PHAR 434: PHARMACEUTICS IV Non-Sterile Practical

SEMISOLIDS Topicals Suppositories Troches

Bases: Every product has a base as its major component. The base defines the objective of the product – its purpose. The drug is carried within the base, similar to the vehicle of a liquid.

- Ex: Dry Skin Condition – Oleaginous Base - Ex: Treatment of Acne – Aqueous Base, or O/W Base

‘Ointment’ Base Oleaginous, Absorption, W/O + Water, Water-Washable, O/W, Aqueous

Suppository Base Fatty, W/O, PEG, Glycerinated Gelatin

Troche Base Chewable (Glycerinated-Gelatin), Soft (PEG, Choco), Hard (Sugar)

(1): TOPICALS Topical Bases: The ointment bases below are listed in order of decreasing hydrophobicity, increasing hydrophilicity

Ointment Base Definition Levigating Agent Oleaginous Ex: Petroleum- pure hydrocarbon

Greasy, non-washable, essentially pure oil They prevent moisture loss, occlusive!

Mineral Oil

Absorption Ex: Aquaphor, Aquabase

Greasy, non-washable, with added surfactants but essentially no water (~W/O). Allows small quantities of aqueous solutions to be incorporated into ointment bases

Mineral Oil

W/O Ex: Eucerin

Moderately greasy, moderately washable. Involves water added to an absorption base

Mineral Oil

Water-Washable Ex: Polyethylene Glycol (PEG)

Not greasy, water-washable, it is water-soluble Propylene glycol or glycerin

O/W Ex: Vanicream, Hydrophilic Ointment

Essentially aqueous, not greasy, and totally washable. It is a vanishing cream

Glycerin

Aqueous Ex: Methylcellulose or carbomer gel

Pure hydrophilic. As water-soluble as it gets Glycerin

Levigating Agents: Levigating agents must be compatible with the ointment base when preparing creams, ointments, lotions, and sticks. Review the previous chart to find the appropriate levigating agent for your base. In general, mineral oil goes with our hydrophobic/oleaginous bases such as in Ointments, whereas glycerin goes with our hydrophilic/aqueous bases such as in creams or gels.

OIL Non-Polar

WATER Polar

Petrolatum

Ointment

Beeswax Methylcellulose

Gel

Semi-polar Glycols

A Q U E O U S (Creams) O L E A G I N O U S

Aquaphor Hydrophilic Ointment

PEG, Polybase

O/W Water-Soluble Base

Contents Ointments and creams: Pages 1-2 Sticks: Pages 3-4 Lotion: Page 3 Suppositories: Pages 5-6 Troches: Pages 7-9

PREP: Ointments While ‘ointment’ refers to any topical on the oil-water spectrum, ointment formulations specifically relate to the oil-soluble half of the spectrum. Ointments are generally applied to dry scaly skin. Ideal Base: Petrolatum Levigating Agent: Mineral Oil *Supporting Agent: Aquaphor (W/O+Surfactants)

PREP: Cream Creams are on the aqueous half of the spectrum. They are usually applied to weeping or oozing surfaces. Ideal Base: Hydrophilic Ointment –or- Polybase Levigating Agent: Glycerin

Equipment Needed

- Electronic Balance: Make sure you level your balance - Pill Tile: This is where you levigate your drug - If trituration is required – Glass pestle and mortar - Rubber spatula – This is used for the quantitative transfer, as well as removal from glass mortar - Ointment jar – for the final product

Ointment/Cream Procedure

1. Weigh your ingredients and label them. Do not leave powders laying around unmarked. a. Base b. Drug c. *Aquaphor if needed for Ointments. It may be needed to incorporate small quantities of aqueous solutions

to ointment bases, such as urea. 2. Levigate your drug with an appropriate levigating agent on a pill tile

a. Ointment product: Use mineral oil to levigate your drug on a pill tile i. *Exception: Water soluble drug – Dissolve drug minimally in water, mix with aquaphor

b. Cream product: Use glycerin to levigate your drug on a pill tile 3. Geometrically mix your base into your drug

a. Look at your drug. How much is there. Mix an equal amount of your base to homogeneity on the pill tile. b. How much is there now? Mix an equal amount of your base to homogeneity on the pill tile. Continue.

