Compounding III: Documentation & Preparation (RxPrep 2022)

• COMPOUNDING & HAZARDOUS DRUGS W -=T / ' ' , ,. ... - ~.. . . - . .. CHAPTER 17 COMPOUNDING Ill: DOCUMENTATION & PREPARATION NON-STERILE PREPARATIONS DOCUMENTATION Two very important records that each compounded product must have are the master formula record and the compounding record. T...

• COMPOUNDING & HAZARDOUS DRUGS W -=T / ' ' , ,. ... - ~.. . . - . .. CHAPTER 17 COMPOUNDING Ill: DOCUMENTATION & PREPARATION NON-STERILE PREPARATIONS DOCUMENTATION Two very important records that each compounded product must have are the master formula record and the compounding record. The master formula re.cord is the recipe that is followed to compound a preparation. The compounding log (or record) is the log book of all products made at the pharmacy (see images on the following pages). The documentation in the compounding log must be detailed enough that another trained person can replicate the steps involved in the preparation, evaluate if the procedure was correct and trace the origin of all components. The pharmacy must keep records of steps and processes that relate to the compounded product, such as equipment cleaning, calibration and maintenance, temperature logs for the refrigerator, freezer and room (ambient) air, and records of chemicals, bulk drugs and drug products. PREPARATION STEPS Prior to preparing to compound, the pharmacist will need to evaluate the prescription and determine if it is appropriate for the patient, and whether the proposed formulation is reasonable (e.g., is the formulation likely to have acceptable stability and palatability?). When ready to compound, the initial steps will be similar for most formulations, such as calibrating equipment and weighing ingredients. The final steps will be similar, and include packaging and performing quality control (QC). What changes most are the steps in between, which depend on the type of formulation to be prepared. Always review the Safety Data Sheets (SOS) for each bulk ingredient to determine safety procedures for the staff who will compound the preparation, including the recommended personal protective equipment (PPE). 271 17 I COM PO UNDIN G Ill : DOCUMENTAT IO N & PREPA RATION MASTER FORMULA #3755 IBUPROFEN 200 mg SUPPOSITORIES Formula: Ibuprofen 200mg Suppositories Strength: Quantity: 200mg In redients: Quanti Ibuprofen 0 .2 gm SilicaGel 0.02 gm Base MBK (Fatty Acid Base) Calculate Procedure: Note: calculations should be made to make an excess amount of 10% of the amount needed. l . Calculate and weigh ingredients to prepare 10 Ibuprofen 200mg suppositories in the blue mold which is calibrated to 1.28 gm of Base MBK per suppository. Use the Suppository, General Formula worksheet. 2. Melt Base MBK at 50 degrees C using a hot water bath. 3. Using a mortar and pestle, triturate ibuprofen and Si/icaGe/ together to a fine powder. 4 . Sift the powder from Step 3 into the melted Base MBK while stirring . The use of a strainer helps to ensure small particle size. 5 . Turn off heat and stir until mixture looks consistently suspended . 6. Pour into molds (may use a large bore syringe if available) and allow to cool to room temperature. 7. Package in universal sleeve and label. MASTER FORMULA Recommended Expiration: 180 days Recommended Storage/ Refrigerate Auxiliary Labels: Notes: Compound's Official or Assigned Name Strength, Dosage Form Calculations Ingredients, with quantities Stability & Compatibility data, with references Equipment Preparation/Mixing instructions Labeling information Packaging/Storage requirements Quality Control (QC) procedures, with expected results BUD, recommended Description of final product 272 Rx PREP 2022 CO U RS E BOOK I Rx PREP ©2021 , © 2022 IFormula# 3755 J Raindrop Compounding Pharmacy COMPOUNDING RECORD PRODUCT Drug Name and Strength Use/Dosage Form Q.iantity Ibu r ofen 200 m Su #10 ositories Control/Rx# 37-865 Date 6-7-21 INGREDIENTS Ingredient NDC or Manufacturer# QTY LOT EXP Ibuprofen powder USP Silica qel MBK base Disposable supp molds 18100-25, Spectrum 51935, Spectrum 30-156, PCCA Apothecary 2q 0.2 q 12.8 g A3472-19 51008-19 1234-18 3/24 12/23 2/23 COMPOUNDING DIRECTIONS & PROCEDURES 2. Wei 9. Trimm laced in refri erator to harden for 1 hour form sur face, even color ositor i COMPOUNDING RECORD OR LOG Weighed by: Dae L -- ' - - - - ---1 Compound's Official Name or Assigned Name Reference # for the Master Formula Prepared by: -Dae L - ~ - - - ------11 Strength, Dosage Form Specific to t his preparation Ingredients (including manufacturers/sources, lot numbers & expiration dates) Steps followed QC results BUD, actual (assigned) Description of final product The product's assigned lot or prescription numbera duplicate prescription label can be attached to the log Staff involved with the