Biopharmaceutics and Drug Dosage Forms

Introduction to Biopharmaceutics and Drug Dosage Forms/Drug Databases

• Gretchen M. Ray, PharmD, PhC, BCACP, CDCES, Associate Professor, UNM College of Pharmacy, lectured on January 17, 2025.

Objectives

• Define biopharmaceutics.
• Explain the relationship between pharmaceutical equivalence, bioequivalence, and therapeutic equivalence, and how these relate to generic drugs.
• Identify important counseling points and prescribing considerations for various outpatient dosage forms, such as capsules, tablets, oral solutions, suspensions, elixirs, and transdermal preparations.
• Locate information about available dosage forms in a drug reference (such as Lexidrug™).
• Locate sections describing drug administration considerations.
• Locate sections describing ADME characteristics of a drug.
• Determine if it's safe to cut or crush a dosage form.

Supplemental Readings/References

• Shargel L, Yu AC. Applied Biopharmaceutics & Pharmacokinetics. 7th ed., 2016. Accessed: October 24, 2017, at http://accesspharmacy.mhmedical.com/content.aspx?bookid=1592&sectionid=100668900.
• Allen LV, Ansel HC. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems. 10th ed., 2014.

Biopharmaceutics

• The relationship between a drug's physical and chemical properties, dosage form, and route of administration affects the rate and extent of drug absorption.

• Key processes include drug release and dissolution, absorption, distribution, drug distribution in tissues, elimination, excretion, and metabolism.

• These processes influence the therapeutic or clinical effect.

• Factors affecting biopharmaceutics include: design of the drug dosage form, stability of the drug, and manufacture of the drug product, release of the drug from the drug product, and rate of dissolution of the drug at the absorption site.

• Influence therapeutic decisions in prescribing.

Generic Drug Approval

• Generic and brand-name drugs are not identical.
• A new drug application (NDA) approved by the FDA results in a patent.
• Generic companies can market generic versions when the patent expires.
• Generic products must contain the same active pharmaceutical ingredient, be the same dosage form, and use the same route of administration as the brand-name drug.
• ANDA approval requires the generic drug to be a therapeutic equivalent of the brand drug, proven to be safe and effective, and a pharmaceutical equivalent.
• A generic drug must contain similar amounts of chemically active ingredients but may contain different inactive ingredients (excipients).
• The rate and extent of active drug reaching the site of action must be the same as the branded drug (bioequivalence).

Routes of Administration and Associated Drug Dosage Forms

• Oral route (tablets, capsules, suspensions, solutions/elixirs, syrups) is the most frequent administration method, but absorption is slow, variable.
• Rectal route (suppositories) is useful when patients are vomiting or unconscious, approximately 50% bypass the liver, but absorption is irregular.
• Parental route (subcutaneous, intramuscular, intravenous, intradermal) is preferred for drugs destroyed by the GI tract. Absorption is rapid and predictable, but once administered, it is difficult to remove the drug in case of overdose. Sterility requirements and trained personnel needed.
• Epicutaneous route (lotions, creams, ointments, transdermal patches) involves topical application to the skin. Transdermal patches allow sustained systemic drug delivery. Ointments, lotions, and creams are for local action with minimal absorption.
• Ophthalmic, otic, and nasal routes are used for local action. Absorption can be minimal to systemic.

Modified Release Drug Products

• Most oral drugs are considered immediate release (IR).
• Modified release forms alter timing and/or rate of release, improving patient adherence and/or therapeutic effect. Examples include extended-release, delayed-release, enteric-coated tablets, repeat-action, targeted-release, and orally disintegrating tablets (ODTs).
• Modified-release drugs offer sustained therapeutic blood levels, improved patient adherence, improved tolerability, but may suffer from dose-dumping, less flexibility for dose adjustments, and may be more difficult for high doses due to the size of the product.

Clinical Considerations for Oral Modified Release Dosage Forms

• Do not switch back to immediate-release (IR) without considering existing blood concentrations of extended-release (ER) drugs.
• Instruct patients that modified-release tablets and capsules should not be crushed or chewed.
• Some non-erodible matrix shells and osmotic-release tablets may be visible in the stool, and empty shells or ghosts from osmotic tablets should be expected.
• Consult a drug reference if necessary.

Clinical Considerations When Prescribing Drug Patches

• Absorption from transdermal patches varies depending on application site; use package insert instructions.
• Apply patch to clean, dry skin without hair, or consider factors like wet/moist skin, lotion, etc, that may affect drug permeation.
• Do not cut the patch; remove the old patch before applying a new one.

Practice with Drug Database

• Open databases (such as Lexi-Comp) are helpful in checking drug information, searching drugs like amoxicillin (antibiotic), promethazine (anti-emetic), and discussing characteristics (ADME), dosage forms, preparations, administration, pharmacology/pharmacokinetics, pharmacodynamics/kinetics, and indications/contraindications.
• Use the database to determine if it's safe to cut pantoprazole tablets in half.