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Date of Award


Document Type


Degree Name

Master of Science (M.S.)


Graduate School


The Food, Drug, and Cosmetic Act of 1938 required a producer of a new drug to substantiate the safety of the drug product when used as recommended; however, the introduction of the Kefauver-Harris Amendments of 1962 considerably strengthened this act. These amendments intensified the controls on quality, labeling, and safety, while adding a new requirement that all NDA's should be able to present substantial evidence of the effectiveness of the drug product for its indicated use of uses (4). The procedure used to determine the efficacy of a drug included identification of the product, copies of the labeling, and a bibliography of publications substantiating the claims made for the drug. The manufacturers were also requested to submit any unpublished information to further substantiate the claims made for the drug product (5,6). Bioavailability is a complex problem due to the many variables associated with the development of drug dosage form design. The bioavailability of a drug product can be influenced by pharmaceutical formulation factors as well as by the physiological factors of the patient taking that drug product.

Compressed tablets are the mostly widely used of all the dosage forms, and they present the most problems in regard to the bioavailability of the active component. This is especially true for those compressed tablets that contain drugs with a low solubility, a low rate of solution, drugs which exhibit poor absorption characteristics, drugs which are unstable in the gastrointestinal environment or drugs that are used in large dosage (25).

The significance of a bioavailability study is established when a correlation is demonstrated between the blood levels achieved using a drug already shown to be clinically effective and the drug product being tested (34). This type of relationship tends to indicate that the drug product being tested would be therapeutically equivalent to the reference drug product (35).

Bioavailability data is necessary for the establishment of therapeutic equivalency among drug products. Consequently, bioavailability data is necessary for the establishment of therapeutic equivalency among drug products; particularly for those drug products most often prescribed.

Phenobarbital tablets have been listed among the top 5 generic products, by new prescription volume, for the last 4 years. In addition, phenobarbital tablets have been the leading drug product amon the top 20 generic products by refill prescription volume over the last 4 years. Of the top 20 generic products by new and refill prescription volume, phenobarbital products have ranked among the top 3 for the past 4 years. Furthermore, phenobarbital tablets have been listed among the top 4 drug products in a list of the average retail new prescription prices for the top 20 generic products in the last 4 years (36).

From a physiochemical basis, the bioavailability of phenobarbital tablets has been suspect.

The incomplete data available on phenobarbital tablets indicated the necessity for determining the physical properties and the bioavailability of these products. Therefore, Phenobarbital Tablets, USP, 100 mg, were obtained from 7 manufactures to characterized the physical properties of tablet weight, hardness, disintegration time , and dissolution rate; to determine the bioequivalency, bioavailability studies were conducted employing 5 normal, healthy human adult male subjects.