preparation (1) Compounder, (2) Person who did QC, (3) RPh who approved final product, with dates u £ I !Q) _ _ _ _ _ (QI What you DID 273 17 I COM POUNDIN G Ill : D OC UMENTAT IO N & PREPA RAT IO N Preparation of Non-Sterile HDs Compounding Steps Non-sterile hazardous drugs (HDs) should preferably be compounded in a containment primary engineering control (C-PEC), discussed in the Compounding I chapter. This option is not always available, and efforts must be made to protect the staff with techniques to reduce exposure (e.g., splitting tablets while enclosed in a sealed plastic bag). All equipment used for HDs, including counting trays and spatulas, must be dedicated for HDs only, and sanitized after use. Make the product according to the maste1• formula. The final formulations, when possible, should be placed into unitdose sealed packaging, and placed into a plastic bag with a hazardous label (see the image on the right). The Formulation Determines the Type of Garb rm '1:)Teva Canada Limited Initial Steps 1. Calculate the quantities needed for each component. 2. Gather aii the components and the equipment needed. 3. Wash equipment, if needed, and calibrate. 4. Perform hand hygiene and garb. The calculations required for compounding will often require unit conversions, percentage and ratio strengths, basic algebra and changing concentrations with Q1C1 = Q2C2 and alligation. 22% 274 Completion Steps 1. Package the product and apply the container label and any 2. Perform QC: validate the weight, check the product for PPE is reviewed in the Compounding I chapter. Percentage Strength: 20 g = Xg X = 22.222 g or 90g 100 g Other steps are unique to the formulation type, such as calculating the density factor to make suppositories. needed auxiliary labels. A duplicate container label can be placed on the compounding record. Minimally, PPE (i.e., garb) should include a clean lab coat and gloves when preparing non-sterile, non-hazardous preparations. The SDS will provide information if other PPE is needed. For example, the SDS for benzalkonium chloride recommends using gloves, a gown and eye/face protection. Benzalkonium chloride should not be exposed to skin or mucus membranes, and the SDS provides instructions to manage exposure, such as steps to take if the compound is inhaled. Example: What is the percentage strength (w/w) of ketamine in the compounded topical pain gel? (Round to the nearest WHOLE number.) Most formulations will require common techniques, such as trituration, levigation and geometric dilution. _. TOPICA.l PJ\IM GU - .......,._ Gl,~om ,--~~ 20, 10, 21, I''' 75g Pro&.toliaJOr~t, 200mg Poloumer F 127 JO'Jlo Q~ ~d 90g mixing adequacy, color, clarity, odor, consistency and pH. Enter the measurements and observations in the compounding record. 3. Counsel the patient, and if any subsequent ADRs are reported, add them to the compounding record. PREPARING POWDERS REDUCING PARTICLE SIZE When making a compound with dry ingredients, the goal is to make an evenly-distributed mixture with fine powder. Comminution means to reduce pa1,ticle size by grinding, crushing, milling, vibrating or other processes (manual or mechanical). The compounder likely starts off with coarse granules or broken tablet pieces. Powders will be finely ground into particles that range in size from 0.1 - 10 microns. After the powder has been ground, it is placed into a sieve. Using a powder sieve ensures uniform particle size rcr, Mo:;ideof/ 5/rnH ers!ock com Sieves, which are sifters, are used to ensure that the particle size is uniform. The powder is put into the sieve and sifted through the mesh. Once placed into the sieve, the powder is stirred with a sieve brush or a plastic spatula to force the particles through the mesh. A high mesh size has many wires that make many holes, and only a fine powder will get through the mesh. The sieve number is based on the number of holes per inch (e.g., #100 sieve has 100 openings/inch). Rx PREP 20 2 2 CO U RS E BO O K Three Main Methods of Comminution Trituration: a general term used to mean "mix thoroughly" (or make the product homogenous) . Pharmacists most commonly associate trituration with grinding tablets with a mortar and pestle until a fine powder is achieved, but the term can describe liqu ids (e.g., tritu t·ating an emulsion by shaking it). I Rx PR EP © 2021, © 2022 Comminution Levigation and spatulation: Levigation involves triturating the powder with a mortar and pestle and incorporating a small amount of liquid (called a levigating agent or wetting agent). This helps with the gl'inding process and creates a uniform paste. Grind into a fine powder Just like trituration, but with a levigating agent <{;JRxPrep o Spatulation is similar to levigation, but performed on an ointment slab with a spatula (not with a mortar and