PSCIG 1541L Pharmacy Compounding Lab 06 Fall 2024 PDF

PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Laboratory 06: Solutions Learning Objectives PERFORM calculations necessary to the preparation of solution dosage forms. ANALYZE the appropriateness of a prescribed product for a patient. S...

PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Laboratory 06: Solutions Learning Objectives PERFORM calculations necessary to the preparation of solution dosage forms. ANALYZE the appropriateness of a prescribed product for a patient. SELECT an appropriate vehicle for the preparation of a solution. PREPARE an electrolyte solution dosage form using a prepared syrup vehicle and appropriate flavoring. PREPARE a controlled substance solution dosage form using a co-solvent system. PACKAGE solutions within an amber prescription bottle. Pre-Laboratory Activities 1) Review the material provided below on Solution Dosage Forms and Labeling of Solution Preparations. Refer to Chapters 9 – 11 in Applied Pharmaceutics in Contemporary Compounding (Shrewsbury) or Chapters 15, 16, 17, 21, 22, and 27 in A Practical Guide to Contemporary Compounding (Elder) for more information. Solution Dosage Forms (USP Pharmaceutical Dosage Forms) Solution – a preparation that contains one or more dissolved chemical substances in a suitable solvent or mixture of mutually miscible solvents. Oral solutions are frequently sweetened and/or flavored to improve palatability and mask drug taste. Injectable and ophthalmic solutions must be sterile (see PSCIG 1542 – Winter Quarter) Vehicles for Solution Dosage Forms The vehicle (solvent) for a solution dosage form should be selected based on the route of administration and solubility of the drug(s). Remember: “like dissolves like” so polar solvents will dissolve polar solutes while less polar solvents will dissolve less polar solutes. The most common solvent is water (polar, nontoxic, inexpensive – water-based vehicles include syrups (e.g. Simple Syrup; OraSweet®) and suspending vehicles (e.g. methylcellulose; OraPlus®)) but other solvents may be used: Oral – alcohol,USP; glycerin; propylene glycol; oils Topical – acetone; isopropanol; polyethylene glycol; collodion; oils; polymers 109 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY The solubility of a drug should always be confirmed prior to preparation of a solution dosage form to ensure that a simple solution can be prepared. However, when a single solvent such as water will not solubilize a drug (e.g. a nonionic or less polar drug substance) then a change in pH (i.e. to shift the ionization status of the molecule) or a mixture of co-solvents of varying polarity may be used to improve solubilization. Co-Solvent Systems Development of a co-solvent system can be done experimentally by dissolving the solute in various concentrations of non-aqueous solvents (e.g. alcohol, USP or glycerin). For example, the solubility for phenobarbital in water is reported as being 1 g/1000 mL (or ~0.1%), which is significantly below the desired therapeutic concentrations. Therefore, solutions must be prepared using a co-solvent system. The following data have been reported to facilitate the preparation of phenobarbital solutions using a purified water/alcohol, USP/glycerin co-solvent system that has the appropriate solvating ability, safety, and viscosity. Phenobarbital Solubility in Water/Alcohol, USP/Glycerin Mixtures Glycerin (% (v/v)) 0 5 15 20 25 40 Phenobarbital Solubility (% (w/v)) Alcohol, USP (% (v/v)) 0.22 15 13 9 7 5 3 0.44 30 27 21 18 15 9 0.66 35 32 26 23 20 15 0.88 40 37 31 28 25 19 1.33 45 42 36 33 30 25 1.77 50 47 41 38 35 29 These data have been plotted for you on the following page. The graphs can be used to determine the specific amount of alcohol, USP needed to prepare water-based solutions at known phenobarbital and glycerin concentrations. For example, if a particular solution is to be prepared having a phenobarbital concentration of 1%(a), and a glycerin concentration of 25%(b), then an alcohol, USP concentration of approximately 26.5%(c) would also be needed to achieve the desired solubility (see graph). In addition, 2% is conventionally added to the needed alcohol, USP concentration to ensure solubility under all conditions. So, for the previous example, a solution having 28.5% alcohol (i.e. 26.5% + 2%) would actually be prepared. 