Excipient injectable formulations

Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res 2004 21 201. 

Excipients used in injectable formulations have to meet several stringent requirements. A positive identification test uniquely applicable to the excipients is required (e.g., infrared spectrophotometry and chromatography). It is important that manufacturers identify and set appropriate limits for impurities. These limits should be based upon appropriate toxicological data, or the limits described in national compendial requirements. Manufacturing processes should be adequately controlled so that the impurities do not exceed such established specifications. Solvents or catalysts used in the excipient production process should be removed to appropriate levels. If naturally derived, excipients should meet endotoxin levels and may require further testing for bovine spongiform encephalopathy (BSE) /... 

Naturally this is not a standard rule, because other excipients and the drug itself may also play a role in the phenomenon. Some of the buffers commonly used for injectable formulations are listed in Table 6. 

Strickley (2004) has compiled a comprehensive review of solubilizing excipients, including surfactants, in various oral and injectable formulations. 

Tables 4 and 5 are lists of selected, commercially available aqueous-based and non-aqueous injectable formulations, respectively, arranged alphabetically by drug name and also showing the drug s chemical structure, the formulation with the list of excipients, administration preparation, the dose, and the estimated maximum amount of each excipient administered, if...

Table 6 Solubilizing excipients used in commercially available solubilized injectable formulations...

Macrogol 15 hydroxystearate is used in parenteral pharmaceutical preparations in concentrations up to 50% to solubilize diclofenac, propanidid, and vitamin Kl. It has also been used in preclinical formulations in preparing supersaturated injectable formulations of water-insoluble molecules. It is generally regarded as a relatively nontoxic and nonirritant excipient. 

Strickley RG. Solubilizing Excipients in Oral and Injectable Formulations. Pharm Res OOA 21 201-230. 

Parenteral is defined as situated or occurring outside the intestine, and especially introduced otherwise than by way of the intestines —pertaining to essentially any administration route other than enteral. This field is obviously too broad for an adequate focus in one book, let alone one chapter. Many have nonetheless used the term synonymously with injectable drug delivery. We restrict ourselves to this latter usage. This would thus include intravenous, intramuscular, subcutaneous, intrathecal, and subdural injection. In this chapter we discuss the theoretical and practical aspects of solubilizing small molecules for injectable formulation development and will examine the role of surfactants and other excipients in more recent parenteral delivery systems such as liposomes, solid-drug nanoparticles and particulate carriers. 

Since the administration routes are mainly parenteral, the formulation has to be injectable. An injectable formulation requires specific excipients, ways of preparation and formulation types liquid, suspension, or solid formulations. In the development of protein drugs, various formulation principles are used. In Table 5, examples of some of the formulation principles are given. 

Other additives such as antimicrobial agents, antioxidants, buffers and tonicity-adjusting agents can be included in injection formulations and it is the responsibility of the pharmacist to check that all excipients and adjuvants are suitable (benzyl alcohol, ethanol, sulfites, sodium content, etc.). Nevertheless, one is left with a difficult choice over excipients, either those for which toxicity is known and therefore predictable, or those with safety profiles that have not been established in children (see under Critical excipients, page 55). The pH and osmo-larity of the preparation must also be checked before administration by another route. 

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