pestle). Pulverization by intervention is used for crystalline powders that will not crush easily. The Cl'ystals are dissolved with an intervening solvent and mixed until the solvent evaporates. When the powder recrystallizes, the particles are finer. MIXING INGREDIENTS Geometric dilution is a method of mixing ingredients to ensure that ingredients are evenly distributed in a diluent or delivery vehicle. A small amount of the drug is mixed into an equal amount of the diluent. After the initial small amount is thoroughly mixed, another equal amount of the ingredients is mixed in. This is repeated until all the ingredients are mixed together. Geometric dilution can be used with dry powder ingredients alone, or when making a paste. When using multiple ingredients, begin with the ingredient that has the smallest quantity, followed by the ingredient with the next smallest quantity, and up until each has been added. With each addition, the amount should be roughly doubled. Geometric Dilution is used to Prepare Homogenous Products Let me explain how to do geometric dilution. We use geometric dilution to mix all types of components together to make a smooth, evenly-distributed (homogenous) preparation. • • The drug powder (ground smooth!) is already on the ointment slab. A (roughly) equal amount of the ointment base is added. This will make about double the amount, then we repeat the process. Why didn't you dump it all in at once? w-;; - It will not be a homogenous~ (even) mixture. The ointment will feel gritty and the drug dose will be provided unevenly. ;e .:: Would you use the same ,' Both would be fine! Geometric dilution works well to mix two (or more) process if you were mixing in a mortar? What substances together. Bakers use a similar process, adding a little at a time, to make if you were mixing two an even, smooth batter for a yummy powders together? cake! Who wants to eat a lumpy cake? ,jjj,' 275 17 I CO MP O UNDING Ill : DOCUMENTATION & PREPARAT IO N DOSAGE FORMS SOLUTIONS, SUSPENSIONS AND EMULSIONS r I 1 A SOLUTION is a solute dissolve~ a solvent (such as NaCl, dissolved in water). Solutions are homogenous (consistent, uniform throughout), If the solute concentration is too high, it can lead to unwanted precipitation (see below). Solutions are usually for oral use. Lotions are topical solutions. TYPES OF SOLUTIONS: Syrups are oral solutions with sucrose, other sugars or artificial sugars. Elixirs are sweet hydroalcoholic solutions used for drugs that would be insoluble in a purely aqueous formulation. Hydroalcohol is a mixture of alcohol and water. Tinctures are plant or animal extracts dissolved in alcohol or hydroalcohol. Spirits are alcohols or hydroalcohols of volatile, aromatic compounds such as camphor. Volatile means the compound vaporizes (evaporates) easily. A SUSPENSION is a solid dispersed in a liquid. It is a two-phase heterogeneous mixture. A wetting agenVlevigatlng agent is a type of surfactant used to incorporate an insoluble drug into a liquid, which makes a suspension. A desirable suspension does not have rapid precipitation of the solids; particles can be redlspersed easily by shaking. An EMULSION is a liquid dispersed in a liquid. It is a two-phase heterogeneous mixture. Emulsions are oil-in-water (oil droplets in an aqueous vehicle) or water-in-oil.· An emulsifier is a type of surfactant that is used to reduce the surface tension between two liquids (e.g., oil and water). The emulsifier allows the two phases to come closer together. To make the emulsion, the emulsifier will need to be carefully chosen, according to the hydroph!llc·lfpophillc b~lance [1-tlB) number (see the Compounding II chapter). ·rhe phase that is present as droplets is the dispersed, internal phase or discontinuous phase, and the phase in which the droplets are suspended is the continuous or external phase. PRECIPITATION/SEDIMENTATION is when the dispersed phase settles (clumps) together. The process of a solid settling on the bottom of a container is sedimentation. This can happen with suspensions and ~ulsions, and less commonly with solutions. Shake or gently roll to re-disperse. El;ll GmµhicsRF.com!Shutterstock.corn How to Prepare Solutions Prepare the ingredients, and reduce the particle size of the drug/s to form a fine powder. The initial step in preparing any solution will be to determine if the solute will dissolve in the solution. The drug should remain soluble at different temperatures that may be encountered, including during refrigeration, if required for stability. If the drug is not soluble (e.g., will not dissolve in water), a suspension or a different solvent may be preferable. The dissolution rate can be used to determine the time it will take for the solute to dissolve. The dissolution rate is calculated using Fick'S First Law of