110 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY 2.0 1.8 Phenobarbital Solubility (%) 1.6 1.4 1.2 (b) (a) 1.0 0.8 0% Glycerin 5% Glycerin 0.6 15% Glycerin 0.4 20% Glycerin 25% Glycerin 0.2 (c) 40% Glycerin 0.0 0 10 20 30 40 50 60 Alcohol, USP (%) Flavoring Oral Liquid Dosage Forms When flavoring liquid dosage forms such as solutions several factors must be accounted for including: Ability of the flavor to mask the drug Flavor to Mask Suggested Flavors Salty Cinnamon, raspberry, orange, maple, e.g. salts, especially low molecular weight butterscotch, licorice (glycyrrhiza), apricot, caramel Sweet Fruit, berry, bubblegum, vanilla e.g. Organic esters, alcohols, aldehydes Bitter Cocoa, chocolate, mint, cherry, walnut, licorice, e.g. nitrogen containing compounds e.g. alkaloids, free bases anise, raspberry, tutti-frutti, passionfruit of amides Sour/Acidic Fruit, citrus, cherry, raspberry e.g. acids and phenols Oily Wintergreen, peppermint oil, lemon, anise Metallic Mint, marshmallow Applied Pharmaceutics in Contemporary Compounding (Shrewsbury) Age of the patient (i.e. pediatric versus adult) o Pediatric patients: more sensitive to taste; prefer sweet flavors; dislike bitter flavors o Geriatric patients: decreased sense of taste and smell might require increased flavor 111 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Patient species (for veterinary products) Species Flavors Birds Grape, molasses, orange, pina colada, tutti-frutti, other sweet flavors Cats Beef, butterscotch, cheese, chicken, liver, molasses, peanut butter, salmon, sardine, tuna Dogs Beef, cheese, chicken, liver, marshmallow, peanut butter, raspberry, strawberry Horses Alfalfa, apple, bluegrass, caramel, cherry, molasses, clover Ferrets Fish, fruits, molasses Gerbils, iguanas, rabbits Fruits, vegetables Applied Pharmaceutics in Contemporary Compounding (Shrewsbury) Stability of the product upon addition of flavoring (e.g. consider the co-solvent system above) The pharmaceutical elegance of the product can also be increased by including coloring that matches the flavor of the final product (e.g. yellow for lemon, purple for grape). As with flavors, check the stability of the color with the product. Taste masking may be improved by including viscosity enhancing agents such as methylcellulose (e.g. OraPlus®) Labeling of Solution Preparations Directions for use (appropriate verb) - “Give/Take…orally…” used for oral solutions - “Apply…(indicate “to the affected area”/”vaginally”/”rectally”…)…” used for topical solutions - “Use…” for solutions administered “as a shampoo/soak/douche/etc.” - “Place/Instill…(indicate route of administration)…” for nasal and otic (or ophthalmic – to be covered in PSCIG 1542) solutions Expression of active ingredient concentration - Oral: express as a metric weight or metric volume per volume to be administered (e.g. 50 mg/5 mL) o NOTE: electrolyte dosage should be expressed as BOTH the milliequivalent AND metric weight (e.g. 8 mEq (50 mg)/5 mL) - Topical/Nasal/Otic: express as a percent concentration (e.g. 10%) - If Alcohol, USP is used as an excipient, its %(v/v) concentration within the final product must be expressed on the prescription label. Auxiliary Labeling - If not dispensed in a tight container having a safety closure: 112 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY - Even when preserved, oral solutions should be stored under refrigeration, unless contraindicated* *possible contraindications include solutions near their saturation point, having a high viscosity, and/or containing drug(s) that are unstable at low temperatures. - If the prescription is intended for non-oral administration, it should contain one of the following labels indicating the appropriate route of elimination. Dispense solutions in an (appropriately sized) amber bottle or other packaging device appropriate for the application (e.g. unit dose oral syringes, nasal or topical spray bottles, etc.). 