Non-Sterile Compounding

1. Non-Sterile Compounding Adapted from Sterile & Non-Sterile Compounding found on SP site Jessica Tagerman, PharmD, RPh

2. Compounding is like cooking!

3. “What are we making?”

4. Medication- “What are we making?” i.e. “medication preparations”

5. “What are we making?”Dosage Forms • 3 basic categories of dosage formulations: • Topical • Applied to the outside of the body (skin, nails, hair, eyes, etc.) • Some formulations made via non-sterile compounding, others made via sterile compounding • Enteral • Introduced into the GI tract in some way (orally, rectally, sublingually, etc.) • Parenteral • Literally means “around the GI tract”, but we use it to describe anything injectable. These are made via STERILE compounding. Why do so many dosage formulations exist?

6. “What are we making?”Solid Dosage Forms • Usually given by enteral route • Advantages • Easy to package, transport, store, and dispense • Convenient for self-dosing • Lack smell or taste (except has anyone ever smelled Metformin? Or an antibiotic?) • Very stable • Pre-divided dosage form- no need to measure • Can formulate as sustained or delayed release

7. “What are we making?”Solid Dosage Forms • Tablets • Capsules • Effervescent salts • Implants/Pellets • Lozenges, troches or pastilles • Powders • Suppositories

8. “What are we making?”Solid Dosage Forms: Tablets • Easy to administer • May be scored (easy to cut in half) • Prepared by compression or molds • Many different types • Enteric-coated: dissolves and absorbs in the intestines • Sugar-coated: masks bitter tastes • Film-coated: Helps with sustained release formulations • Sublingual: dissolves beneath the tongue • Buccal: dissolves and absorbs between the cheek and gum • Multiple-compressed: has multiple layers • Chewable • Extended release

9. “What are we making?”Solid Dosage Forms: Tablets, Types of Extended Release Products Do NOT crush or chew any type of extended release product (Why?) • Controlled diffusion (CD) • Controlled release (CR) • Controlled release tablet (CRT) • Long acting (LA) • Sustained action (SA) • Sustained release (SR) • Time delay (TD) • Time release (TR) • Extra long (XL) • Extended release (XR) • Immediate release (IR)

10. “What are we making?”Liquid Dosage Forms • Solution: contains a solute that is completely dissolved in a solvent • Aromatic waters: water-containing oils that have a smell and are volatile • Elixir: Clear, sweetened flavored hydroalcoholic solution with water and alcohol that may or may not be medicated • Enema: administered rectally for cleansing or drug administration • Extract: Process by which active ingredients are removed from their source by application of solvents • Douche: irrigating or bathing solution • Isotonic: A liquid that has the same osmolarity of another substance (example: normal saline is isotonic with blood) • Spirits: Alcoholic solutions with volatile aromatic ingredients. Most commonly used as flavoring agents. • Syrups: Aqueous solutions with sucrose or sucrose substitutes • Tinctures: Alcoholic solutions of pure chemicals or extracts

11. “What are we making?”Liquid Dosage Forms Continued • Dispersion: Solute dispersed through a dispersing vehicle; not completely dissolved. Many times has the same meaning as suspension. • Suspension: solid particles dispersed in a liquid vehicle; may be oral, topical, or injectable. ALWAYS use which auxiliary label? • Emulsion: Mixture of oil and water (o/w) or water in oil (w/o); oral emulsions are ALWAYS oil in water. A type of suspension.

12. “What are we making?”Liquid Dosage Forms • Advantages • Effective more quickly than solids • Easier to swallow (oral versions) • Convenience • Flexibility in dosing • Disadvantages • Deteriorate more quickly • May require special sweetening or flavoring • Require preservatives • Possible inaccurate dosing • Bulkier to carry

13. Ophthalmic Agents • Not commonly compounded • Must consider the following factors: • Sterility – must be sterile, achieve via autoclave, filtration, gas or radiation • Clarity – free from foreign particles, use filtration • Stability – Affected by chemical nature of the drug • Buffer and pH – 7.4 • Tonicity – isotonic has tonicity = to 0.9% NaCl • Viscosity – (resistance to flow)-agents used to prolong the contact time in the eye and enhance absorption

14. “What are we making?”Topical Dosage Forms • Collodion: Contains pyroxylin and is dissolved in alcohol and ether • Liniment: an emulsion or alcoholic or oleaginous solution applied through rubbing • Lotion: topical liquid that contains insoluble solids or liquids • Gel: two phase system with an extremely fine particle that when mixed is difficult to distinguish from the other substance; considered a semisolid form • Ointment: viscous semisolid preparation, usually thick and greasy • Anhydrous: absorb water; but are insoluble in water and not washable in water • Oleaginous: insoluble in water, do not contain or absorb water, not washable with water • Paste: more solid than an ointment • Cream: An emulsion of oil and water in equal proportions; thicker than lotion and maintains it’s shape • Transdermal Patches: Applied to the skin and absorb slowly through the skin into the blood stream