Diffusion. A larger surface area (i.e., smaller particles), stirring the preparation and using heat will increase the dissolution rate. Determine if the solution will be stable at the desired temperature. A buffer system may be needed to resist changes In pH (see the end of this chapter). A preservative may be needed to protect against microbial growth, including bacteria, fungi and yeast. Flavorings, sweeteners and coloring agents can be added. Package the solution and apply appropriate auxiliary labels. How to Prepare Suspensions Prepare the ingredients, and reduce the particle size of the drug/s to form a fine powder. Wet the powder, and levigate to form a paste. Continue to add liquid in portions. Add a surfactant to help keep the suspension dispersed. Transfer the mixture into a conical graduate or the container in which it will be dispensed, and QS to the final volume. A homogenizer will help make a uniform suspension. A preservative may be needed to protect against microbial growth, including bacteria, fungi and yeast. Flavorings, sweeteners and coloring agents can be added. Package the suspension and apply a BUD. Even with surfactants used as suspending agents, suspensions are inherently unstable, and will need to be redispersed (i.e., shaken) prior to use. 276 RxPR EP 202 2 COURSE BOOK I Rx PRE P ©2021, ©20 22 ingredients by the melting temperature, and melt in that order, starting with the highest melting point. How to Prepare Emulsions ( 4partsoil j ( 2 parts water ) 1 part gum (e.g., acacia) Emulsions can be made by either the Continental or English gum method; mixing oil, water, and an emulsifier (gum) in a 4:2:1 ratio . Continental (dry gum) method: 1. Levigate the gum with oil. 2. Add the water all at once. 3. Triturate by shaking in a bottle or mixing in a mortar until a cracking sound is heard and mixture is creamy white. English (wet gum) method: 1. Triturate the gum with water to form a mucilage (thick and sticky like mucus). 2. Add oil slowly while shaking or mixing. 3. Add other ingredients as in the dry gum method. 4. Add other ingredients by dissolving them first in solution and adding a quantity of water sufficient to make (QS) up to the final volume. 5. Homogenize (with a homogenizer machine). Hint: It rains a lot in England (wet), and the oil is added slowly because you cannot drive too fast in the rain. The continent is dry, and you can add the water quickly (all at once). Eutectic Mixtures A eutectic mixture means that the combination of the ingredients (when mixed together} will melt at a lower temperature than either of the individual component's melting tempel'atures (see comic). The lower melting point of the eutectic mixture allows it to penetrate the skin more easily than the individual components. Eutectic mixtures can create difficulty during compounding: If a pharmacist is not aware that the components form a eutectic mixture, the temperature on the hot plate can be set too high and the mixture can burn. If the components are solid powders at room temperature, the mixture of the powders can melt and turn the mixture into a sticky mess, ruining the dry preparation. An adsorbent powder (magnesium oxide, magnesium carbonate or kaolin) can be used to keep the powder dry. The yellow one melted at 76°C, and the blue one melted at s2°c. POWDERS Powders are fine particles of a solid. A dose of medication can be given as the dry powder (put into liquid or a small amount of soft food) for someone who is not able to swallow capsules or tablets, such as a small child or an elderly person with dysphagia. Powders are used to prepare tablets, capsules, inhalations, suspensions, ointments, creams and other topical treatments. Powders often include excipients. The excipients listed here are specific to the powder part of the preparation, and are commonly used for the purpose stated: Glidant/lubricant to improve the flowability of a powder: magnesium stearate. Surfactant to neutralize the static charge and keep the powder from floating away: sodium lauryl sulfate. That's strange! When I mixed them together, the two compounds melted at ~ • c . It's lower than either one of t ~ e m ! r• • • The two ingredients formed a eutectic mixture, with a lower melting point than either of the components. How to Prepare Powders Reduce the size of the powder. This may require breaking down tablets with a grinder. followed by trituration or levigation. Sift the powder through a sieve (pictured previously) onto glassine paper. If the amount of powder per dose is very small. it will be necessary to add an inert filler (diluent). A filler could also be needed to provide a minimum weighable quantity if using a torsion balance (see the Compounding 11 chapter). A common diluent is lactose. Add the filler and other excipients using geometric dilution. Melting