Pharmaceutics: Dosage Forms and Excipients

• Pharmaceutics is the pharmacy discipline focused on converting new chemical entities (NCEs) or existing drugs into safe and effective medications for patients.
• Pharmaceutics is also defined as the science of dosage form design.

Dosage Forms

• Dosage forms involve pharmaceutical products marketed for use, featuring a specific blend of active ingredients and inactive components (excipients).
• This mixture is presented in a particular configuration and divided into a unit dose.
• Dosage forms are categorized based on their physical state (solid, liquid, semi-solid), administration route (oral, topical, injectable), or release characteristics (immediate, modified).

Excipients

• Excipients are inactive ingredients included alongside the active pharmaceutical ingredient (API) in medications.
• Excipients enhance drug solubility, stability, bioavailability, and manufacturability.
• Common excipients include binders, fillers, disintegrants, lubricants, glidants, preservatives, and colorants.

Preformulation Studies

• Preformulation studies characterize a drug substance's physical, chemical, and mechanical properties to develop stable, safe, and effective dosage forms.
• Key preformulation parameters include solubility, partition coefficient, dissolution rate, polymorphism, hygroscopicity, and stability.
• Solubility is a drug substance's ability to dissolve in a solvent.
• Partition coefficient represents the ratio of a drug's concentration in two immiscible solvents, indicating its lipophilicity or hydrophilicity.
• Dissolution rate measures the speed at which a drug substance dissolves in a dissolution medium.
• Polymorphism is a drug substance's existence in different crystalline forms, impacting its physicochemical properties.
• Hygroscopicity is a drug substance's capacity to absorb moisture from the air.
• Stability is a drug substance's ability to maintain integrity and potency over time under defined storage conditions.

Solid Dosage Forms

• Solid dosage forms are the most prevalent type of pharmaceutical preparations.
• They offer ease of handling, accurate dosing, and good stability.
• Examples include tablets, capsules, powders, granules, and suppositories.

Tablets

• Tablets are solid dosage forms made by compression or molding, containing active ingredients and excipients.
• Tablet types include compressed, sugar-coated, film-coated, enteric-coated, chewable, and effervescent tablets.
• Tablet manufacturing uses wet granulation, dry granulation (slugging or roller compaction), and direct compression.

Capsules

• Capsules are solid dosage forms with the drug substance enclosed in a hard or soft soluble shell.
• Hard gelatin capsules have two halves (body and cap) filled with powder, granules, or pellets.
• Soft gelatin capsules are one-piece, hermetically sealed shells containing liquids, semi-solids, or solids.
• Capsule filling processes include powder, liquid, and pellet filling.

Liquid Dosage Forms

• Liquid dosage forms involve drug substances dissolved, suspended, or emulsified in a liquid vehicle.
• They offer easy swallowing, rapid absorption, and dosing flexibility.
• Examples include solutions, suspensions, emulsions, syrups, elixirs, and tinctures.

Solutions

• Solutions are liquid preparations with one or more drug substances dissolved in a solvent or solvent mixture.
• Solution types include oral, topical, otic, and ophthalmic solutions.
• Solution preparation involves dissolving the drug substance in the solvent, followed by filtration and packaging.

Suspensions

• Suspensions are liquid preparations containing finely divided, undissolved drug particles dispersed in a liquid vehicle.
• Suspension types include oral, topical, and injectable suspensions.
• Suspension preparation involves milling or micronizing the drug substance, dispersing it in the liquid vehicle using suspending agents, and stabilizing the suspension.

Emulsions

• Emulsions are liquid preparations of two immiscible liquids, one dispersed as globules within the other.
• Emulsion types include oil-in-water (O/W) and water-in-oil (W/O) emulsions.
• Emulsion preparation involves mixing the two immiscible liquids with emulsifying agents to reduce interfacial tension and stabilize the emulsion.

Semi-Solid Dosage Forms

• Semi-solid dosage forms have a consistency between solid and liquid.
• They are for topical or mucosal application.
• Examples include ointments, creams, gels, pastes, and suppositories.

Ointments

• Ointments are semi-solid preparations for external application to the skin or mucous membranes.
• They consist of a drug substance dissolved or dispersed in an ointment base like hydrocarbon, absorption, water-removable, or water-soluble bases.
• Ointment preparation involves incorporating the drug substance into the ointment base, followed by homogenization and packaging.

Creams

• Creams are semi-solid emulsions with drug substances dissolved or dispersed in either a W/O or O/W emulsion base.
• They are for external application to the skin or mucous membranes.
• Cream preparation involves preparing the emulsion base, incorporating the drug substance, and homogenizing the cream.

Gels

• Gels are semi-solid systems with a liquid phase entrapped in a three-dimensional polymeric matrix.
• They are clear or translucent and contain drug substances dissolved or dispersed in the liquid phase.
• Gel preparation involves dispersing or dissolving the gelling agent in the liquid phase, followed by hydration and cross-linking to form the gel structure.

Sterile Dosage Forms

• Sterile dosage forms are free from microorganisms.
• They are for administration by injection, infusion, or application to sterile body sites.
• Examples include injections, intravenous infusions, ophthalmic solutions, and irrigations.

Injections

• Injections are sterile solutions, suspensions, or emulsions for parenteral administration.
• They are packaged in ampules, vials, or prefilled syringes.
• Injection preparation involves dissolving or suspending the drug substance in a sterile vehicle, sterilizing by filtration or autoclaving, and aseptically filling the containers.

Pharmaceutical Manufacturing

• Pharmaceutical manufacturing is the large-scale production of drug products under strict quality control and regulatory guidelines.
• Key processes include blending, granulation, tableting, encapsulation, filling, sterilization, and packaging.
• Good Manufacturing Practices (GMP) ensure drug products are consistently produced and controlled to quality standards.
• GMP covers all manufacturing aspects, from raw materials and facilities to equipment and personnel training.

Drug Delivery Systems

• Drug delivery systems enhance therapeutic efficacy and safety by controlling drug release, absorption, distribution, and metabolism.
• Types include immediate-release, modified-release, targeted-release, and controlled-release systems.

Modified-Release Dosage Forms

• Modified-release dosage forms release the drug substance at a different rate or time than immediate-release forms.
• Types include extended-release, delayed-release, and repeat-action dosage forms.
• Extended-release dosage forms release the drug slowly over an extended period for prolonged therapeutic effect.
• Delayed-release dosage forms release the drug at a specific time or location, such as the colon.

Regulatory Considerations

• Pharmaceutical development and manufacturing are strictly regulated to ensure drug product safety, efficacy, and quality.
• Agencies like the FDA in the United States and the EMA in Europe set standards and guidelines for drug development, manufacturing, and marketing.
• A New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) must be submitted for approval to market a new drug product.