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Definitions drug - any substance that affects the structure or functioning of an organism pharmaceutics - the area of study concerned with the formulation, manufacture, stability, and effectiveness of dosage forms pharmacology - the science of the properties of drugs and their effects on the body pharmacokinetics - the study of the kinetics of absorption, distribution, metabolism, and excretion of drugs and their corresponding pharmacologic response in animals/man clinic - a facility or area where ambulatory patients are seen for special study and treatment CHEE 440 1 PHARMACEUTICAL INDUSTRY Drug Discovery - natural sources, synthesis/modification biological properties Preclinical Studies - pharmacology, pharmacokinetics preformulation - chem/phys properties - analytical assays Formulation development of dosage form large-scale manufacturing Clinical Trials Approval for Distribution Post-Marketing Surveillance CHEE 440 2 INTRODUCTION drugs seldom administered alone objective of dosage form design CHEE 440 given as a formulation » contain additional ingredients called excipients achieve a predictable therapeutic response to a drug included in a formulation which is capable of large scale manufacture with reproducible product quality must consider physical, chemical, biological properties of all components 3 Excipients Purpose Example pH control citric acid, NaCO3 preservative NaBenzoate, phenol antioxidant surfactant ascorbic acid, NaBisulfite alcohol, sterilized water cetyl alcohol ointment base petrolatum, PEG flavor peppermint oil, menthol solvent CHEE 440 4 Need for Dosage Forms CHEE 440 provide safe and accurate delivery of given dosage protect drug from environmental degradation protect drug from GI degradation conceal bitter, salty taste, offensive odor allow for administration of poorly soluble drug provide rate-controlled action allow for admin. by desired route 5 Routes of Administration Route dosage form oral tablets, capsules, solutions, suspensions, powders, emulsions, gels, lozenges ointments, creams, pastes, lotions, gels, solutions injections (i.v., s.c., i.m., i.p., i.t., i.a, …) ointments, creams, lotions, patches, infusion pumps solutions, suspensions topical parenteral transdermal intraocular /nasal/aural pulmonary rectal vaginal urethral CHEE 440 aerosols solutions, ointments, suppositories solutions, ointments, suppositories, gels, foams solutions, suppositories 6 Drug Action QuickTime™ and a GIF decompressor are needed to see this picture. CHEE 440 7 Biopharmaceutics Bioavailability extent of absorption and the rate at which an administered dose reaches systemic circulation in its active form tissue, lymph intravenous drug in dosage form oral liver blood plasma bound free excretion metabolism site of action CHEE 440 8 example of oral administration plasma concentration time profile absorption phase elimination phase plasma conc’n time after administration CHEE 440 9 Therapeutic Window therapeutic response is dependent on drug achieving an adequate plasma concentration plasma conc’n Cp time after administration CHEE 440 10 Pharmacodynamics not all individuals respond in same manner no. of individuals minimum dose for response (mg/kg) therapeutic index (TI) CHEE 440 TI = TD50 ED50 11 absolute bioavailability any drug delivered extravascularly has the potential of being bound or eliminated before reaching bloodstream amount of drug reaching bloodstream is equal to the area under the Cp vs t curve, AUC absolute bioavailability = relative bioavailability some drugs cannot be given by iv bioavailability determined by comparison to standard dosage form relative bioavailability = CHEE 440 AUC extra AUC IV AUC test AUC s tandard 12 Bioequivalence comparison of amounts of same drug that are absorbed from 2 different formulations of the same dosage form (generics) the two formulations are considered equivalent if there is no significant difference between any of Cmax, Tmax, AUC Cp time CHEE 440 13