Point Order For any formulation, if melting ingredients, melt the ingredient with the highest melting point prior to adding the ingredient/s with lower melting points. Line up the Be careful! If two powders are mixed together, and they form a eutectic mixture, the powders could start to melt. A nice powder mixture can become a sticky mess! • ,. • 17 I CO MPOUN D IN G Ill: DOC UM ENTATION & PREP AR AT ION CAPSULES LOZENGES/TROCHES Capsules are soluble shells of gelatin (an animal product) or hypromellose (a vegetable product}, which are filled with the active drug, diluents (fillers} and Capsule-filling machine any other excipients. HardfQJ fe/iµe caprn ros/Shutterstock.co,n shell capsules are used most commonly in compounding, and are filled with powders. Soft-shell capsules are used mostly for oils. Glycerol and sorbitol are used as plasticizers to make the capsules less brittle and more flexible. Lozenges (or troches) can be hard or soft tablets that slowly dissolve in the mouth, or chewable tablets that are easily chewed and swallowed. Lozenges/troches are generally used to deliver a medication that acts locally in the mouth . A commercially available example is a clotrimazole troche for treatment of oral thrush. A lozenge contains the active drug in a base of sucrose or syrup for hard lozenges, PEG for soft lozenges and glycerin or gelatin for chewable lozenges. Flavoring agents and coloring agents may be added. The base is melted, mixed with the API and excipients, placed into a mold and allowed to cool back into a solid. How to Prepare Capsules Capsules are made by first triturating the dry ingredients and geometrically mixing with the fillers/other excipients. The powder is put into the capsules by either hand filling (also known as the "punch method") or by using a capsule-filling machine (see the Compounding II chapter for information on equipment). Hand filling: to begin, the powder is placed on powder paper or on an ointment slab. The pile of powder is smoothed with a spatula to a height about a third of the length of the capsule. The open end of the capsule is repeatedly "punched" into the pile of powder until the capsule is filled. When the base is filled, it is fitted with the cap. Manual capsule-tilling machine: these are small devices that help the pharmacist quickly load 50, 100 or 300 capsules. Plates help sort the capsule bodies and hold them upright and in place. The powder is put above the capsules on to a plastic sheet where a plastic spreader is used to move the powder into the capsules. A comb or tamper and a spreader are used repeatedly until the powder is packed into the capsules. Then, the caps are put over the capsule bodies. Common capsule sizes range from largest (size 000, -1 inch long} to smallest (size 5, -0.4 inches long}. Capsule bodies can be filled by hand (for a small number} or with a capsule-filling machine (for larger amounts). In addition to using a capsule-filling machine to add a powder formulation, liquids can be added to upright capsule bodies with a pipette or dropper. TABLETS There are many types of tablets, including molded tablets, sublingual tablets, buccal tablets, orally disintegrating tablets, chewable tablets, effervescent tablets and compressed tablets. The molded tablet is the most common tablet type made in compounding, and the compressed tablet is the most common type made in manufac turing. How to Prepare Molded Tablets The first step to compound a molded tablet is to triturate the dry ingredients and mix by geometric dilution. Alcohol and/or water is added to moisten the powder. The powder mixture should have a pasty consistency, which can be molded into tablets (using tablet molds), and allowed to dry. Coloring and a coating may be added. 278 CREAMS Creams, lotions, ointments, pastes and gels are delivery vehicles, and are described in more detail in the Compounding II chapter. Creams are semi-solid formulations intended for topical use. They contain more than 20% water and up to 50% oil. They spread easily and are reasonably hydrating. Creams are packaged in tubes and tubs. LOTIONS Lotions contain the most water (compared to other topicals), are more fluid than creams, and can be poured. They are easy to spread on the skin and they absorb quickly. Since lotions contain a lot of water, they can be delivered in pumps. OINTMENTS Ointments contain the least water; 0 - 20%, with the remainder composed of oil-based product/s. Ointments are a good delivery vehicle to provide a barrier to exposure (e.g., organisms, sun) and they prevent moisture loss which helps burn and scar healing. They are packaged in tubes or tubs. How to Prepare Ointments Powders should be triturated well, using a levigatlng agent. The levigating agent must be miscible with the base, which means they can mix