Compounding Flashcards
USP Compounding chapters
USP 795: non-sterile compounding
USP 800: hazardous compounding
USP 797: Sterile compounding
Non-sterile compounding definition
Primarily used to prepare a dose or formulation that is not commercially available, avoid an excipient, or add flavor.
Administered only by mouth, tube, rectally, vaginally, topically, nasally, or ear.
USP 795 divides into complexity: Simple; requires following simple directions. Moderate; specialized calculations, or making something without stability data. Complex; specialized dosage forms such as transdermal.
Compounding space should be specific to non-sterile in a separate space from the dispensing part. There must be potable water and purified water.
Sterile compounding definition
Used to prepare injections (IV, IM, SQ), eye drops, irrigation, and inhalations.
Small volume is </=100mL, and large is >100mL.
Primary engineering control (PEC) should be ISO 5. Negative pressure must be used for chemo, and is generally class II or III biological safety cabinet.
Secondary engineering control is the buffer room and has an ISO of 7.
Segregated compounding area has ISO 5 hood in non-sterile area.
USP requirements for air in sterile compounding
In critical areas, ISO must be 5 or less. The buffer must be ISO 7, and the anteroom for garbing must be ISO 8 for positive pressure (non-HD), and ISO 7 for negative pressure (HD).
Room air is generally ISO 9.
HEPA, high-efficiency particulate air filters are 99.97% effective at removing 0.3 micron particles. Vertical hoods have the HEPA at the top, and in a laminar or horizontal hood it is in the back. Compounding is done in the first air in the direct compounding are of the hood. Must be certified every 6 months or after movement.
Use 70% IPA to decontaminate, leave 6 inches from the hood.
Positive pressure pushes air out of the area, and is used for non-hazardous compounding. Negative pushes air into the area, and is used for hazardous compounding.
Air changes per hour: non-sterile hazardous drugs must have 12 ACPH, sterile C-SEC must have 30, and in a C-SCA must have 12.
USP requirements for physical spaces in sterile compounding
Surfaces must be smooth, impervious, and free from cracks and crevices.
Cleanroom suites have one or more PEC inside a buffer room and is entered through an anteroom.
Primary engineering control is a device that provides ISO 5. A laminar airflow workbench can be used for non-hazardous and has an open front and air moves outwards. A compounding aseptic isolator has a closed front in a buffer room or segregated area.
Secondary engineering control is also called the buffer room and has ISO 7. The anteroom connects the buffer to the pharmacy and is ISO 8 used for garbing. The line of demarcation separates it into clean and dirty.
USP beyond use dates
Emergency use compounding has a BUD of 1 hour. The segregated area without a buffer or anteroom is used for low risk CSP and has max BUD of 12 hours.
Hazardous drugs from NIOSH
Antineoplastic drugs/chemotherapy
Non-antineoplastics:
Mifepristone, misoprostol, chloramphenicol, warfarin, fluconazole, voriconazole, abacavir, entecavir, zidovudine, cidofovir, ganciclovir, valganciclovir, isotretinoin, dronedarone, acitretin, azathioprine, leflunomide, fingolimod, terifluonomide, dutasteride, finasteride, pamidronate, zoledronic acid, dexrazoxane, paroxetine, exenatide, liraglutide, lomitapide, clobazam, clonazepam, carbamazepine, oxcarbamazepine, eslicarbazepine, divalproex, fosphenytoin, phenytoin, topiramate, vigabatrin, zonisamide, colchicine, ivabradine, spironolactone, ribavirin, androgens, estrogens, oxytocin, dinoprostone, progesterones, SERD/SERM, ullipristal, methimazole, propylthiouracil, temazepam, triazolam, defepirone, dihydroergotamine, apomorphine, rasagiline, ambrisentan, bosentan, macitentan, riociguat, ziprasidone, cyclosporine, mycophenolate, tacrolimus, sirolimus.
Compounding staff requirements
Standards include hand hygiene, garbing and gloving, cleaning and disinfectants, and sterile preparation.
Gloved fingertip test: Initially, then annually or semi-annually for high-risk CSP. A gloved sample is collected on a TSA tryptic soy agar plate. Passing requires 3 consecutive samples with zero colonies, and ongoing must have <3 colonies.
Media fill test: Determines aseptic technique. Turbidity or cloudiness determines contamination. Passing happens after 14 days of no turbidity.
Refrigeration requirements
SEC should be checked once daily and maintain <68F/20C.
The regular fridge should be checked once daily and maintained at 2-8C/36-46F.
A vaccine fridge should be checked twice daily and maintained at 2-8C/36-46F.
A regular freezer should be checked once daily and maintained at -25–10C.
A vaccine freezer should be checked twice daily and maintained at -50–15C/-58–5F.
Air and surface testing requirements
Air sampling for contaminants every 6 months.
Frequently touched surfaces tested at the end of every workday.
Air pressure testing once daily, or every work shift.
Humidity testing once daily to maintain <60%.
Cleaning requirements
PECs should be running continuously. If they stop, then they must be cleaned with a germicidal agent and then with IPA (70% isopropyl alcohol), and must remain on for 30 minutes prior to compounding.
Daily cleaning should be done on the PEC first at the end of the day with a germicidal agent and IPA. Cleaning is top to bottom, back to front.