113 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY 114 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Name: __________________________ Seat # _______-A Laboratory 06: Pre-Laboratory Assessment CASE #1 You prepare the following formulation: Rx : Phenobarbital 40 mg/5 mL Glycerin 13.5 mL M.ft. 3 fl.oz. sol. 1. What is the primary purpose of the glycerin in the formulation? (a) Sweetener (has a sweet taste but not the primary purpose) (b) Viscosity enhancer (is viscous but not the primary purpose) (c) Cosolvent (d) Flavoring (not used as a flavoring) 2. When labeling this product, which of the following is most appropriate? (a) Phenobarbital 40 mg/5 mL, Glycerin 13.5 mL Solution (b) Phenobarbital 0.8%, Alcohol, USP 31.5% Solution (c) Phenobarbital 8 mg/mL, Alcohol, USP 31.5% Solution (d) Phenobarbital 40 mg/5 mL, Glycerin 15%, Alcohol, USP 31.5% Solution (e) Phenobarbital 40 mg/5 mL, Alcohol, USP 31.5% Solution Glycerin not needed on label; drug expressed as metric unit per metric volume relative to the dose, alcohol, USP (as percentage strength) should be on the label. SORRY I MISSPOKE IN PRELAB – ANSWER SHOULD BE (E) NOT (D) SINCE GLYCERIN DOES NOT NEED TO BE ON THE LABEL. GAVE HALF CREDIT FOR (E). 115 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY over  CASE #2 You need to prepare an oral sodium chloride electrolyte solution as follows: Rx : NaCl 23.4% (w/v) Flavor q.s. M.ft. 60 mL sol 3. Which of the following flavors might best mask the NaCl? (a) Tutti-Frutti (mixed tropical fruit) (b) Caramel (c) Mint (d) Marshmallow See the flavor information above 4. When labeling this product, which of the following expressions is most appropriate? (a) NaCl 23.4% Solution (b) Sodium Chloride 23.4% Solution (c) NaCl 1170 mg (20 mEq) Solution (d) Sodium Chloride 1170 mg/5 mL (20 mEq/5 mL) Solution (e) Sodium Chloride 1170 mg (20 mEq)/teaspoonful Solution Spell out NaCl and express as both the metric (mg) and mEq dose per metric volume given. Dosage form should be indicated. 5. You dispense the product in a 2 fl.oz. amber prescription bottle that has a safety closure. Which of the following accessory labels is required on the bottle? (a) Refrigerate (b) Shake Well solutions do not need to be shaken (c) Keep Out of Reach of Children bottle has a safety closure (d) Compounded for You 116 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Laboratory 06: Solutions Laboratory Assignment Complete the following activities related to compounding solution preparations. CASE #1 – Preparation of an Electrolyte Solution COLLECT Case: CK is a 6 y.o. female patient suffering from short term hypokalemia. The patient has also been diagnosed with phenylketonuria. Additional Information: The molecular formula, molecular weight, and water solubility for potassium chloride (available as a bulk powder) can be found in Remington or other appropriate scientific references. Prescription: Robert Holden, M.D. 1994 Gotham Way, Gotham City, AZ 85359 Ph: 580-590-1994 Name: Celina Kyle Date: 10/8/24 Address: 643 N. 67th Ave., Glendale, AZ 85308 KCl 5 mEq/tsp Flavored syrup q.s. M.ft. sol. ii fl.oz. Sig: ii tsp t.i.d. pc w/ aq Refill 5 times Dispense as Written Substitution Permissible DEA#__________________ DEA# 117 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY ASSESS 1. Is the prescribed route of administration and dosage form appropriate for this patient? What are some of the disadvantages of this dosage form? Oral administration is the most convenient and natural route of administration and, since the patient is only 6 years old, a liquid dosage (e.g. solution) form would be preferred over a solid dosage form (e.g. capsule or tablet) for ease of swallowing. However, bulk solution dosage forms may have some disadvantages including: (1) dosing may be more inconvenient and/or inaccurate since the caregiver needs to measure the appropriate dose; (2) taste masking may be more difficult since the solutes more readily contact the taste buds; (3) stability may be decreased due to the water content in the product (syrups, by definition, are aqueous solutions) requiring a shorter beyond use date (BUD) and storage under refrigeration. 