Pharmaceutics: Dosage Form Design

• Pharmaceutics is the science of dosage form design.
• It involves converting a drug substance into a medication suitable for use by patients.

Key Areas in Pharmaceutics

• Drug delivery: Designing how drugs are introduced into the body.
• Dosage form design: Creating the physical form of a medication.
• Drug absorption, distribution, metabolism, and excretion (ADME): Understanding how the body processes a drug.
• Formulation: The process of combining different ingredients to produce a final medicinal product.

Dosage Forms

• Dosage forms are the means by which drug molecules are delivered to sites of action within the body.
• Common dosage forms include tablets, capsules, creams, ointments, solutions, and injections.
• The choice of dosage form depends on factors such as the drug's properties, the route of administration, and patient needs.

Routes of Administration

• Enteral: Oral, sublingual, buccal, and rectal.
  • Oral route is the most common, involving swallowing a drug.
  • Sublingual and buccal routes involve placing the drug under the tongue or between the cheek and gum, respectively, for absorption into the bloodstream.
  • Rectal route involves inserting the drug into the rectum.
• Parenteral: Intravenous, intramuscular, subcutaneous.
  • Intravenous (IV) involves injecting the drug directly into a vein for rapid absorption.
  • Intramuscular (IM) involves injecting the drug into a muscle.
  • Subcutaneous (SC) involves injecting the drug under the skin.
• Topical: Application to the skin or mucous membranes.
  • Includes creams, ointments, lotions, and transdermal patches.
• Inhalation: Administration through the respiratory tract.
  • Includes inhalers and nebulizers.

Formulation

• Formulation involves selecting appropriate ingredients and processes to create a stable and effective dosage form.
• Excipients: Inactive ingredients added to the drug formulation to improve its properties.
  • Binders: Hold the ingredients in a tablet together.
  • Diluents: Increase the bulk of a tablet or capsule.
  • Disintegrants: Help a tablet break apart in the body.
  • Lubricants: Prevent ingredients from sticking to manufacturing equipment.
  • Coatings: Protect the drug from the environment and/or control its release.
• Manufacturing processes: Techniques used to produce dosage forms.
  • Granulation: Process of forming granules from powder particles.
  • Compression: Pressing granules into tablets.
  • Encapsulation: Filling capsules with powder or granules.
  • Sterile manufacturing: Producing sterile products for injection or ophthalmic use.

Drug Delivery Systems

• Conventional drug delivery: Immediate-release formulations that release the drug quickly into the body.
• Modified-release drug delivery: Formulations designed to control the rate or timing of drug release.
  • Extended-release: Releases the drug slowly over a prolonged period.
  • Delayed-release: Releases the drug at a specific time or location in the body.
  • Targeted-release: Delivers the drug directly to the site of action.
• Novel drug delivery systems: Advanced technologies for drug delivery.
  • Liposomes: Tiny vesicles used to encapsulate and deliver drugs.
  • Nanoparticles: Microscopic particles used to deliver drugs to specific cells or tissues.
  • Implants: Devices inserted into the body to release drugs over an extended period.

Biopharmaceutics

• Biopharmaceutics examines the factors influencing the bioavailability of a drug.
• Bioavailability: The rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action.
• Key factors affecting bioavailability:
  • Drug solubility: The ability of a drug to dissolve in a solvent.
  • Drug permeability: The ability of a drug to pass through biological membranes.
  • First-pass metabolism: The metabolism of a drug by the liver before it reaches systemic circulation.
  • Gastric emptying rate: The rate at which the stomach empties its contents into the small intestine.
  • Intestinal motility: The movement of the intestines.

Pharmacokinetics

• Pharmacokinetics describes the movement of drugs within the body.
• ADME processes:
  • Absorption: The process by which a drug enters the bloodstream.
  • Distribution: The process by which a drug spreads throughout the body.
  • Metabolism: The process by which the body breaks down a drug.
  • Excretion: The process by which the body eliminates a drug.
• Key pharmacokinetic parameters:
  • Area under the curve (AUC): A measure of the total drug exposure over time.
  • Maximum concentration (Cmax): The highest concentration of a drug in the body after administration.
  • Time to maximum concentration (Tmax): The time it takes for a drug to reach its maximum concentration in the body.
  • Half-life (t1/2): The time it takes for the concentration of a drug in the body to decrease by half.
  • Clearance (CL): The rate at which a drug is removed from the body.
  • Volume of distribution (Vd): A measure of the extent to which a drug distributes throughout the body.

Stability

• Drug stability refers to the extent to which a pharmaceutical product retains the same properties and characteristics.
• Chemical stability: Maintaining its chemical integrity and potency.
• Physical stability: Maintaining its physical appearance, palatability, uniformity, dissolution, and suspendability.
• Microbiological stability: Resistance to microbial growth and contamination.
• Factors affecting stability:
  • Temperature: High temperatures can accelerate degradation reactions.
  • Humidity: Moisture can promote hydrolysis and other degradation reactions.
  • Light: Exposure to light can cause photodegradation.
  • pH: Extreme pH values can cause degradation.
  • Oxygen: Oxidation can degrade certain drugs.

Regulatory Aspects

• Pharmaceutical products are regulated by government agencies to ensure their safety, efficacy, and quality.
• In the United States, the Food and Drug Administration (FDA) regulates pharmaceutical products.
• Good Manufacturing Practices (GMP): A set of guidelines that ensure pharmaceutical products are consistently produced and controlled according to quality standards.
• New Drug Application (NDA): An application submitted to the FDA to approve a new drug for sale.
• Abbreviated New Drug Application (ANDA): An application submitted to the FDA to approve a generic drug.

Compounding

• Compounding is the process of preparing medications by a pharmacist to meet the unique needs of a patient.
• Compounded medications are not FDA-approved and are not subject to the same manufacturing standards as commercially available drugs.
• Compounding pharmacies must follow specific regulations and guidelines to ensure the safety and quality of compounded medications.

Scale-Up and Manufacturing

• Scale-up is the process of increasing the production of a drug product from a small-scale laboratory setting to a large-scale manufacturing facility.
• Manufacturing considerations:
  • Equipment: Selecting appropriate equipment for large-scale production.
  • Process validation: Ensuring that the manufacturing process consistently produces a product of the required quality.
  • Quality control: Implementing procedures to monitor and control the quality of the product throughout the manufacturing process.
  • Packaging: Selecting appropriate packaging materials to protect the product from the environment.