Introduction to Biopharmaceutics - Week 1 - Fall 2024

# Today's Class: Introduction to Pharmacy, Pharmaceutical Sciences, and Biopharmaceutics **9/8/2024** ## Today's Class will introduce you briefly to: - Pharmacy and its two key branches - Pharmaceutical Science and its key branches - Definition of pharmaceutics - Biopharmaceutics - Drugs - PK and...

# Today's Class: Introduction to Pharmacy, Pharmaceutical Sciences, and Biopharmaceutics **9/8/2024** ## Today's Class will introduce you briefly to: - Pharmacy and its two key branches - Pharmaceutical Science and its key branches - Definition of pharmaceutics - Biopharmaceutics - Drugs - PK and PD ## What is Pharmacy? - The Art, Practice and Profession of preparing, preserving, compounding, and dispensing medical drugs. - Also provides drug-related information to the public. - Subjects of Study in Pharmacy: - **Pharmacy:** - Pharmaceutical Sciences: Department of Biomedical and Pharmaceutical Sciences (BPS) - Pharmacy Practice/Therapeutics: Department of Pharmacy Practice ## Pharmaceutical Sciences - **Diagram:** - Pharmaceutical Sciences contains the following branches: - Pharmacognosy - Pharmaceutics - Pharmaceutical Chemistry - Pharmacology - Pharmaceutics contains the following aspects: - Design of Dosage Forms - Manufacture of Dosage Forms - Evaluation of Dosage Forms - Biopharmaceutics is a separate branch that connects to Pharmaceutical Chemistry. - All of these branches come together while developing new drugs ## Introduction to Pharmaceutical Sciences ## Example 1: Aspirin - **3000-1500 BC:** Ancient Egyptians used willow bark as a remedy for aches and pains. - **~ 400 BC:** Hippocrates - willow bark useful as an antipyretic and analgesic. - **1763:** Reverend Stone publishes in the Royal Society detailing five years of experiments on using dried, powdered willow bark to cure fever. - **1826:** Sodium salicylate identified as active ingredient. - **1897-99:** Felix Hoffmann at Bayer acetylated Na salicylate. - **Acetyl salicylic acid = Aspirin**. - Bayer became synonymous with aspirin. ## Aspirin (continued) - Aspirin inhibits prostaglandin synthesis in human platelets. - Enteric-coated aspirin tablets. - Reduces pain, inflammation, risk of clots and stroke. ## Example 2: Digitalin - Extracted from the purple foxglove plant, used since medieval times for different therapies. - **1785:** William Withering first to describe use of its dried, powdered leaf for heart conditions in 163 patients. - Digitoxin and digoxin - drugs based on Digitalis extract. - **Active ingredient in the drugs is glycoside.** - Reversible inhibits ATPase, leads to increased intracellular sodium, causes calcium influx, increases heart contractility. - Given as oral solution, injectable solution, tablets. - **Not widely used due to very narrow Therapeutic Index (we will learn about this next class).** ## Example 3: Paclitaxel - **1960s:** Isolated from the bark of the Pacific yew tree. - **1971:** Chemical structure published. Molecular formula is C47H51NO14. Complex structure involving a tetracyclic "taxane" ring system. - Due to limited availability of the tree, synthetic methods of producing paclitaxel were then developed. - **1977-78:** Antitumor activity confirmed. Stabilizes microtubules and prevents their disassembly, inhibiting cell division. - Paclitaxel has poor solubility, it was encapsulated within a drug delivery vehicle Cremophor EL. - **1992:** Approved by US FDA, used to treat ovarian cancer. ## Research in the College of Pharmacy - Identifying new compounds with medicinal properties from natural sources. - Drs. Rowley, Seeram - Studying how DNA damage occurs and how this can lead to cancer initiation. - Dr. Cho - Designing dosage forms to deliver drugs to where they are needed in the body. - Drs. Chen, Menon, Shih - Studying drug PK and PD to develop personalized therapies. - Drs. Achour, Fischer - Looking at diseases, causative agents (e.g. bacteria) and drug mechanisms at the cellular and molecular level. - Drs. Slitt, Deng, King, Li, Ghonem, Clements - Neurodegeneration, nerve injuries, motor function, ageing. - Drs. Quinlan, Ross, Manuel, Fallini, Alber ## What was an important thing missing from early drug development/evaluations? - **Done before a treatment is approved for everyday use**. - **Studies to determine whether a new drug, treatment or combination works, and is safe for use in people.