Dosage Forms

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Drug

An agent intended for use in diagnosis, mitigation, treatment, cure, or prevention of a disease.

Excipients

Inactive ingredients used in the preparation of dosage forms.

Formulation

The process in which different chemical substances (like active drug) are combined to produce a final drug product.

Drug Product

A specific combination of an active pharmaceutical ingredient and generally (but not necessarily) other inactive ingredients.

Dosage form

The form in which a drug is made and used (tablet, capsule, solution) with a specific combination of active ingredients and inactive components.

Drug Substance (Active Pharmaceutical Ingredient)

Material that exerts the pharmacological action. Used to make the drug product with excipients and inactive ingredients.

Impurity

Any component present in the excipient, drug substance, or drug product that is not desired, product-related, or excipient.

Prescription Drug

A human drug that is not safe for use except under the supervision of a licensed medical practicioner.

Gene Sequencing

Building a library of gene/protein sequences to mine for information.

Target discovery

Identifies a biological target (protein, enzyme, receptor, gene) involved in a disease.

Lead discovery

Find compounds that can combat/inhibit the biological target.

Natural Compound Screening

Testing compounds of natural origin for biologic activity. Uses in vitro cell culture models or enzyme systems for texting; slow and tedious process.

Screening Corporate compound collections

Testing several thousand molecules at once; ~15,000 compounds/week, 10-20 biological assays, relatively fast process.

In Silico Screening

3D structure of a target used for screening, In Silico tools simulate binding of candidate molecules to target

Rational Drug Design

Requires the knowledge of the 3D structure of the target active site; uses computer graphics to design a drug with a specific structure to bind to active site.

Combinatorial Chemistry

Preparation of a large number of different compounds by combining different chemical building blocks with each other.

ADMET

Describes ideal properties of drugs. Absorption, distribution, metabolism, excretion, toxicity.

CDER

Center for Drug Evaluation and Research; approves small-molecule drugs and differentiates OTC vs prescription status.

CBER

Center for Biologics Evaluation and Research; approves biologics drugs.

Pre-Clinical Phase

Proves a drug is safe and effective in animals; tests pharmacology, drug metabolism, and toxicology.

IND

Investigation New Drug; FDA reviews all preclinical testing and plans for clinical testing to determine if the drug is safe to move to human trials.

Phase I Clinical Trials

Tests safety in 20–100 healthy volunteers, starting with low doses and monitoring absorption, metabolism, and side effects as the dose increases.

Phase II Clinical Trials

Assesses effectiveness in 100-1000 health-impaired patients by testing dose range, how well it treats the disease, and short-term side effects.

Phase III Clinical Trials

Tests benefit/risk relationship of drug in 300-3000 health-impaired patients and less common/long-term side effects, along with labeling information.

NDA

Submitted to the FDA after successful clinical trials to get permission to market and sell the drug in the US if its safe and effective.

Phase IV Post Marketing Surveillance

Contribute to understanding of the drug’s mechanism, possible new therapeutic uses, additional side effects, and drug interactions.

Pre-Formulation

The physiochemical characterization of an active pharmaceutical ingredient.

Solubility

It is a measure of the maximum amount of substance that will dissolve in a liquid. Affected by pH, temperature, and particle size.

Partition Coefficient

Gives a measure of a drug’s preference of an oil/fat environment vs. water. The higher the partition coefficient, the grater the rate of transfer across the membrane.

Drug Permeability

Drugs must penetrate biological membranes by passive diffusion or specialized transport mechanism. Passive diffusion depends on the ratio of its water to lipid solubility.

Dissolution Rate

Time required for the drug to dissolve. Dissolution rate for poorly soluble drugs may often be due to the rate limiting step.

Polymorphism

The property of having more than one crystalline form and/or amorphous form. Polymorphs have different physical properties.

Crystalline

Uniform, highly ordered and well-defined arrangement of atoms to give a definite lattice structure.

Amorphous

Random, loose arrangement of atoms, molecules, and/or ions lacking a long range ordered structure.

Dissociation Constant

Measure of extent of ionization of the drug, ionization of a drug has a strong effect on its absorption, distribution, and elimination.

Particle Size

Particle size and size distribution are important because of the inverse relationship between particle size and surface area.

Particle Shape

Affects the flow and packing properties of powder. The more asymmetric a particle, the greater the surface area per unit volume.

Stability studies

The physical, chemical, and biological stability of a drug at its pure state and in the presence of excipients.

Solvents for Soln

Dissolve the drug substance

Flavors and Sweeteners for Soln

To make the product more palatable

Colorants for Soln

To enhance product appeal

Preservatives for Soln

Prevent microbial growth

Stabilizers for Soln

Prevent drug decomposition

Diluents or fillers for Tab

Increase the bulk of the formulation

Binders for Tab

Cause the adhesion of the powdered drug and pharmaceutical ingredients

Lubricants for Tab

Assist the smoothening of the tableting process

Disintegrating agents for Tab

Promote tablet break-up after administration

Passive Diffusion

Movement of molecules from high concentration to low concentration due to random molecular motion. No energy needed.

