Dosage forms comparative bioavailability

Equation (41) is useful for comparing the bioavailabilities of two dosage forms of the same drug administered to the same group of subjects. If it is... 

WJ Westlake. The design and analysis of comparative blood-level trails In J Swarbrick, ed. Current Concepts in the Pharmaceutical Sciences Dosage Form Design and Bioavailability. Philadelphia, PA Lea Febiger, 1973. 

The information requirements for products such as prolonged-release oral dosage forms will depend on whether or not it has been possible, during the development of the product, to establish an in vivo-in vitro correlation between clinical data and dissolution studies. In vivo-in vitro correlations should be attempted using product at different stages of development, but bioavailability and pharmacokinetics data from pivotal clinical studies using at least pilot-scale production materials and possibly routine production material are particularly important. Where it is not possible to establish an in vivo-in vitro correlation, additional data will be required to compare the bioavailability of product developed at laboratory scale, pilot scale, and production scale. In the absence of an in vivo-in vitro correlation, the dissolution test will be a quality control tool rather than a surrogate marker for in vivo performance of the product. 

Product bioavailability is mentioned, especially where it is low. Where there are differences between the formulations tested for bioavailability during the development process and the formulation to be marketed, there is considerable discussion of the data provided on the bioequivalence of the different products and/or formulations. This is particularly so where, for example, early clinical studies were undertaken with capsules but the marketed dosage form is to be a tablet. Bioequivalence data and pharmacokinetic data (e.g., in crossover studies) and comparative dissolution studies are usually reported. This is particularly significant where the different strengths of the final products are not achieved by using different quantities of the same granulate formulation. Process optimization may also be addressed in such cases. 

Comparative bioavailability data are discussed where a number of different dosage forms/routes of administration have been used during the development process, e.g., tablets, capsules, oral solutions, granules, and injections. 

When delivered parentally or orally, a drug in solution is more rapidly bioavailable compared to a solid dosage form. The cosolvent approach also has some limitations as pointed out for other solubilization techniques. When solubilization of a drug is achieved by use of cosolvent, it must meet certain requirements, such as nontoxicity, compatibility with blood, nonsensitizing, nonirritating, and above all physically and chemically stable and inert. 

Bioavailability studies using animals are used to compare the efficiency of the delivery of the dosage forms of a drug to the general circulatory system as well as the efficiency of the route of administration for both licensed drugs and new drugs under development. Two useful measurements are relative and absolute bioavailability. 

Relative availability. Relative bioavailability may be used to compare the relative absorptions of the different dosage forms of the same drug and also the relative availabilities of two different drugs with the same action when delivered using the same type of dosage form. It is defined for equal doses as ... 

Our first stereospedfic bioequivalence evaluation using verapamil formulations was a pilot study conducted in 24 healthy male volunteers. The study compared the bioavailability of two sustained-release dosage forms and an immediate release formulation of racemic verapamil in a three-way cross-over study. Table 2 summarizes the results observed for verapamil. Table 3 the results for norverapamil. First, pharmacokinetic... 

Aqueous solutions, syrups, elixirs, and emulsions do not present a dissolution problem and generally result in fast and often complete absorption as compared to solid dosage forms. Due to their generally good systemic availability, solutions are frequently used as bioavailability standards against which other dosage forms are compared. 

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