Pharmaceutical Equivalence and Generic Drugs

Introduction to Biopharmaceutics and Drug Dosage Forms/Databases

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

Objectives

• Define biopharmaceutics.
• Explain the link between pharmaceutical equivalence, bioequivalence, and therapeutic equivalence, especially regarding generic drugs.
• Recognize important counseling points and considerations for various outpatient dosage forms (e.g., capsules, tablets, oral solutions, transdermal preparations).
• Locate sections on available dosage forms, administration, and ADME (Absorption, Distribution, Metabolism, Excretion) characteristics of a drug within a drug reference (using Lexidrug™ as an example).
• Determine if it's safe to cut or crush a dosage form.

Supplemental Readings/References

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

Biopharmaceutics

• The relationship between a drug's physical and chemical properties, dosage form, and route of administration affects the rate and extent of its absorption.
• This includes drug release and dissolution processes, drug distribution in the systemic circulation and tissues, and drug elimination (excretion and metabolism) leading to a pharmacologic or clinical effect.

Biopharmaceutics II

• The design, stability, and manufacturing process of a drug product impact how the release of drug from the product will affect rate of dissolution at the absorption site.
• Various dosage forms influence therapeutic decisions during drug administration.

Generic Drug Approval

• Generic and brand-name drugs are not always identical.
• Once a new drug application (NDA) for a drug is approved by the FDA, a patent is granted to the drug company.
• After the patent expires, other companies can manufacture and market generic versions of the drug.
• Generic drug manufacturers must submit an Abbreviated New Drug Application (ANDA).
• Generic products must contain the same active pharmaceutical ingredient, dosage form, and administration route as the brand-name drug.
• ANDA approval requires the generic drug to be a therapeutic equivalent to the brand drug, meaning it is proven safe and effective and is pharmaceutically equivalent and bioequivalent.

Generic Drug Approval II

• Generic drugs may contain different inactive ingredients (excipients) from the brand-name drug, such as coloring and preservatives.
• Bioequivalence ensures the same rate and extent of active drug reaches the site of action. The sum of pharmaceutical equivalent and bioequivalence establishes a therapeutic equivalent.

Routes of Administration and Associated Drug Dosage Forms

• Oral administration is the most frequent route for drug administration.
• Tablets are compressed solid dosage forms, while capsules enclose the drug in a hard or soft gelatin shell.
• Oral solutions include suspensions (insoluble particles in a liquid vehicle) and solutions (soluble particles in a liquid vehicle).
• An example of a solution is elixir (a hydroalcoholic vehicle) and syrup (a sucrose vehicle).
• Rectal administration is useful in patients who are vomiting or unconscious or unable to swallow.
• Suppositories are solid dosage forms that dissolve to release the drug.
• Parental routes, such as subcutaneous, intramuscular, intravenous, and intradermal, are used for injection.

Oral Route/Oral Dosage Forms

• Oral dosages are frequent administration choices, but slow response and inconsistent absorption can be disadvantages.

Modified Release Drug Products

• Most oral drugs are immediate release (IR)
• Modified-release forms alter time and/or rate of drug release, improving patient administration or having a desired therapeutic effect.
• This allows for once daily dosing or controlled GI tract absorption to help avoid adverse effects.
• Extended-release forms allow for a significant reduction in dosing frequency. Other terms include controlled-release, sustained-release and long-acting.
• Delayed-release formulations release portions of the drug at different times.
• Enteric-coated tablets dissolve in the intestines.
• Repeat Action tablets contain two layers with immediate and delayed release dosage.
• Targeted-release releases the drug at the desired physiological site of action
• Orally disintegrating tablets (ODTs) dissolve rapidly in the mouth and can be administered without water.

Modified Release Drugs II

• Advantages of modified-release drugs include sustained therapeutic blood levels, better patient adherence, and improved tolerability.
• Disadvantages include dose dumping, limited flexibility in dosage adjustments, and potentially larger product sizes.

Clinical Considerations for Oral Modified Release Dosage Forms

• Do not switch to immediate-release drugs from modified-release drugs without considering blood concentrations.
• Counsel patients not to crush or chew modified-release tablets or capsules, because this can alter the drug release rate and efficacy.
• Some modified-release tablets contain non-erodible plastic matrix shells or osmotic release and will be seen in stool.
• Empty shells, or "ghosts", of osmotic release tablets might also appear in stool.
• Consult drug resources as needed.

Modified Release via Transdermal Drug Delivery Systems

• Transdermal delivery allows drug to pass from the skin to the systemic circulation.
• Advantages include avoiding first-pass metabolism and providing extended therapy.
• Disadvantages include potential for contact dermatitis, lag time to drug effects, drug persistence after patch removal, and limitations to potent drugs delivering via this method
• Transdermal patches allow for controlled release and sustained drug absorption over long periods.

Clinical Considerations When Prescribing Drug Patches

• Consider drug absorption variability from application sites and the need for sterile and dry skin
• Ensure patients are removing old patches before applying new ones. Discard the removed patch.
• Avoid lotions, creams, or other substances that may affect drug permeation or absorption at the application site

Practice with Drug Database

• Use of Lexi-Comp database for information.
• Search examples include amoxicillin (an antibiotic), promethazine (an anti-emetic), and assessing if pantoprazole tablets should be cut.