Fick’s First Law of Diffusion

The rate of diffusion is proportional to the different in drug concentration on both sides of the membrane. The bigger the difference in concentration, the faster molecules diffuse from high → low concentration.

Salt forms

Dissolve more readily than free acids or bases (ionized → polar)

State of hydration

Anhydrous forms are more readily soluble than hydrated forms.

Complex Formation

Formation of less soluble complexes results in reduced absorption.

Adsorption

Adhesion to the outside surface → reduced availability for absorption

Gastric emptying rate

Speed at which foods and liquids move through the stomach to the intestine. Rapid on an empty stomach

GI Tract Transit Time

The rate at which food moves from the mouth to rectum. Depends on the food you eat

Co-administration of other drugs

Drugs can affect absorption of other drugs

Age of the patient

Most physiological functions are decreased

Food taken by the patient

Most drugs are absorbed better with foods and liquids

Disease state of pt

Affects absorption. (GI tract motility is can slow down, absorption is slowed)

Biopharmaceutics Classification System

Groups drug substances based on their solubility and permeability.

Class I

High solubility, high permeability

Class II

Low solubility, high permeability

Class III

High solubility, low permeability

Class IV

Low solubility, low permeability

Bioavailability

The rate and extent to which an active drug ingredient is absorbed from a drug product and becomes available at the site of drug action.

Bioequivalence

The comparison of bioavailabilities of different formulations, drug productions, or batches of the same product

Therapeutic window

Between minimum toxic concentration and minimum effective concentration

Proprietary Drug Products

Brand name; a trademark officially registered by a company.

Non-proprietary drug products

Generic drugs; the generally recognized or common name for a drug in the drug product.

Generic Drug Product

A pharmaceutical product that can substitute a brand product as long as it’s bioequivalent, has the same active ingredient and strength, and same dosage form.

Pharmaceutical Equivalent

Drug products with the same active ingredient, strength, dosage form, and route of administration. May differ in shape, drug release mechanism, or inactive ingredients.

Pharmaceutical alternatives

Contain identical therapeutic moiety but not necessarily in the same amount or dosage form or as the same salt or ester.

Bioequivalent Drug Products

Pharmaceutical equivalents or alternatives whose rate and extent of absorption are similar when given at the same molar dose under similar conditions.

Therapeutic Equivalents

Drug products that are pharmaceutically equivalent and bioequivalent, so they’re expected to have the same clinical effect and safety when used as directed.

Noyes-Whitney Equation

Dissolution is faster when the drug has higher surface area and the concentration difference between the particle’s surface and the surrounding liquid is larger.

Route of Administration

The path by which a drug, fluid, poison, or other substance is brought into contact with the body.

First Pass Effect

The pharmacological agent is metabolized first when it is absorbed from the gut and delivered to the liver before it reaches the rest of the body.

Enteral Route

Any form of administration that involves any part of the gastrointestinal tract.

Oral Route

Most common ROA; given through oral cavity, absorption of drug may take place at any point along the GI tract.

Oral Route Advantages

Convenient, relatively safe, economical, natural, no need for sterilization.

Oral Route Disadvantages

Absorption can be variable, irritation, first-pass effect, too slow for emergency, can’t be given to unconscious patients.

Sublingual

Drugs are taken as smaller tablets which are held in the mouth under the tongue. Drug dissolves rapidly and provide rapid drug effects.

Buccal

Tablets designed for attaching to the buccal pouch for release of drugs over long periods and absorption through the oral mucosa.

SL/BL Route Advantages

Rapid absorption, drug stability, avoids first-pass effect, can be self-administered.

SL/BL Route Disadvantages

Inconvenient, small doses only, some may be swallowed by accident, few drugs are absorbed.

Rectal Route

Uses the rectum as a ROA for local and systemic effects of medication and other fluids. Local and systemic effects.

Rectal Route Advantages

Reduced first-pass metabolism, useful in children, elderly, or unconscious, higher drug concentrations can be achieved.

Rectal Route Disadvantages

Irritation or inflammation of rectal mucosa, absorption is slow and erratic, patient inconvenience.

Mucosal Route

Drug delivered via the absorptive mucosa in various easily accessible body cavities. Bucal, SL, and rectal → systemic, pulmonary, ocular, vaginal → local.

Mucosal Route Advantages

Rapid onset of action, avoids first-pass effect, suitable for acid labile drugs.

Mucosal Route Disadvantages

Not as convenient as oral route.

Parenteral Route

Medication given by injection or infusion, bypassing the gastrointestinal tract.

Intravascular (IV, IA)

Placing a drug directly into the blood stream.

Intramuscular (IM)

Drug injected deep into the skeletal muscle (~5mL)

Subcutaneous

Absorption of drugs from the subcutaneous tissues (~2mL)

Intradermal

Drug injected into the dermis of the skin (~0.1mL)

Intrathecal Injection

Injection into the spinal canal, or into the subarachnoid space so that it reaches the CSF.

Parenteral Route Advantages

Rapid onset, continuous titration, accurate dose, larger volume over longer period of time.

Parenteral Route Disadvantages

Dangerous due to rapid onset, overdose, sterile preparation and aseptic technique required.

Topical Route

Drug administered for local action of the drug, applied on the skin.