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CHAPTER OBJECTIVES

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  • Describe the biopharmaceutic factors affecting drug design.

  • Define the term “rate-limiting step” and discuss how the rate-limiting step relates to the bioavailability of a drug.

  • Differentiate between the terms solubility and dissolution.

  • Differentiate between the concept of drug absorption and bioavailability.

  • Describe the various in vitro and in vivo tests commonly used to evaluate drug products.

  • Describe the statistical methods for comparing two dissolution profiles for similarity.

  • List the USP dissolution apparatus and provide examples of drug products for which the dissolution apparatus might be appropriate.

  • Define sink conditions and explain why dissolution medium must maintain sink conditions.

  • Define in vitro–in vivo correlation (IVIVC) and explain why a Level A correlation is the most important correlation for IVIVC.

  • Define clinically relevant drug product specifications and describe the methods to establish them.

  • Explain the biopharmaceutic classification system and how solubility, dissolution, and permeation apply to BCS classification.

  • Provide a description of some common oral drug products and explain how biopharmaceutic principles may be used to formulate a product that will extend the duration of activity of the active drug.

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Biopharmaceutics is the study of the physicochemical properties of the drug and the drug product, in vitro, as it relates to the bioavailability of the drug, in vivo, and its desired therapeutic effect. Biopharmaceutics thus links the physical and chemical properties of the drug and the drug product to their clinical performance, in vivo. Consequently, a primary concern in biopharmaceutics is the bioavailability of drugs. Bioavailability refers to the measurement of the rate and extent of active drug that becomes available at the site of action. For the majority of orally administered drugs, the site of action is within the systemic circulation and the drug must be absorbed to achieve a pharmacological response. Oral drug absorption involves at least three distinct steps: drug release or dissolution from the drug product in the body’s fluids, permeation of the drug across the gastrointestinal (GI) linings into the systemic circulation, and drug disposition during GI transit (eg, GI stability, motility, metabolism, etc). Additional drug disposition may occur in the systemic circulation and thus reduce the concentration of drug available to the target tissues. However, because the systemic blood circulation ultimately delivers therapeutically active drug to the tissues and to the drug’s site of action, changes in oral bioavailability affect changes in the pharmacodynamics and toxicity of a drug.

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A drug product may also be designed to deliver the drug directly to the site of action before reaching the systemic circulation, which is often termed locally acting drug. Some examples of products in this class include ophthalmic, pulmonary, and nasal drug products. Similar to systemic bioavailability, local drug bioavailability is strongly influenced by physicochemical properties of the drug and drug product, the rate and extent of drug release from the drug product, and permeation at the target site (eg, skin physiology compared with that in the cornea). Regardless ...

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