** - **Most costly aspect of drug development** ## Why is this important? - To check if drugs are SAFE - To check if drugs are EFFECTIVE - To check if the drug is better than standard treatment given for the disease. ## Importance of Clinical Evaluation - **Thalidomide:** - **1957:** Marketed as nonaddictive sedative. - **Was found to be effective in curing morning sickness in pregnant women.** - **1961:** Reports linking thalidomide use in pregnancy to severe birth defects. - **1962:** Banned in most countries where it was sold. - >10,000 children affected - 50% had serious limb deformities. - **Now we have regulations requiring extensive clinical studies to demonstrate safety as well as efficacy.** ## Introduction to Pharmaceutics - The DESIGN, MANUFACTURE and EVALUATION of DOSAGE FORMS ## What is a dosage form? - The physical system used to administer drugs. - **Solid oral dosage forms**: Tablets, Capsules given per os (by mouth). - **Semisolid dosage forms**: Ointments, Creams. - **Solutions**: IV injections, IM injections, syrups. - **Others**: Patches, suppositories, etc. ## DESIGN of dosage forms 1. Identify the active pharmaceutical ingredient (API). 2. Identify appropriate dosage form for the API: units that patients can conveniently take that will ensure that the active drug gets into the body and is delivered to its site of action. 3. Could be tablets, capsules, liquid preparations, transdermal, intranasal, etc. 4. Design the dosage forms, select appropriate size, shape, inert ingredients (excipients). 5. Create innovative dosage forms and ways to get drugs to the site of action – e.g. “targeting" specific cells, using magnet to guide the dosage forms to the disease site. ## MANUFACTURE of dosage forms - The series of steps involved in converting the raw materials into the final finished product. 1. Work out process to make them on a small scale. 2. Work out how to make them on a big scale (scale-up). ## EVALUATION of dosage forms - Steps followed to check the properties and specifications of the prepared pharmaceutical dosage form. Done to confirm quality of the final product. 1. General appearance – Size, shape, thickness. 2. Weight, content uniformity. 3. Stability (of drug and dosage form). 4. How much, and how quickly does drug get into the body. - And many more as we will see. ## Tablet -Compressed powder mass - **Zyrtec 10 mg (Johnson & Johnson) BRAND NAME:** - Are they hard enough to be handled without crumbling? - Not too brittle that they chip? - Not too hard that they don't release the drug? - What coating process to be used? - Will drug be stable under different storage conditions? - Will different batches of product behave the same? - **Cetirizine 10 mg (Mylan) GENERIC BRAND NAME:** - In addition to all the above requirements--- - Does this tablet yield or release the same amount of drug as Zyrtec ? - Does it release it at the same rate as Zyrtec? - Can it be substituted for Zyrtec? ## Introduction to Biopharmaceutics ## Pharmaceutical Sciences (Diagram) - Pharmaceutical Sciences contains the following branches: - Pharmacognosy - Pharmaceutics - Pharmaceutical Chemistry - Pharmacology - Pharmaceutics contains the following aspects: - Design of Dosage Forms - Manufacture of Dosage Forms - Evaluation of Dosage Forms - Biopharmaceutics is a separate branch that connects to Pharmaceutical Chemistry. - All of these branches come together while developing new drugs. ## Objectives of BPS 301 - Define biopharmaceutics. - Factors controlling rate and extent of drug absorption. - Routes of administration. - Types of dosage forms. - Nature of drug. - Components of the dosage forms (e.g. excipients). - Evaluation of bioavailability. - Factors controlling drug stability. - Regulations for drug approval and manufacture. ## Introduction to Drug, PK, PD - **Background:** - Drugs. - Pharmacodynamics (PD) and the therapeutic range. - Pharmacokinetics (PK) and the processes of ADME - To be covered in detail in the upcoming classes. ## Biopharmaceutics - Examines the relationship of the physical and chemical properties of the drug, the dosage form in which the drug is formulated and the route of administration for delivery of the drug to the site of action. ## Drugs - **What are drugs?