Injectable products drug stability

Sterility, freedom from pyrogens, and acceptably low level of extraneous particulate matter are critical quality attributes of all injectable products. Additional critical quality attributes depend on the clinical use of the product. For example, for IV, IM, and SC routes, isotonicity and physiological pH (7.4) are always desirable in order to minimize potential irritation upon injection. Other factors may preclude this, however. If the required dose of drug must be administered in a small volume, it may not be feasible to formulate an isotonic solution. Likewise, solubility or stability considerations may preclude formulation at physiological pH. This explains why formulation pH for injectable drugs varies from about pH 2 to about pH 11. 

Some of the key factors in considering specific delivery systems are safety, stability, and efficacy. The parenteral administration of proteins and peptides today offers assured levels of bioavailability and the ability of the product to reach the marketplace first. It is safe to assume that over 95% of the protein therapeutics approved by the Food and Drug Administration (FDA) today are injectable products since parenteral administration avoids physical and enzymatic degradation. 

Homogeneous solutions are the preferred formulation systems for parenteral administration because they can be easily visually inspected for the absence of particulate matter. For this reason, cosolvent solubilization is the first choice for parenteral products once purely aqueous systems provide insufficient solvency. The compositions of three commercial, injectable products are given in Table 39.5. The first product (1) has a low percentage of cosolvent in the separate solvent ampoule. The drug substance is provided as a dry powder because of its limited stability in solution. The second one (2) is solubiUzed with two cosolvents amounting to 50% of the total volume, whereas in the third product the drug dose is dissolved in a water-free mixture of cosolvents. This draws the attention to a further point to consider when cosolvents are employed in formulations. The formulation has to be devised such that the effect of dilution of... 

The stability studies for drug injectable suspension and drug for injectable suspension products should also include particle size distribution, redispersibility, and rheological properties in addition to the parameters cited above for drug injection and drug for injection products. 

Parenterais The most important criterion for parenterals is that they have to be sterile for injection or infusion administration. Excipients are added to make parenterals isotonic with blood, improve solubility, and control pH of the solution. The solvent vehicles include water-for-injection, sterile sodium chloride, potassium chloride, or calcium chloride solution, and nonaqueous solvents such as alcohol, glycol, and glycerin. Preservatives, antioxidants, and stabilizers are normally added to enhance the properties of the drug product. 

One must also remember that precipitation can occur on dilution with other intraverarixili Investigation of dilution in common parenteral vehicles, for example, normal saline, 5% dextrose solution, or likely coadminstered drug products should be conducted for solubility and stability purposes before recommending such procedures. Phlebitis, hemolysis, and pain on injection are also issues for parenteral formulations containing cosolvents. 

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