Example order: Clean ceiling from back to front, then grill over HEPA top to bottom, the side was back to front, IV bar and hooks, clean equipment, and lastly the bottom surface back to front.
Hazardous cleaning
Sanitation is done in a specific order:
Deactivation and decontamination: 2% Na hypochlorite or bleach, or peroxide to reduce HD toxicity. Can neutralize afterward using Na thiosulfate, alcohol or water.
Cleaning: germicidal agent; Quat5, Ammonium, Phenolics to remove dirt and microbes.
Disinfection: 70% IPA to destroy and inhibit microbes.
Perform wipe sampling every 6 months.
Disposals of hazardous material
Yellow: trace bin; outer chemo gloves, gown, and shoe coverings.
Black: bulk; remaining drug, IV bags, any visible amount of drug.
Red: Non HD infectious material; used syringes.
Garbing for sterile compounding
Remove watches, rings, bracelets, makeup, and artificial nails.
Don headgear and masks, shoe covers over the line. Two shoe covers for HD.
Hand hygiene.
Don a gown, then enter buffer area, then disinfect hands with alcohol, chlorhexidine, or povidine iodine (Betadine).
Don gloves (two ASTM D6978 chemo-rated gloves for HD) and sanitize with IPA.
Instruments to measure volume
Cylindrical and conical graduates: has to be over 20% of the volume needing to be measured (5mL for 100mL graduated cylinder).
Syringes: good for small volumes and viscous fluids. In general, do not recap, use with safety features, and if it must be recapped use the scoop method. Do not confuse oral with parenteral, and use the closest size available.
Pipettes and droppers: volumetric has a specific volume help, Mohr pipette is graduated. Droppers measure 45-55mg water when held vertically.
Instruments to measure weight
Balances: class A or III have internal weights for 1 gram, and external weights for >1 gram. Torsion balances have a sensitivity of 6mg (6mg will move the dial one division). Minimal weighable quantity is based on the sensitivity and error rate of 5%: SR/error, or 6mg/5%=120mg. Electronic balances do not need to be calculated but must be tared.
Instruments to mix things
Mortars and pestles: may come in glass, Wedgwood, or porcelain. Glass is for liquids, Wedgwood is for crystals and large powders, and porcelain is for fine powders and gummies.
Spatulas: Do not use the steel one if the mix has metal ions. Rubber is for corrosive material.
Ointment slabs: pretty much a work table area.
Powder sieves: sifters for uniform particle size.
Electronic instruments to mix things
Ointment mills: grinds and homogenizes preparations, and can reduce particle sizes.
Homogenizers: or electric mortar and pestle is used for semi-solid preparation, ointments, and creams.
Grinders: similar to coffee bean grinders.
Magnetic stirrer: for dissolving then mixing.
Heating devices
Hot plates: require water baths to keep temperature uniform.
Microwaves: may be uneven temperatures, and heat quickly.
Instruments to create pills
Tablets: tablet presses take a damp powder to mold and press together, then allowed to dry.
Capsules: soft gels or hard gels are used. Made of gelatin from either pork or hypromellose (plant based). Sizes are backward, with 000 being the largest, and 5 being the smallest.
Tube sealers: uses heat to shut tubes by crimping together.
Surfactants
Lowers the surface tension and keeps oil and water from separating quickly. Forms an amphiphilic micelle structure. Some form electrically charged surfaces, or a film.
Wetting agents: Helps with liquids and solids. Levigating agents are a form of wetting agent.
Emulsifiers: immiscible liquids.
Suspending agents: solid dispersed in a liquid. Ex. Ora-Sweet and Ora-Plus (slightly acidic).
Levigating agent: levigation and tituration are used to grind particles. Tituration is the dry method. The levigating agent includes glycerin (water-based) or mineral oil (oil-based).
Foaming agents: detergents generally. Anti-foaming is used in sterile compounding and includes simethicone.
Delivery vehicles: PEG and poloxamer, or PLO.
Oil in water is generally oral, and water in oil is generally topical.
HLB is 0-20 to determine lipid and water solubility. 0 is lipid, and 20 is water.
Examples: glyceryl monostearate, PEG 400, span 65, sorbitan tristearate, tween 81, polyoxyethylene sorbitan.
Oxidation-Reduction degradation
Oxidation: loses electrons
Generally, hydroxyl groups (-OH) are directly bound to an aromatic ring. Examples: catecholamines, phenolics, and aldehydes.
Catalyzed by heat, light, and metal ions.
Prevention includes light protection in amber vials, temperature controls, chelators (commonly with ED in the name such as EDetate sodium or Edetate calcium disodium), antioxidants (vitamin C, E, ascorbyl palmitate, ascorbate, bisulfate, sulfoxylate, thiosulfate), and controlling pH.
Reduction: gains electrons, occurs with oxidation
Hydrolysis degradation
Cleavage of a bond through water.
Generally, esters, amides, and lactams with carbonyl groups (C double bonded to O) undergo hydrolysis. Aspirin to acetic acid and salicylic acid.
Prevention is from protection against moisture through desiccants, lyophilized/freeze-dried, hygroscopic salts, and prodrug formulations.
Photolysis degradation
Breakage of covalent bonds through UV light.
Sensitive groups include ascorbic acid, folic acid, nitroprusside, and phytonadione injection.
Prevention is primarily through light protection.
