Routes of Administration - Study Guide

**Routes of Administration** Medicine = drug + excipients **Dose**: amount of a drug that is required to have a therapeutic effect with minimal unwanted effects - Different drugs have different doses - Dose of the same drug can be different depending on the formulation and indication **...

**Routes of Administration** Medicine = drug + excipients **Dose**: amount of a drug that is required to have a therapeutic effect with minimal unwanted effects - Different drugs have different doses - Dose of the same drug can be different depending on the formulation and indication **Formulation**: presentation of a drug in a manner in which it can be suitably administered to a patient to achieve a predictable and reproducible therapeutic response. - Easily administered - Convenient - Controlled therapeutic response **Route of administration** **Formulation** ----------------------------- -------------------------------------------------------------------------------------------- Oral tablets, capsules, granules, powders, solutions, syrups, suspensions, emulsions, gels, etc Rectal suppositories, creams, enemas, foams, etc Urethral solutions, etc Vaginal ointments, pessaries Topical (skin) ointments, creams, pastes, lotions, gels, solutions, topical aerosols, patches, etc Parenteral injections (solutions, suspensions, emulsions), implants, etc Pulmonary (respiratory) aerosols (solutions, suspensions, emulsions, powders), inhalations, etc Nasal (nose) solutions, inhalations, etc Ocular (eye) solutions, ointments, creams, inserts, lenses, etc Aural (ear) solutions, suspensions, ointments, creams, etc **Routes of administration -- Local and systemic** - Local -- drug acts locally in a target cell/tissue or organ - Systemic -- drug goes into the bloodstream and therefore goes everywhere in the body **Requirements of dosage forms** - Reproducible performance - Acceptable to patient - Large scale production - Reproduce quality (meet product/process performance objectives with minimal variation) - Physically and chemically stable - Preservation **Dosage form design** - A new drug substance - information to help design a dosage form - Therapeutic considerations - Drug factors (mainly physical properties) -- critical material attributes that affect manufacture and performance of dosage form e.g. particle size (dissolution, mixing, flow, drug often minor component) - Biopharmaceutical considerations (ADME) - Routes -- oral, rectal, topical, parenteral, respiratory, nasal, eye, ear,... **\ ** **Oral route** +-----------------------------------+-----------------------------------+ | **Advantages** | **Disadvantages** | +===================================+===================================+ | - Swallowing an immediate | - Lag time | | release tablet | | | | - Hostile environment (pH, | | - Most common & safe | enzymes) | | | | | - Modified release forms | - Variability -- chrono | | | pharmaceutics | | - High surface area | | | | - First-pass metabolism | | - Good blood supply | | | | - Difficult to reverse therapy | | | | | | - Irritation to | | | gastro-intestinal system | +-----------------------------------+-----------------------------------+ **First-pass metabolism or pre-systemic clearance** When a patient takes a drug orally, it goes to the small intestine which is the region where most nutrients and other materials are absorbed. The blood leaving the small intestine flows into the liver via hepatic portal vein which carries it to the systemic circulation. Thus, drugs which are metabolised by the liver are degraded before reaching systemic circulation. - **First-pass metabolism** -- when a drug is susceptible to first-pass metabolism, it may not be able to deliver it orally at all. Otherwise, dose adjustment is needed. +-----------------------------------+-----------------------------------+ | Solid dosage formulation | **Tablets** | | | | | | - Most commonly used | | | | | | - Accounts for 70% | | | | | | - Various shapes and sizes | | | | | | - Can be coated -- sugar coated | | | tablets, film-coated tablets | | | and enteric-coated | +===================================+===================================+ | | **Capsules** | | | | | | - Drug enclosed in a small | | | gelatine shell | | | | | | - Can be "hard" or "soft" | | | | | | - Hard gelatine is most | | | commonly used | | | | | | - Soft gelatine used for | | | encapsulating liquids | | | | | | - Useful for drugs that are | | | poorly released from tablets, | | | and mask taste/smell | +-----------------------------------+-----------------------------------+ | Liquid dosage formulation | **Solutions** | | | | | | - Homogenous one-phase system | | | containing two or more | | | components | | | | | | - Drug dissolved in a solvent, | | | usually water | | | | | | - Greater absorption and | | | bioavailability | +-----------------------------------+-----------------------------------+ | | **Suspensions** | | | | | | - Insoluble drug suspended in a | | | suitable vehicle | +-----------------------------------+-----------------------------------+ | | **Emulsions** | | | | | | - Two immiscible liquids, one | | | finely divided distributed in | | | another | | | | | | - Mixture of aqueous and oily | | | phase | +-----------------------------------+-----------------------------------+ **Parenteral route** ; Injected into body Three main routes -- subcutaneous, intramuscular, intravenous - Rabid onset - Drug enters general circulation without hepatic passage -- no first-pass metabolism - Better bioavailability for hydrophilic drugs - Sterile environment - Phobia - Reverse therapy? **Topical route** - Applied to skin - Local conditions and systemic - Limited s/e - Poor absorption **Formulation** -- creams, ointments, gels, patches **Rectal route** - Rectal suppository (less liquid -- absorption ↓) - Local use and systemic delivery - Used for drugs inactivated in GIT - Alternative to the oral route - Avoid first-pass metabolism - Erratic absorption **Respiratory route** - Local effect - Delivered in gaseous, mist form - Minimal s/e - Drug deposition - Drug particle size **Formulation** -- Need to use inhaler devices to deliver drugs: - Pressurised metered-dose inhaler (pMDI) - Dry powder inhaler (single & multiple) (DPI) - Nebulizer **Choice of routes** The route of administration is determined by the: - Physical characteristics of the drug - Rate which the drug is absorbed and/or released - Need to bypass hepatic metabolism and achieve high concentrations at particular sites - No single method of drug administration is ideal for all drugs in all circumstances