2. Why does the potassium chloride solution need to be taken with water? Potassium chloride is very irritating to the GI lining and concentrated solutions may cause irritation/ulceration, even after meals, if not diluted upon administration. Note: this is particularly a concern with the solid dosage forms which are more concentrated and must be taken with plenty of water especially because, if the product were to lodge in the esophagus, the potassium chloride could cause esophogeal ulceration. Reference: Facts and Comparisons [online database] available at http://fco.factsandcomparisons.com PLAN 3. Preparation of a Flavored Syrup Vehicle You do not have any syrup vehicle on hand and therefore need to prepare one in advance of making the final product using the following formulation: Flavored Syrup Vehicle Sucrose 600 g 600 𝑔 𝑥 75 𝑚𝐿 = 45 𝑔 Flavor q.s. 1000 𝑚𝐿 Purified water q.s. a.d. 1 L Complete the compounding steps for the preparation of 75 mL of the syrup vehicle: (a) Weigh 45 g of sucrose using an electronic balance and place into a 125-mL conical graduate. (Hint: tare the conical graduate on your balance and weigh the sugar directly into the graduate) 118 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Note: conical graduates are preferred over cylindrical graduates for ease of preparation; however, measurements in these graduates are prone to greater error due to their larger diameters (see lab #2). (b) Add small portions of purified water up to approximately 70 mL while stirring in order to dissolve all of the sucrose. Note: do not stir too vigorously, especially as the viscosity increases, as small air bubbles may become trapped in the solution leading to measurement error and/or difficulty in assessing the dissolution of the sucrose. We do not QS up to the total volume at this point in order to leave room for the addition of flavors. (c) Add X drops or X mL of flavoring (flavor: varies) (d) QS up to 75 mL with purified water. (e) Transfer the syrup to a 100-mL beaker and save for use in preparation of the prescription. 4. Indicate a use for all of the ingredients in the prescribed formulation, including those used to prepare the flavored syrup vehicle. Ingredient Use Sucrose Taste masking / improve palatability (sweetener and viscosity enhancer) Water Solvent / vehicle Flavoring Taste masking / improve palatability / pharmaceutical elegance Potassium chloride Treatment of hypokalemia (low blood levels of potassium) 5. Complete the COMPOUNDING LOG for the preparation of the product: COMPOUNDING LOG Preparation: Potassium 5 mEq/5 mL Solution Date Prepared: 10/09/24___ ______ Patient Name: Celina Kyle Prescriber: Robert Holden, M.D. Prescription Number: e.g. 01-A_____________________ Prepared by: initials ___ Calculations: (note: generally no additional overage is needed in compounding solutions) 5 𝑚𝐸𝑞 1 𝑡𝑠𝑝 5 𝑚𝐸𝑞 KCl 𝑡𝑠𝑝 𝑥 5 𝑚𝐿 = 5𝑚𝐿 (note: for the label this converts to 10 mEq/10 mL) 5 𝑚𝐸𝑞 30 𝑚𝐿 5 𝑚𝐿 𝑥2 𝑓𝑙. 𝑜𝑧. 𝑥 𝑓𝑙.𝑜𝑧. = 60 mEq MW of KCl = 74.5 g/mole; valence = 1 (KCl → 1K+1 + 1Cl-1) therefore the milliequivalent weight of 𝑀𝑊 74.5𝑚𝑔/𝑚𝑚𝑜𝑙 KCl is 𝑣𝑎𝑙𝑒𝑛𝑐𝑒 = 1 𝑚𝐸𝑞/𝑚𝑚𝑜𝑙 = 74.5 𝑚𝑔/𝑚𝐸𝑞 119 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY 74.5 𝑚𝑔 4470 𝑚𝑔 745 𝑚𝑔 60 𝑚𝐸𝑞 𝑥 𝑚𝐸𝑞 = 4470 𝑚𝑔 (note: for the label this converts to 60 𝑚𝐿 𝑥 10 𝑚𝐿 = 10 𝑚𝐿 ) Compounding Procedure: a. Weigh 4470 mg (4.47 g) of potassium chloride on an electronic balance. Based on the reported water solubility of potassium chloride, do you expect the prescribed concentration to be soluble in the syrup vehicle? It is good practice to confirm the water solubility of a substance before preparing a solution. In this case, the reported water solubility of KCl is 1 g/2.8 mL. Therefore, we will need: 4.47 g KCl 2.8 mL water =12.5 mL water 1 g KCl We are making 60 mL of solution. Although some of the water in the syrup is taken up by the sucrose (based on the solubility of sucrose, approximately 45 g x 0.5 mL/g = 22.5 mL), we should have sufficient water remaining in our syrup