a SVP. An infusion involves the IV administration of a LVP over a prolonged period of time. Infusions are commonly used for fluid replacement, admin-istration of drugs with a short plasma half-life, and/or dilution of a drug immediately before administration.

Types of formulations

Parenteral products can be formulated as solutions, suspensions, emulsions, or lyophilized products (solid) for reconstitution immediately before use.

1. Solutions

Most injectable products are solutions. Although usually aqueous, they may also contain cosolvent(s), such as glycols (e.g., polyethylene glycol [PEG] or propylene glycol), alcohols (e.g., ethanol), or other nonaque-ous solvents (e.g., glycerin). These solutions are usually filtered through a 0.22 μm membrane to achieve sterility. Solutions that do not contain any antimicrobial agents should be terminally sterilized. Autoclaving is the preferred method for terminal sterilization whenever drug solutions can withstand heat. An antimicrobial agent is often added to SVPs that cannot be terminally sterilized.

2. Suspensions

Parenteral suspensions should be easily resuspended and passed through an 18 to 21-guage needle throughout their shelf lives. To achieve these prop-erties, it is necessary to select and carefully maintain particle size distri-bution, zeta potential, rheological properties, and wettability. Injectable suspensions often consist of the active ingredient suspended in an aqueous vehicle containing an antimicrobial preservative, a surfactant, a suspending agent, a buffer, and/or a salt.

Due to the inherent long-term physical instability of suspensions, parenteral suspension dosage forms are formulated as dry powders for reconstitution immediately before administration. The sterile dry powder could be produced by freeze-drying, sterile crystallization, or by spray-drying. Parenteral sus-pensions are prepared by mixing dry powders in sterile vehicles immediately before administration. Examples of parenteral suspensions include penicillin G procaine injectable suspension USP and testosterone injectable suspension USP.

Lyophilization or freeze-drying is used to prepare powder cakes for reconstitution immediately before administration. It has inherent advan-tages over other methods of preparation of dry powders, such as

·           Water is removed at low temperatures, avoiding damage to heat-sensitive drugs.

·           Freeze-dried product usually has high-specific surface area, facilitat-ing rapid reconstitution.

·           Freeze-dried dosage form allows drugs to be filled into vials as a solu-tion, which can then be freeze dried into the final, marketed dosage form. Thus, it does not require powder filling, which is technologi-cally more challenging than filling solutions.

Despite the advantages of freeze-drying, cautions must be taken for lyophi-lizing proteins, liposomal systems, and vaccines, because they tend to get damaged by freezing, freeze-drying, or both. These damages can often be minimized by using protective agents, such as polyols, polysaccharides, disaccharides and monosaccharide.

3. Emulsions

Because emulsions can cause pyrogenic reactions and hemolysis, and require autoclave sterilization in addition to their inherent physical insta-bility, their use as IV dosage forms has been limited. Total body nutri-tion is often administered as an IV emulsion to enable coadministration of both water-soluble and water-insoluble nutrients. IV fat emulsion usually contains 10% oil. Fat emulsions yield triglycerides that provide essential fatty acids and calories during total parenteral nutrition of patients who are unable to absorb nutrients through the GI tract. IV lipid emulsions are usually administered in combination with dextrose and amino acids in the aqueous phase.