15. “What are we making?”Inhalants • Aerosols: spray in a pressurized container; contains a propellant that will carry the active ingredients • Spray: Container with a valve assembly that will emit a dispersion of gas, liquid, or a solid • Nebulizer: a machine used to administer medication in the form of a mist into the lungs

16. What “learning manual” is teaching us to cook?

17. What “learning manual” are we using to help us compound? The non-sterile compounding “guide” is USP-795

18. What equipment am I using to cook?

19. What equipment am I using for non-sterile compounding? Filter Paper Mortar and Pestle Graduated Cylinder Pipette Spatula Pharmaceutical Weights

20. What equipment am I using for non-sterile compounding? • Beakers: Glass or plastic, used to estimate and mix solutions • Class A Balance: Required in all pharmacies, used to weigh small quantities, has a sensitivity requirement of 6 mg. Lowest weighable quantity (LWQ) is 120 mg and maximum weighable quantity is 120 grams. • Counter balance: For bulk substances, used to measure up to 5 kg with a sensitivity of 100 mg • Digital Balances: Used most commonly, sensitive to a 10th of a mg. Used to replace Class A Balances. • Compounding (ointment) slab: Usually glass or ceramic, used to mix compounds

21. What equipment am I using for non-sterile compounding? • Filter paper: Used to filter a SOLUTION (not suspension, why?) • Forceps: Used to pick up pharmaceutical weights (can’t use hands, why?) • Funnels: Used to filter or pour liquids • Glycine paper: Placed under substances to be weighed • Graduated Cylinders: Used to measure liquids, most accurate method. • Master Formula Sheet: Pharmacy compounding log. Lists ingredients, quantities, and preparation steps for all compounds (Basically, a recipe that can be enlarged or reduced to fit specific prescriptions) • Mortar and Pestle: Used to mix ingredients

22. What equipment am I using for non-sterile compounding? • Glass: used to mix liquids and semisolids • Wedgwood: used to triturate crystals, granules, and powders • Porcelain: similar to wedgewood, usually used to blend powders • Pharmaceutical weights: Brass weights available in both apothecary and metric systems of measure . Should never be touched by hand. Should be calibrated at least once a year. • Pipettes: Used to measure volumes less than 1.5 mL • Sink with hot and cold running water: Required by law in all dispensing pharmacies • Spatula: May be rubber, plastic, or steel. Rubber preferred because it can withstand corrosive substances.

23. Capsule Sizes • The higher the number, the smaller the size • The largest capsule is 000

24. What techniques are we using to cook?

25. What techniques are we using to compound? • Blending: Act of combining two substances • Comminution: Act of reducing a substance to small, fine particles • Geometric Dilution: technique used to mix two ingredients of unequal amounts • Levigation: Trituration of a powder with a solvent that the drug is insoluble in (usually glycerin) • Pulverization by intervention: Reducing the size of a particle in a solid with the aid of an additional material • Sifting: Used to blend or combine powders • Spatulation: Mixing powders or ointments using a spatula • Trituration: Rubbing, grinding, or pulverizing a powder to create fine particles • Tumbling: combining ingredients in a bag and shaking it

26. What techniques are we using to compound?Measuring Liquids • Make sure that the amount of liquid being measured is not less than 20% of the volume held by the graduated cylinder • Pour liquid down the center • Keep on stable surface and watch at eye level • Observe measurement at the BOTTOM of the meniscus

27. What techniques are we using to make capsules?The Punch Method • Triturate ingredients into fine powder • Mix using geometric dilution • Use enough ingredients for several extra capsules • Place powder on ointment slab so that the depth is half the size of the desired capsule • Hold capsule vertically (and open) and punch into powder • Place the cap on a capsule and measure it against an empty capsule to determine counterweight

28. Cooking: What concerns may arise about the final product? Poor tasting food Burnt food Undercooked food

29. Non-Sterile Compounding: What concerns may arise regarding the final product?

30. Product Stability • Affected by many factors • Dosage form • Humidity • Ingredients • Light • Material of the container • Order and method of preparation • Temperature • Use Trissel’s handbook on injectable drugs for information about stability of IV compounds

31. Signs of Incompatibility • Physical • Precipitate • Change in pH, use of buffers, or type of solvent • Example: calcium and phosphate form a precipitate • Visually inspect medications for incompatibilities • Chemical • Chemical reaction between 1 or more ingredients • May not be visually noticeable • Sometimes caused by presence of light • Therapeutic • Mixing 2 or more drugs results in change in therapeutic response • Interaction

32. Beyond Use Dating • 6 month rule or 1 year rule used • 6 month rule: use ¼ of the product manufacturers expiration date OR 6 months, whichever occurs first • 1 year rule: maximum of 1 year BUD assigned as long as it doesn’t exceed the expiration of the manufacturer • Other BUD methods used in compounding, but don’t worry about it for the exam (based on presence of water and preservatives)

33. https://www.youtube.com/watch?v=4Bw7ug5X7zg Questions?