solution for the KCl to dissolve. b. Place the potassium chloride into a 125-mL conical graduate. c. Add a small portions of the syrup vehicle (flavor: to be determined in lab) up to approximately 50-55 mL while dissolving all of the potassium chloride. Note: feel free to taste a small amount of your final product (use your stirring rod to let a small drop fall onto your finger) to see how well your flavor choice masked the saltiness of the potassium chloride. Adjust flavoring if desired before the final QS but ensure you update your documentation. d. QS with syrup vehicle (flavor: to be determined in lab) to 60 mL. e. Dispense in a 2 ounce amber prescription bottle and with an appropriate dispensing device (Note: we will not be ‘dispensing’ a device in lab). BUD: 14 days (10/23/24) Storage: Room Temperature / Refrigerated / Frozen Quality Control: visual inspection of uniformity (free of undissolved material, correct volume); pharmaceutical elegance of solution (appropriate flavor) and packaging (no product on the outside of the bottle or on label; label is straight/not wrinkled; at least one graduation on the side of the bottle should be visible) IMPLEMENT 6. Complete the documentation of the compounding of the preparation by recording pertinent information on the BACK OF THE PRESCRIPTION (lot, manufacturer and expiration dates will be available in lab): BACK OF THE PRESCRIPTION 120 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Sucrose Flavor (if multiple used list all) Potassium chloride Rx# e.g. 01-A Mfg Mfg Mfg 10/09/24 Lot# Lot# Lot# Initials Exp Exp Exp Complete the PRESCRIPTION LABEL and indicate any ACCESSORY LABELS you would apply to the final dispensed product. Celina Kyle both mg and mEq dose needed for electrolytes; express conc. Potassium chloride 10 mEq (745 mg) / 10 mL Solution in terms of the volume the patient takes for the dose Give 10 milliliters by mouth after breakfast, lunch, and dinner with a glassful of water. use #’s not words; be specific with what “tid” means Do not use beyond: 10/24-25/23 14 days (water, unpreservd) Refills: 5 Rx#: e.g. 01-A Filled on: 10/23/24 Quantity: 60 mL Prescribed by: Robert Holden, M.D. for bulk products include the units with quantity MWU-CPG Pharmacy Teaching Lab 19555 N. 59th Ave., Glendale, AZ 85308 Phone: (623) 123-4567 Accessory Labels: (if no safety closure) FOLLOW UP 7. If upon follow up it was discovered that the patient was diabetic and the sucrose content was an issue, which sweetener(s) could be used to prepare an alternative product? Artificial sweeteners such as sucralose, stevia, saccharin sodium, and aspartame do not increase blood glucose levels (i.e. they are non-glycogenic) and may be used for diabetic patients. However, our patient also suffers from phenylketonuria (PKU) which is a genetic disorder in which a patient cannot metabolize phenylalanine, resulting in brain damage, intellectual disabilities, behavioral symptoms, or seizures. Aspartame contains phenylalanine and thus should not be used in this patient. Example: Note: sugar alcohols (e.g. sorbitol) are less glycogenic than sucrose but may still cause modest increases in blood glucose levels. 121 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY CASE #2 – Preparation of a Solution Using a Co-Solvent System COLLECT Case: WS is a 56 y.o. male suffering from insomnia. Additional Information: Phenobarbital is available as a bulk powder and is a controlled substance (C-IV). Prescription: Nick Riviera, D.O. 1987 Ullman Street Springfield, AZ 85123 Ph: 602-765-4321 Name: Waylon Smithers Date: 10/07/24 Address: 1989 Springfield, AZ 85123 Phenobarbital 75 mg/5 mL Glycerin 15% Purified water qs 60 mL M.ft. sol. Sig: 1 Tbsp hs Refill 0 times Dispense as Written Substitution Permissible DEA#__________________ DEA# 8. In which route(s) of administration and dosage form(s) is phenobarbital commercially available? What are the common use(s) for phenobarbital? Route(s): oral parenteral Dosage Form(s): tablet, solution(elixir) solution Common Use(s): seizures; sedation** **Note: phenobarbital may no longer be recommended for the treatment of