Pharmaceutics: Dosage Form Design and Drug Delivery

• Pharmaceutics is the science of dosage form design.
• It involves converting a new chemical entity (NCE) or an old drug into a medication to be used safely and effectively by patients.
• It also deals with the formulation, manufacturing, stability, and effectiveness of pharmaceutical dosage forms.

Key Areas in Pharmaceutics

• Drug Delivery: Focuses on how drugs are introduced into the body, including rates of absorption, distribution, metabolism, and excretion.
• Dosage Form Design: Designing pharmaceutical products to ensure they are both effective and safe for patient use.
• Biopharmaceutics: Studies the factors influencing the bioavailability of a drug in humans or animals and uses this information to optimize a drug product's therapeutic efficacy.
• Pharmacokinetics: Examines what the body does to a drug (absorption, distribution, metabolism, excretion).
• Pharmacodynamics: Examines what the drug does to the body, involving the drug's mechanism of action and its biochemical and physiological effects.

Drug Delivery Systems

• Immediate Release: Designed to release the drug immediately after administration.
• Modified Release: Includes extended-release, delayed-release, and targeted-release systems.
• Extended-Release: Allows a reduction in dosing frequency compared to immediate-release formulations.
• Delayed-Release: Releases the drug at a time other than immediately following administration.
• Targeted-Release: Delivers the drug to a specific site in the body.

Dosage Forms

• Solid Dosage Forms: Include tablets, capsules, powders, granules, and suppositories.
• Tablets: Solid preparations usually prepared by compressing powders or granules.
  • Can be formulated for immediate-release or modified-release.
  • Different types of tablets include compressed tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, and effervescent tablets.
• Capsules: Solid dosage forms in which the drug is enclosed within a hard or soft soluble container or shell.
  • Hard gelatin capsules typically contain dry, powdered ingredients or miniature pellets.
  • Soft gelatin capsules are used for oils and drugs that are dissolved or suspended in oil.
• Powders: A mixture of finely divided drugs or chemicals in a dry form.
• Granules: Prepared agglomerates of powdered materials, which may be used for tablets or capsules.
• Semisolid Dosage Forms: Include ointments, creams, gels, and pastes.
• Ointments: Semisolid preparations intended for external application to the skin or mucous membranes.
  • Usually contain less water and are more greasy than creams.
• Creams: Semisolid emulsions, usually containing more than 20% water and volatiles and/or less than 50% hydrocarbons, waxes, or polyethylene glycols.
• Gels: Semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle rendered jelly-like by the addition of a gelling agent.
• Pastes: Semisolid dosage forms that contain a high proportion of solid ingredients.
• Liquid Dosage Forms: Include solutions, suspensions, emulsions, syrups, elixirs, and injections.
• Solutions: Liquid preparations that contain one or more dissolved drugs in a suitable solvent.
• Suspensions: Liquid preparations consisting of solid particles dispersed throughout a liquid vehicle.
• Emulsions: A dispersion of one liquid in another immiscible liquid, stabilized by an emulsifying agent.
• Syrups: Concentrated aqueous solutions of a sugar, usually sucrose.
• Elixirs: Clear, sweetened hydroalcoholic liquids intended for oral use.
• Injections: Sterile, pyrogen-free preparations intended for parenteral administration.

Biopharmaceutics

• Absorption: The process by which a drug enters the bloodstream from its site of administration.
  • Influenced by factors like drug solubility, particle size, dosage form, route of administration, and physiological factors.
• Distribution: The process by which a drug is transported throughout the body to various tissues and organs.
  • Affected by factors such as blood flow, tissue permeability, and binding to plasma proteins.
• Metabolism: The process by which the body chemically modifies a drug, usually to make it more water-soluble for excretion.
  • Primarily occurs in the liver, but can also occur in other tissues.
• Excretion: The process by which the body eliminates a drug and its metabolites.
  • Primarily occurs through the kidneys (in urine), but can also occur through the liver (in bile), lungs (in exhaled air), and other routes.
• Bioavailability: The fraction of an administered dose of unchanged drug that reaches the systemic circulation.
  • Influenced by drug properties, dosage form, and route of administration.
• Bioequivalence: The comparison of bioavailability between different formulations of the same drug.

Pharmaceutical Manufacturing

• Formulation: The process of developing a dosage form that is both safe and effective.
  • Includes selecting appropriate excipients (inactive ingredients), determining the optimal drug concentration, and designing the manufacturing process.
• Mixing and Blending: Combining different ingredients to achieve a homogenous mixture.
• Particle Size Reduction: Reducing the particle size of drug substances to improve dissolution and bioavailability.
  • Techniques include milling and micronization.
• Granulation: The process of aggregating powder particles into larger, more uniform granules.
  • Improves flow properties and compressibility for tablet manufacturing.
• Drying: Removing moisture from granules or powders to improve stability and flow.
• Tablet Compression: Compressing granules or powders into tablets using specialized equipment.
• Coating: Applying a thin layer of material to the surface of a tablet or capsule for various purposes, such as masking taste, protecting the drug, or controlling drug release.
• Sterilization: Eliminating microorganisms from pharmaceutical products and equipment.
  • Methods include autoclaving, filtration, and radiation.

Stability

• Chemical Stability: The extent to which a drug retains its chemical integrity and potency over time.
• Physical Stability: The extent to which a dosage form retains its physical properties (e.g., appearance, hardness, dissolution rate) over time.
• Microbiological Stability: The extent to which a dosage form resists microbial contamination and growth.
• Factors Affecting Stability: Temperature, humidity, light, pH, oxygen, and interactions with excipients.
• Shelf Life: The period during which a drug product is expected to remain within its specifications if stored under recommended conditions.

Physicochemical Properties of Drugs

• Solubility: The ability of a drug to dissolve in a solvent.
  • Impacts absorption and bioavailability.
• Dissolution: The process by which a solid drug dissolves in a liquid.
  • A critical step for oral absorption.
• Partition Coefficient: A measure of a drug's relative affinity for two immiscible solvents (e.g., water and oil).
  • Influences drug distribution and permeation through biological membranes.
• pKa: The pH at which a drug is 50% ionized and 50% unionized.
  • Affects drug solubility and absorption.
• Polymorphism: The ability of a drug to exist in different crystalline forms.
  • Different polymorphs can have different physical properties (e.g., solubility, dissolution rate).

Regulatory Aspects

• Good Manufacturing Practices (GMP): A set of guidelines that ensure pharmaceutical products are consistently produced and controlled according to quality standards.
• Food and Drug Administration (FDA): The regulatory agency responsible for approving and regulating drugs in the United States.
• Investigational New Drug (IND) Application: An application submitted to the FDA to request permission to begin clinical trials on a new drug.
• New Drug Application (NDA): An application submitted to the FDA to request approval to market a new drug.
• Abbreviated New Drug Application (ANDA): An application submitted to the FDA for approval to market a generic drug product.