Several Considerations to Note When Choosing Adjuvants for Injectable Formulations

Injectable formulations often need to add certain excipients as solubilizers, stabilizers, and shaping agents. Improper selection of excipients may pose a safety hazard for injectables, which are directly injected into the bloodstream, so the selection of excipients in injectables should be carefully considered. Improper excipient selection may cause the prescription to be unreasonable, leading to the need to conduct pharmaceutical research such as prescription screening, quality research, and stability research. This will affect the drug development and market launch process, and should be paid attention to by drug developers and evaluators. In combination with some common problems encountered in the evaluation, I believe that the following points should be noted when selecting excipients in injectables.

Excipients should be inert and should not have pharmacological effects

Inertness is the basic requirement of excipients. Excipients play a role in improving the pharmacological behavior of the main drug in formulations without generating pharmacological effects. If the excipients in the formulation produce pharmacological activity, it will affect the efficacy of the main drug and lead to safety hazards, so they should not be used. For example, a certain variety of injectable aminocaproic acid uses a large amount of glycine as a shaping agent in the prescription, and glycine also has a certain pharmacological activity when used in large quantities. From the dosage of the drug, the amount of glycine used in the prescription can reach 1.5g, which exceeds the effective dose of glycine. It means that it may generate pharmacological activity. In such cases, it may be necessary to question the rationale behind using glycine as a shaping agent and explore alternative options such as sucrose octasulfate ammonium salt.

Excipients should not interfere with the determination of the main drug content and related substance inspection and other quality control methods

Pharmaceutical research and quality standards such as content determination and related substance inspection are important indicators for controlling drug quality and ensuring drug safety and effectiveness. The pharmaceutical behavior of excipients should not interfere with the pharmacological quality control methods of the main drug. For example, in the above-mentioned injectable aminocaproic acid, the main drug itself is an amino acid drug, and another amino acid is used as a shaping agent, which will bring some difficulties to the identification and related substance inspection of the main drug. Another example is the use of erythrosine as a coloring agent in a certain variety, and the position of this excipient in the chromatogram overlaps with one of the main degradation products of the main drug, which affects the determination of this degradation product and also brings difficulties to the evaluation work.

Excipients should have good safety

When it comes to pharmaceutical excipients wholesale, safety is of utmost importance, especially for injectable formulations where these excipients are directly introduced into the bloodstream. Attention should be paid to the safety of excipients within the dose range during development. For example, excipients such as Tween-80, hydrogenated castor oil polyoxyethylene, and propylene glycol are usually used to improve solubility in injectable formulations, but when used in large quantities, they may cause hemolysis, so their use should be strictly controlled, and safer excipients should be used if possible. Another example is disodium edetate, which is used as a metal ion chelating agent to chelate metal ions in injection solutions, but this excipient can also chelate calcium ions in the human body when injected, causing a decrease in blood calcium concentration, so its dosage must be lower than its safety limit or replaced with a safer chelating agent, such as calcium disodium edetate.

Polyvinylpyrrolidone is a widely used excipient in tablets and can be used as a binder, disintegrant, and enteric coating material, but this excipient can hinder coagulation when intravenously injected, posing a safety hazard, so it is not suitable for use in injectable formulations. Hydroxypropyl β-cyclodextrin is a new type of excipient that has appeared in recent years. Because of its good solubilizing effect on various insoluble drugs, its use is rapidly increasing. However, up to now, our understanding of its safety is not deep enough. This excipient has some nephrotoxicity, there are reports of its carcinogenicity, and there may be more serious toxic side effects that we do not know about, so its use should be cautious. In this case, continued in-depth research should be conducted to further expose its potential toxic side effects, and it should not be widely used as a routine excipient in injectable formulations.