insomnia; however, we will assume the intent has been confirmed with the prescriber upon discussing the need for a compounded product Reference: Facts and Comparisons [online database] available at http://fco.factsandcomparisons.com 122 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY ASSESS 9. Is the prescribed product more appropriate for this patient than the commercially available products? Why or why not? Among the available routes of administration, only the oral tablet and solution would be applicable as parenteral administration is usually limited to institutional (hospital) use. The patient has no difficulty swallowing, so either the tablets or solution would be potential options. However, given the prescribed dose (225 mg) none of the available product strengths (20 mg/5 mL elixir; 15 – 100 mg tablets) would be ideal. Reference: Facts and Comparisons [online database] available at http://fco.factsandcomparisons.com PLAN 10. Complete the COMPOUNDING LOG for the preparation of the product: COMPOUNDING LOG Preparation: Phenobarbital 75 mg/5 mL Solution Date Prepared: 10/09/24 Patient Name: Waylon Smithers Prescriber: Nick Riviera, D.O. Prescription Number: seat-section (e.g. 01-A)____________ Prepared by: initials ____ Calculations: (note: generally no additional overage is needed in compounding solutions) 75 𝑚𝑔 Phenobarbital 𝑥 60 𝑚𝐿 = 900 𝑚𝑔 5 𝑚𝐿 75 𝑚𝑔 𝑤 5 𝑚𝐿 𝑥 100 𝑚𝐿 = 1.5% ( 𝑣 ) 𝑓𝑜𝑟 𝑢𝑠𝑒 𝑖𝑛 𝑑𝑒𝑡𝑒𝑟𝑚𝑖𝑛𝑖𝑛𝑔 𝑐𝑜 − 𝑠𝑜𝑙𝑣𝑒𝑛𝑡𝑠 15 𝑚𝐿 Glycerin: 𝑥 60 𝑚𝐿 = 9 𝑚𝐿 100 𝑚𝐿 Alcohol, USP: Using the co-solvent chart read from 1.5% phenobarbital on the Y-axis across to the 15% glycerin line. Then read down to the X-axis to determine the concentration of Alcohol, USP = ~38%. Add 2% to ensure solubility: 38% + 2% = 40% 40 𝑚𝐿 100 𝑚𝐿 𝑥 60 𝑚𝐿 = 24 𝑚𝐿 Compounding Procedure: a. Weigh 900 mg (0.9 g) of phenobarbital on an electronic balance. b. Place the phenobarbital into a 125-mL conical graduate. c. Measure 24 mL of alcohol, USP using a 25 mL cylindrical graduate. 123 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY d. Measure 9 mL of glycerin using a 25-mL cylindrical graduate. e. Add the alcohol, USP and dissolve a majority of the phenobarbital. f. Add the glycerin and dissolve any remaining phenobarbital. g. QS with small portions of purified water to a final volume of 60 mL. h. Dispense in a 2 ounce amber prescription bottle and with an appropriate dispensing device (Note: we will not be ‘dispensing’ a device in lab). BUD: 35 days for preserved aqueous (11/13/24) Storage: Room Temperature / Refrigerated / Frozen Quality Control: visual inspection of uniformity (free of undissolved material, correct volume); pharmaceutical elegance of solution (appropriate flavor) and packaging (no product on the outside of the bottle or on label; label is straight/not wrinkled; at least one graduation on the side of the bottle should be visible) 11. What are the advantages and disadvantages of each of the solvents used in this product? Purified water – most common and least toxic solvent; however, phenobarbital has a relatively low ‘polarity’ and thus has a relatively poor water solubility. Water also creates significant stability concerns. Alcohol, USP – less polar than water so better for dissolving less ‘polar’ solutes such as phenobarbital, may act as a preservative. However, it may cause disulfram-like reactions with certain medications and it has its own pharmacological effects that may present possible safety concerns. Glycerin – also better than water at dissolving less ‘polar’ solutes such as phenobarbital, which enables a lower alcohol content. Glycerin may also act as a preservative, and has a sweet taste and a relatively high viscosity, which may help taste-masking. However, the relatively high viscosity may also make accurate dosing more difficult and slows drug dissolution, which increases preparation time. IMPLEMENT 12. Complete the documentation of the compounding of the preparation by recording pertinent information on the BACK OF THE PRESCRIPTION: BACK OF THE PRESCRIPTION Rx# e.g. 01-A 10/09/24 Initials Phenobarbital * Mfg Lot# Exp (Ethyl) Alcohol, USP Mfg Lot# Exp Glycerin