together well (mixing "like with like" is a common compounding principle). The powder will be mixed into the ointment base, using geometric dilution. Certain ointments will require heat in order to mix the components together well. This is called the fusion method. Always use the lowest temperature possible. First, melt the ingredients with the highest mel ting point, then add the others, according to their decreasing melting points. Otherwise, undesired chemical reactions could occur. A water bath used to heat the ointment components will help prevent over-heating. Rx PREP 2022 COURS E BOOK I RxPRE P ©202 1 , PASTES How to Prepare Suppositories The ingredients in pastes are similar to ointments, but they are made thicker by adding more solid ingredients. They provide a protective barrier because they do not melt significantly at body temperature. There are three methods to prepare a suppository: Hand molding can be used when only a few suppositories are to be prepared, using a cocoa butter base. The cocoa butter is not melted. It is grated and then mixed with the drug/ s in a mortar and pestle or on a pill tile with a spatula. The mass is rolled into a cylinder, which is cut into suppository-size pieces. A tip is formed on one end to make insertion easier. GELS In the commonly-used fusion molding method, the base is gently heated, the ingredients are added, the mixture is poured into room temperature molds, and left to harden. If the base is poured into a cold mold, it can cause the suppository to crack and split. If the suppository does not harden, the molds can be refrigerated . Disposable plastic molds can be used for molding. Often, the suppositories are dispensed in the mold; suppositories are soft, and easily damaged. They are stored in the mold until needed. Gels are semisolids interpenetrated by a liquid. Gels serve as a versatile drug delivery system for various routes of administration; they can be used orally, topically (for local or transdermal drug delivery), vaginally and rectally. Gelling agents are added to increase the viscosity and thicken the product. Alcohol is added to some gels to decrease the viscosity. Pluronic lecithin organogel ("PLO gel") can be used for transdermal drug administration. Pre-mixed PLO gels are available. See the Compounding II chapter for details. In the compression molding method, the pharmacist will need to know the weight of each mold, and the drug's density factor (see above). The amount of base required to fill each mold is calculated, the base is grated, mixed with the drug and put into a cold compression mold. Lubricants can be applied to the mold so the suppositories can be removed more easily. If a lubricant is used it must be opposite of the suppository base in terms of solubility. The goal is to reduce friction. For example: glycerin or pmpylene glycol (both watersoluble) are good lubricants for suppositories made with oil-soluble suppository bases, while mineral oil or vegetable oil spray (oil· soluble) are good lubricants for water-soluble bases. SUPPOSITORIES A suppository base is either oil-soluble (oleaginous) or water-soluble. Oil-soluble bases include cocoa butter (known as theobroma oil) and hydrogenated vegetable oils (palm, palm kernel and coconut oils). Water-soluble bases include polyethylene glycol (PEG) polymers and glycerinated gelatin. If a drug powder is added to a base, the powder should be triturated to a fine consistency. If the preparation softens or melts easily, such as with theobroma oil (cocoa butter), the molds will need to be stored in the refrigerator. The melting point of theobroma oil is slightly below human body temperature. When theobroma oil is used as a suppository base, the suppository will start to melt when held in the hand. It is not possible to insert a melting suppository. Storing it in the refrigerator will make the suppository hard, and easier to insert. Storing it in the mold in which it was formed would be preferable. The drug will displace part of the base. If the drug has the same density as the base, it will displace an equal amount of volume. If the density is greater, it will displace less, and if it is lower, it will displace more. To calculate the amount of base displaced, the density factor of the drug is needed. The density factor can be found in compounding references, or calculated with the Paddock Method: l~:~:; " A-:+B © 20 22 Vaginal suppositories are used to treat conditions inside the vagina, such as a Candida infection, or conditions related to the female reproductive system, such as hormone replacement in a patient with menopausal symptoms. Rectal suppositories are used either to treat a local condition, such as hemorrhoids or distal ulcerative colitis, or to treat a systemic condition, such as pain and fever in a patient who