Dosage forms inactive ingredients

The therapeutically inactive ingredients in ophthalmic solution and suspension dosage forms are necessary to perform one or more of the following functions adjust concentration and tonicity, buffer and adjust pH, stabilize the active ingredients against decomposition, increase solubility, impart viscosity, and act as solvent. The use of unnecessary ingredients is to be avoided, and the use of ingredients solely to impart a color, odor, or flavor is prohibited. 

The choice of a particular inactive ingredient and its concentration is based not only on physical and chemical compatibility, but also on biocompatibility with the sensitive and delicate ocular tissues. Because of the latter requirement, the use of inactive ingredients is greatly restricted in ophthalmic dosage forms. 

The FDA s regulations define drug product as a finished dosage form, for example, a tablet, capsule, solution, etc., that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredients. 21 C.F.R. 210.3(4). 

Medicines, except for goods solely for export or for use in clinical trials. The requirements include names and quantities of active ingredients, dosage form, batch number, expiry date, the registration or listing number (AUSTR or AUSTL number, respectively), identification of inactive ingredients, what labelling is adequate for special packs and small containers, and letter size and additional requirements in particular circumstances. 

There are many factors that can affect the stability of a pharmaceutical product. These include the stability of the active drug(s), interactions between active and inactive ingredients, the dosage form, manufacturing process, the container system, and environment for shipping, handling, and storage. 

Compendia that describe excipients used for various formulations such as parent-erals, vaginal formulations, and antibiotics are offered in a number of publications (7-9). The FDA publishes on its internet site, www.fda.gov, the downloadable Inactive Ingredient Database. The components of proprietary inactive ingredients are not always included. All inactive ingredients that are present in currently approved final dosage form in drug products are listed. Whenever included, one may need to search for such data under individual component entries. 

The inactive ingredients are updated quarterly, by the fifth working day of April, July, October, and January. To search for the excipient, one can enter any portion of the name of an excipient, of at least three characters. Search results are displayed alphabetically, sorted first by ingredient, then by the route of administration and dosage form. Routes of administration and dosage forms are derived from current approved labeling. Refer to the IIG query search results column headers for data field definitions. 

Choosing an acceptable preservative when developing an oral liquid formulation is primarily limited by the number of approved excipients. As Table 10 demonstrates, there are many preservatives listed in the FDA inactive ingredient guide for dosage forms other than oral liquids however not many have been commonly used in oral solutions or suspensions. 

Chemical or pharmacological equivalence - Two or more drug products which contain the same chemical compound in the same amount in two or more dosage forms and meet official FDA standards are said to be chemically equivalent. Note, however, that the "inactive" ingredients may be different. 

An inactive ingredient in the final dosage form that does not significantly affect the release of the active drug substance from the dosage form. 

CDER-approved products are considered those subject to an approved NDA or ANDA. Some information on which components/materials aie used in CDER-approved products is available from the Agency (e.g., FDA, CDER, Inactive Ingredient Guide, 1996, Division of Drug Information Resources). When infonnation is not available, an applicant should use reliable sources of infonnation to determine that the component or material has been used in and has been in contact with a CDER-approved product of the same dosage form and route of administration, as appropriate. The applicant should identify in the supplement or annual report the basis for the conclusion that the component or material is used in a CDER-approved product. 

Pharmaceutical excipients (inactive ingredients) are substances other than the active drag substance or the drug product that have been evaluated for safety and are included in the pharmaceutical dosage form (drug delivery system) for one or more of the following functions ... 

A matrix system consists of active and inactive ingredients that are homogeneously mixed in the dosage form. It is by far the most commonly used oral CR technology, and the popularity of matrix systems can be attributed to several factors. First, unlike reservoir and osmotic systems, products based on matrix design can be manufactured using conventional... 

Active and inactive ingredients are not in exactly the same proportion between different strengths as stated above, but the ratios of inactive ingredients to total weight of the dosage form are within the limits defined by the SUPAC-IR and SUPAC-MR guidances (up to Level II). 

For modified-release tablets, when the drug product is in the same dosage form but in a different strength, is proportionally similar in its active and inactive ingredients, and has the same drug release mechanism, an in vivo BE determination of one or more lower strengths can be waived based on dissolution profile comparisons, with an in vivo... 

State the composition the name and amount of each active and inactive ingredient in the drug product in the form in which it is to be distributed (e.g., amount per tablet). Describe the dosage form full details as to type and physical characteristics (e.g. shape, color, coating, and hardness). 

A quantitative composition, including the name and amount of each active and inactive ingredient contained in the drug product, should be provided. In addition, an overall description of the dosage form should be included. This should be in sufficient detail to characterize it fully with regard to its type, release properties (i.e., immediate versus sustained or controlled release), and physical characteristics such as shape, color, type of coating, hardness, scoring, and identification marks. 

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