Mfg Lot# Exp *CONTROLLED SUBSTANCES LOG: Used: 900 mg 124 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Dispensed: 900 mg Discarded: 0 mg Complete the PRESCRIPTION LABEL and indicate any ACCESSORY LABELS you would apply to the final dispensed product. Waylon Smithers Phenobarbital 225 mg/15 mL Solution express conc. in terms of the actual volume the patient takes Alcohol, USP 40% must have “,USP” to indicate it is ethyl alcohol Take 15 milliliters by mouth at bedtime. remember to use #s instead of words; spell out mL 35 days for preserved aqueous products Do not use beyond: 11/13/24 (alcohol acts as both cosolvent and Refills: 0 preservative) Rx#: e.g. 01-A Filled on: 10/09/24 Quantity: 60 mL Prescribed by: Nick Rivera, D.O. for bulk products include the units with quantity MWU-CPG Pharmacy Teaching Lab 19555 N. 59th Ave., Glendale, AZ 85308 Phone: (623) 123-4567 Accessory Labels: (if no safety closure) FOLLOW UP 13. The patient calls the pharmacy the following day to inquire if the medication can be diluted in a small amount (i.e. and equal volume) of either water or orange juice to improve taste. Determine if the phenobarbital would remain soluble after dilution. By adding an additional 15 mL of another liquid such as water or juice, the overall volume of the dose would double while the final concentrations of all of the components would be reduced to half of the original strength: Phenobarbital 1.5%/2 = 0.75% Glycerin 15%/2 = 7.5% Alcohol, USP 40%/2 = 20% Looking at the co-solvency data, a new concentration of 0.75% phenobarbital at a glycerin concentration of 7.5% would require ~31% alcohol, USP. With only 20% alcohol, USP in the diluted dose, the phenobarbital would likely not remain fully soluble. Additionally, using a liquid other than water, such as orange juice, increases the uncertainty of solubility as there are additional chemicals (e.g. Vitamin C) and properties (e.g. acidity) that are introduced. Knowing that phenobarbital is also available as a sodium (a cation) salt, the drug itself must be a weak acid (the anion) that would exist in the following equilibrium: HP  H+ + P- (HP) free acid; (H+) hydrogen ion; (P-)ionized form Additional hydrogen ions from the acidic orange juice would shift the equilibrium to the left, increasing the fraction of the unionized (i.e. the uncharged, lower polarity and hence unsolubilized) free acid even further. 125 PSCIG 1541L: Pharmacy Compounding Laboratory 06 – Fall 2024 – KEY Therefore, the patient should be advised not to dilute the dose. If taste is an issue, the product may be reformulated with flavors and/or sweeteners to improve palatability. 14. The patient returns to the pharmacy with a new prescription for “Phenobarbital 75 mg/5 mL Alcohol-Free Solution.” How can the product be compounded to meet the new requirement? The new prescription requires that the product now be alcohol-free. Therefore, if the amount of alcohol in the product is decreasing then then amount of other co-solvents (glycerin and/or water). Looking at the co-solvent chart, even with the highest concentration of glycerin (40%) alcohol, USP (~25%) is still needed to prepare the 1.5% (w/v) solution of phenobarbital. Options for decreasing the alcohol, USP concentration further might be: (a) increase the concentration of glycerin further. However, given the chart even high concentration of glycerin require a large amount of alcohol, USP as a cosolvent for 1.5% phenobarbital; (b) decrease the concentration of phenobarbital in the solution. This might be successful if the glycerin concentration was increased. However, we would need to test the formulation to ensure that the drug is soluble. Additionally, the patient is already taking 15 mL of the solution and decreasing the phenobarbital concentration would likely result in an inconvenient dosing volume (e.g. at 0.2% phenobarbital the patient would need to take 112.5 mL for the 225 mg dose); (c) change the form of the drug to phenobarbital sodium. Salt forms of drugs are much more soluble in an aqueous environment (e.g. water solubility for phenobarbital sodium is 100 mg/mL and therefore