Pharmaceutical Sciences Overview

Introduction to Biopharmaceutics and Drug Dosage Forms/Databases

• The presentation introduces biopharmaceutics and drug databases.
• A presenter, Gretchen M. Ray, PharmD, PhC, BCACP, CDCES, Associate Professor at UNM College of Pharmacy, led the session.
• The date of presentation: January 17, 2025.

Objectives

• Define biopharmaceutics.
• Explain pharmaceutical equivalence, bioequivalence, and therapeutic equivalence in relation to generic drugs.
• Identify factors relating to counseling and prescribing various outpatient dosage forms (capsules/tablets, solutions/suspensions/elixirs, and transdermal preparations).
• Locate drug administration considerations, dosage forms, and ADME characteristics in a drug reference (like Lexidrug).
• Determine if it is safe to cut or crush a dosage form.

Supplemental Readings/References

• Shargel L, Yu AC. Applied Biopharmaceutics & Pharmacokinetics, 7th edition (2016). Accessed: October 24, 2017.
• Allen LV, Ansel HC. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 10th edition (2014).

Biopharmaceutics

• Biopharmaceutics explores the connection between a drug's physical and chemical properties, dosage form, and administration route on the rate and extent of drug absorption.
• Key phases covered include drug release/dissolution, absorption, distribution, elimination, excretion, and metabolism and the eventual pharmacologic or clinical effect.

Biopharmaceutics (cont'd)

• Key elements include the design of the drug dosage form, stability of the drug product, manufacture of the drug product, release of the drug from the product, rate of dissolution at the absorption site, and delivery of the drug to its site of action.

Generic Drug Approval

• Generic and brand-name drugs are not always identical.
• Once the FDA approves a new drug application (NDA), a patent is granted.
• When the patent expires, other companies can produce generic versions of the drug.
• Generic drug products need to follow strict parameters.
• They must contain the same active pharmaceutical ingredient, same dosage form, and same route of administration as the brand-name drug.
• Abbreviated New Drug Applications (ANDAs) are used for generic drug approvals.

Generic Drug Approval (cont'd)

• ANDA approvals require the generic drug to be therapeutically equivalent to the brand drug.
• The generic drug must be proven safe and effective.
• The generic drug must be pharmaceutically equivalent to the brand drug.
• Dosage forms containing the identical amount of the chemically active pharmaceutical ingredient and may contain different inactive ingredients (excipients) (like color or preservatives).
• Generics are bioequivalent to the brand-name drug, and have the same rate and extent of active drug reaching the site of action.

Routes of Administration and Associated Drug Dosage Forms

• Oral route is the most common.
• Oral dosage forms include tablets, capsules, suspensions, solutions, and elixirs.
• Other methods for delivery include rectal, parental, topical, and ocular, otic, or nasal.
• Each route has its own benefits, disadvantages, and considerations.

Oral Route/Oral Dosage Forms

• Tablets are compressed solid dosage forms.
• Capsules contain a drug and filler, in a hard or soft gelatin shell.
• Suspensions contain insoluble drug particles in an aqueous vehicle.
• Most require shaking before administration.
• Solutions contain soluble drug particles in an aqueous vehicle.
• Elixirs are solutions in a hydroalcoholic vehicle.
• Syrups use sucrose as base.

Rectal Route

• Useful if patients cannot swallow.
• About 50% of absorbed drug bypasses the liver via the rectal route.
• Absorption is irregular and unpredictable.
• Suppositories are solid dosage forms that melt/dissolve to release the medicine.

Parental Route

• Drugs administered by injection.
• Drugs that are rapidly destroyed by the GI tract, require rapid absorption, or have predictable levels are given with this route.
• Disadvantage: difficult to remove drug in case of overdose, and sterility is crucial.
• Subcutaneous, intramuscular, intravenous, and intradermal are types of parental injection.

Topical Route

• Applied to the skin for local or systemic effects.
• Transdermal patches are a form designed for systemic absorption, often for slow release.
• Other topical forms are for local action with limited absorption (e.g., lotions, creams, ointments).

Ocular, Otic, and Nasal Routes

• Used to deliver drugs to the eyes, ears, and nasal passages.

Modified Release Drug Products

• Modified-release (MR) forms alter the timing or rate of drug delivery.
• This leads to improved patient adherence, dosage frequency, and systemic absorption control.
• Extended-release, delayed-release, enteric-coated, repeat-action, and targeted-release are examples.
• Orally disintegrating tablets (ODTs) disintegrate quickly without water.

Modified Release Drugs (cont'd)

• Advantages include sustained therapeutic blood levels, improved patient adherence, and improved tolerability.
• Disadvantages involve dose-dumping, less flexibility in dose adjustment, and high dose difficulty administration due to size.

Clinical Considerations for Oral Modified Release Dosage Forms

• Don't switch to immediate-release (IR) without considering existing blood concentration.
• Tablets and capsules should not be crushed or chewed.
• Non-erodible plastic matrix shells and osmotic tablets typically remain intact in stool.
• Contact drug resources if unsure regarding dosage form or application technique.

Modified Release Via Transdermal Drug Delivery Systems

• Allow passage of drugs from skin's surface into systemic circulation.
• Advantages include avoiding first-pass liver metabolism.
• Rapid drug termination by removing the patch.
• Disadvantages include potential for contact dermatitis, delayed onset, and difficulties administering high doses.

Clinical Considerations When Prescribing Drug Patches

• Confirm proper application site.
• Apply to clean, dry skin.
• Avoid lotions, and wet or moist skin.
• Patients should remove old patches before applying a new one.
• Discard the adhesive layer after use (safety considerations).

Practice with Drug Database

• Use of a drug database, like Lexi-Comp, was highlighted.

Lexi-Comp Introduction

• Lexi-comp is an open database.
• Search examples provided include Amoxicillin (antibiotic), Promethazine (anti-emetic), and Pantoprazole (proton pump inhibitor).
• ADME, dosage form, administration details, and clinical considerations are readily available for review using the database.