BIOPHAR - Biopharmaceutics and Its Role in Drug Development

BIOPHARMACEUTICS

• understanding the relationship between the biological aspects of a living organisms and the physical and chemical principles that govern the behavior of drugs or medicinal products

PHYSICAL PHARMACY

is a field that focuses on the application of basic chemistry concepts to understand how drugs behave and interact in the body

THERMODYNAMICS AND CHEMICAL KINETICS

two important branches of chemistry where physical pharmacy is based on

THERMODYNAMICS

• helps us understand the energy and heat flow in chemical systems
• helps explain how drugs dissolve, disperse, and distribute within the body
• it also sheds light on processes like drug stability and degradation

CHEMICAL KINETICS

• deals with the rate of chemical reactions
• helps us understand how drugs break down, are absorbed, metabolized, and eliminated in the body
• helps us determine the time it takes for a drug to have its desired effect or to be cleared from the system

SOLUBILITY

• is a measure of how much of a substance, like a drug can dissolve in a specific solvent
• one of the most important physical-chemical characteristics that scientists investigate when developing new drug candidates

KINETIC SOLUBILITY

• initial phase before a drug reaches its maximum solubility
• refers to the amount of the drug that dissolves over time before it reaches equilibrium (when no more drug can dissolve)

HYDROPHILICITY / LIPOPHILICITY

help us understand how a drug interacts with different types of solvents and biological systems

PARTITION OR DISTRIBUTION COEFFICIENT (log P / log D)

is a measure of a compound's tendency to move between hydrophilic (water-like) and lipophilic (fat-like) solvents

HIGH LOG P VALUE

it means it is more lipophilic and tends to dissolve better in fat-like solvents

LOW LOG P VALUE

it indicates a higher hydrophilicity, meaning it dissolves better in water-like solvents

LIPOPHILIC DRUGS

have an easier time crossing cell membranes 9important for their absorption into the bloodstream and their distribution throughout the body)

HYDROPHILIC DRUGS

may have more difficult crossing membranes and may require different delivery stretegies

SALT FORMS AND POLYMORPHS

• when it comes to drug susbstances, they can exist in various solid-state forms (each with its own characteristics)
• can significantly influence its properties (ex: solubility; may have diff solubilities = impact how quickly the drug is released and absorbed in the body)

DISSOLUTION RATE OF A DRUG

• how quickly it dissolves in a specific medium
• different forms may exhibit different dissolution rates, which can affect the drug's bioavailability and therapeutic effectiveness

STABILITY

• certain forms may be more stable or prone to degradation, affecting the shelf-life and effectiveness of the drug over time

HYGROSCOPICITY

refers to a substance's ability to absorb moisture from the environment (can impact the drug's stability and manufacturing processes)

MANUFACTURABILITY

different forms may require different manufacturing techniques or excipients to ensure the drug's proper formulation and delivery

CLINICAL PERFORMANCE

of the drug may influence factors such as the drug's absorption, distribution, metabolism, and elimination in the body (impact drug's therapeutic effectiveness and patient outcomes)

CHEMICAL STABILITY

is a critical aspect when it comes to drugs, as it ensures that the drug substance or drug product remains intact and does not degrade over time

SHELF-LIFE

• the chemical stability of the API directly impacts the __ of the drug product
• it refers to the length of time a drug product remains stable and maintains its desired quality under recommended storage conditions

pH-STABILITY PROFILE

• refers to how stable it is at different pH values
• important to understand how the material will behave within the body, especially in the gastrointestinal (GI) tract

PARTICLE SIZE

smaller ___ often lead to increased dissolution rates, which means the drug can dissolve more quickly in the body (can also affect the appearance, texture, and flow characteristics of powders)

DENSITY

• refers to how closely packed the particles are in a powder
• important in processes such as compression or filling into capsules
• affects the weight and volume of the drug product (also flowability and dosage accuracy0

FLOWABILITY

refers to how easily the powder flow, pours, or fills into different dosage forms, such as tablets or capsules

WETTABILITY

describes how well a powder can be wetted or dispersed in a liquid

SURFACE AREA

• is the total area of the particles exposed to the surrounding environment
• it influences the rate at which a drug can dissolve

IONIZATION

refers to the process in which a molecule gains or loses an electric charge by gaining or losing an electron

FORMULATION PRINCIPLES

• play a crucial role in biopharmaceutics, which focuses on optimizing the delivery and performance of active pharmaceutical ingredients (APIs) in the body
• it ensure its effective delivery to the target tissue through a specific route of administration
• essential in determining the biopharmaceutical profile of a compound
• closely linked to the pharmacokinetic behavior of the drug

SELECTION OF A DRUG CANDIDATE DURING THE PRECLINICAL DEVELOPMENT STAGE

• is a critical process that combines aspects of both drug discovery and drug development
• it involves identifying and evaluating compounds with the potential to become effective and safe drugs

DISCOVERY PHASE

• scientists work to synthesize and test candidate compounds that exhibit the desired activity and potency at the intended target
• safety profile (assess potential toxicity and side effects - preclinical studies)
• ADME properties of the compound

PHASE I CLINICAL STUDIES

involves conducting additional biopharmaceutical assessments to enhance the understanding of the drug candidate's properties and ensure its safety

ANIMAL SAFETY STUDIES

one of the key steps in phase I clinical studies

EARLY CLINICAL DEVELOPMENT

• several key goals are pursued to gather essential information about the drug candidate
• these goals include establishing safety, understanding PK, PD, and determining an effective dose range through single-dose and multiple-dose studies

RELATIVE BIOAVAILABILITY STUDY

this types of study is performed to compare the bioavailability of a drug product against different formulations or dosage forms

ABSOLUTE BIOAVAILABILITY STUDY

the goal is to determine the extent of drug absorption from a specific formulation by comparing it to an intravenous (IV) reference dose

BIOEQUIVALENCE

similarity; distinct type of BA with the objective of assessing stastistical similarity

ADVANCED STAGES OF CLINICAL DEVELOPMENT (PHASE II AND III)

• objective: undergo a shift from primarily assessing safety and pharmacokinetics (PK) to evaluating both safety and efficacy
• demonstrating that the formulations consistently and reliably produce the desired therapeutic effect in a large and diverse patient population