** - By extension they must also possess the ability to do harm! - Too little, no effect. - Too much, adverse effects - continuation of therapeutic effect or could increase effect of another drug (e.g. digoxin vs quinidine). ## Drugs (Continued) - **Diagram:** - **Pre-1950s:** Drugs from natural sources. - **1950s:** "Small molecules"<300 Da MW (Some exceptions). - **1980s:** "Biologics" or "biotech drugs" - Large MW (proteins, antibodies) - Difficulty passing biological membranes - Often not po - Very different absorption, distribution and elimination properties - **2000s:** - Monoclonal antibodies - Targeted therapies - mRNAs - Personalized medicine ## Biologics - Medications obtained from biological sources. - Usually large, complex molecules. - Examples - Sugars, proteins, nucleic acids, antibodies. - Manufactured under precise conditions. - Herceptin – Treats breast cancer. - Humira - Treats rheumatoid arthritis. - Used to treat various indications insomnia, multiple sclerosis, severe pain, chronic kidney disease, incontinence, mouth sores, and cancer. - **Diagram:** - Comparing small molecule (Aspirin) and biologic molecules in terms of size and complexity. - **Size:** - Small molecules (Aspirin) have 21 atoms. - Biologics have 25,000 atoms. - **Complexity:** - Small molecules (Aspirin) have 150 parts. - Biologics have 4,000,000 parts. ## Types of biologics drugs/ treatments - **Diagram:** - Types of Biologics: - Antibodies - Hormones - Growth factors - Vaccines - Cytokines - Gene Therapy - Artificial cells, tissues/organs ## Biologics - **Diagram:** - Small Molecule Drug (Aspirin) with 21 atoms. - Small Biologic (Human Growth Hormone) with 3000 atoms. - Large Biologic (Monoclonal antibody) with 25,000 atoms. - Between 2012 and 2021, an average of 44 drugs per year were approved. - **Biosimilars** - A biologic drug/ product that is “highly similar” to another approved biologic and has no clinically meaningful differences. - The majority of this course will address small molecules and how they produce therapeutic response in the body. ## Who monitors drug safety and efficacy? - US Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER). - Does this in two phases: - **Preapproval**: Reviews manufacturers' applications to market drugs in the US. - **Postapproval**: Once a drug is on the market, FDA continues its oversight of drug safety and effectiveness. Done as long as the drug is on the market. ## How do we choose the optimal route, dose and dosing interval for a drug? - **Diagram:** - **INPUT:** - Route - Dose - Dose Frequency - Dosage form - **DRUG - BODY - OUTPUT:** - Response - Optimal dosage, route and dosing interval is one that maximizes the likelihood of a response while simultaneously minimizing likelihood of toxicity in the patient. ## Drug Response (Continued) - All these steps can be broken down into two phases: - **Pharmacokinetics (PK)**: Describes the movement of drug in the body. Studies the kinetics of drug absorption, distribution, and elimination (metabolism and excretion) - what the body does to the drug. - **Pharmacodynamics (PD)**: Studies the relationship between drug concentration at the site of action and the therapeutic effect (onset, duration and magnitude of response), and possible adverse events- what the drug does to the body. - PD is critical. All other processes feed into this. ## To summarize, - Today we discussed: - Definitions of Pharmacy, Pharmaceutical Sciences - Pharmaceutics and what is involved in the design, manufacture and evaluation of dosage forms - Definition of Biopharmaceutics - Small molecule drugs vs biologic drugs - Introduction to PK,PD