cannot take oral medication (e.g., acetaminophen suppository). Suppositories bypass the oral route and largely avoid first-pass metabolism. Suppository bases must be hard enough to be briefly handled, but soft enough to melt easily once inserted. Storing the suppository in the refrigerator can make insertion easier. L __J COMPOUNDING KITS There are some companies that package pre-measured ingredients for a compounded product into "compounding kits." If the pharmacy does not routinely receive prescriptions for a certain product, it can be cost-effective (and easier) to purchase compounding kits as needed instead of purchasing the bulk ingredients. A = weight of the suppository blank, B = weight of medication per suppository, C = weight of medicated suppository. 279 17 I COMPOUNDIN G Ill: DO C UMEN TATION & PREPAR AT ION SELECTING THE BEYOND-USE DATE FOR NON-STERILE PREPARATIONS The beyond-use date (BUD) is the date or time after which the compounded product should not be used. The Study Tip Gal provides the default BUDs for non-sterile compounded preparations that are packaged in tight, light-resistant containers, per USP 795 standards. USP specifies refrigeration for water-containing oral formulations only. Individual products may have shorter stability and/or different storage requirements which will override USP-provided defaults. Other exceptions include: If any ingredient expires before the BUD, use the earlier expiration date. FORMULATION BEYOND-USE DATE Nonaqueous Formulations (e.g., a drug in petrolatum) Not later than 6 months (180 days). Store at room temperature. Water-Containing Oral Formulations (such as an oral suspension) Not later than 14 days when stored at controlled cold temperatures. Store in refrigerator. ----- .,A,,iA Not later than 30 days. Store at Water-Containing Topical/ Dermal and Mucosa! Liquid 1 room temperature. and Semisolid Formulations (such as a cream or lotion) I L_ BUDs can be extended if stability data is obtained that determines the drug is stable for a longer period. Beyond-Use Date Examples FORMULATION MAXIMUM BUD Metronidazole topical solution prepared with propylene glycol and distilled water Topical, aqueous 30 days Acetaminophen, diphenhydramine and hydroxyzine oral suspension prepared in lemon syrup (citric acid, purified water, lemon flavoring) Oral, aqueous 14 days, refrigerated Topical preparation of zinc oxide in white petrolatum Non-aqueous 180 days Nystatin in a strawberry-flavored popsicle with an 80% sorbitol and purified water solution Oral, aqueous Polymyxin and hydrocortisone prepared in a commercial emulsion cream for skin rash Topical, aqueous 30 days Topical, aqueous 30 days Estradiol powder, black cohosh powder and soybean oil preparation in hypromellose capsules Non-aqueous 180 days Morphine powder with stevia sweetener in a PEG lozenge Non-aqueous 180 days Progesterone suppository in an oleaginous base Non -aqueous Calamine powder prepared with glycerin in 70% isopropyl alcohol for poison ivy Topical, aqueous 30 days Lidocaine and diphenhydramine in poloxamer gel with lecithin/isopropyl palmitate Topical , aqueous 30 days Non-aqueous 180 days Topical, aqueous 30 days PREPARATION - - - - - - - - - - - - - --- Ciprofloxacin and dexamethasone in Versabase lotion Diclofenac powder in propylene glycol Lidocaine, alcohol USP and distilled water buccal dental gel Unit-Dose Repackaging A unit-dose refers to a small package that contains one dose of a medication. Unit-dose preparations can come from the manufacturer or a repackaging company, or a pharmacy can repackage multi-dose containers into unit-dose packages. Example: repackaging clopidogrel 75 mg from a multidose container of 100 tablets, with each unit-dose package containing one 75 mg tablet, which is the usual dose. 280 Unit-dose repackaging is not compounding, but shares some commonalities, including the assignment of a BUD, and safety requirements if repackaging HDs. BUDs for repackaged drugs should be the manufacturer's expiration date from the original container or 6 months from the repackaging date, whichever is earlier. J I l 180 days NON-STERILE QUALITY ASSURANCE A quality assurance (QA) plan outlines the steps and actions that ensure proper standards are maintained. It includes the Standard Ope1•ating Procedures (SOPs), which are itemized steps on how to perform routine and expected tasks. The QA plan must be reviewed and updated regularly. The QA program should include periodic testing of the finished compounded preparations. A pharmacy may do some QA testing in-house (e.g., confirming weight and consistency) and outsource others (e.g., sending products out to another company for sterility or stability testing). QA records need to include the names of the compounding staff, including their job orientation and training records.