4. Transfer your compounded product to an ointment jar a. If you get your jar greasy/wet/whatever, use isopropyl alcohol to wipe it down

5. Quality Check

Quality Control: Color uniformity, Grittiness check, Weight/volume, appearance, odor, viscosity, particle size distribution, and texture, Field test = rub it on yourself as the grittiness check Counseling: For external use only, store in a cool dry place, keep tightly closed, keep out of reach of children, monitor for adverse/allergic reaction. Calculation Example

Drug Source = Pure Drug Suppose we need 0.1mg/g of Drug Cream, total 2 Oz 1: How much drug do we need? 2 Oz = 60g 0.1mg/g * 60g = 6mg of drug is needed We cannot weigh 6mg on our electronic balance, but we can weigh 40mg. This is the least weighable quantity (LWQ) 2: !"#$&''('(

)*+= -./01!"#$

-./01!"#$2!34#'5/ à 67$

897$= 897$

:

So X = 266mg. Subtract the Batch Drug = 226mg diluent 3: Weigh 40mg drug, label. Weigh 226mg diluent, label. 4: Geometrically mix. If you need colored lactose, do it. 5: Weigh 40mg of your final product, it will have 6mg of your drug.

Drug Source = Salt, or Commercial Product Ex: Caffeine Citrate Powder, the amount you weigh will not be the amount of caffeine you have. Must account for the molecular weight of citrate.

𝐶𝑎𝑓𝑓𝑒𝑖𝑛𝑒𝑀𝑊𝐶𝑎𝑓𝑓𝑒𝑖𝑛𝑒𝐶𝑖𝑡𝑟𝑎𝑡𝑒𝑀𝑊

=𝑇𝑜𝑡𝑎𝑙𝐶𝑎𝑓𝑓𝑒𝑖𝑛𝑒𝑁𝑒𝑒𝑑𝑒𝑑

𝐶𝑎𝑓𝑓𝑒𝑖𝑛𝑒𝐶𝑖𝑡𝑟𝑎𝑡𝑒𝑡𝑜𝑤𝑒𝑖𝑔ℎ

Ex: Captopril 12.5mg tablets, the tablet weighs much more than 12.5mg. Must do a conversion! Assume Rx needs 30mg 1: Determine how many tablets you need: 30mg/12.5mg = 3 tablets 3 tablets has 37.5mg drug. We do not need all of it. 2: Find out how much 3 tablets actually weighs, lets pretend 120mg

37.5𝑚𝑔𝑐𝑎𝑝𝑡𝑜𝑝𝑟𝑖𝑙120𝑚𝑔𝑡𝑜𝑡𝑎𝑙𝑤𝑒𝑖𝑔ℎ𝑡

=30𝑚𝑔𝑐𝑎𝑝𝑡𝑜𝑝𝑟𝑖𝑙𝑛𝑒𝑒𝑑𝑒𝑑

𝑋𝑡𝑟𝑖𝑡𝑢𝑟𝑎𝑡𝑒𝑑𝑝𝑜𝑤𝑑𝑒𝑟𝑛𝑒𝑒𝑑𝑒𝑑

3: Triturate and weigh out your powder. X = 96mg

PREP: Lotion A lotion is made by diluting your base with compatible diluent. Lotion are usually applied to rubbing areas with friction. Lotion formulations are characterized by viscosity, not polarity. Therefore, a lotion may be either oil-based or water-based, and will be made to less viscous via dilution.

- Hydrophobic Base (ie Aquaphor, Petrolatum): DILUTE with mineral oil - Hydrophilic Base (ie Methylcellulose): DILUTE with water or glycerin - For lotions we are diluting our base to the desired viscosity – recall lotions are characterized by viscosity. So we

will continue adding drops of mineral oil to petrolatum in the case of an oil-based lotion until we reach the desired viscosity.

Lotion Procedure Methylcellulose formulation

1. Weigh your ingredients and label them - Methylcellulose (I recommend 2%) - Drug 2. Levigate/Dilute your Methycellulose with

Glycerin (Add water?) 3. Levigate your drug with glycerin in a mortar 4. Geometrically add your base to your drug

Ointment Base formulation 1. Weigh your ingredients and label them - Aquaphor - Drug 2. Dilute the Aquaphor with mineral oil 3. Levigate your drug with mineral oil in a mortar 4. Geometrically add your base to your drug

Quality Control: Pourable (squeezable if in bottle), Qs volume, grittiness check Counseling: For external use only, shake well, store in a cool dry place, keep tightly closed, keep out of reach of children, monitor for adverse/allergic reaction. Stick dosage forms are made by adding thickening agents to the ointment base. You’ll need to refer to a book to find the formula. PREP: Hydrophobic Stick Hydrophobic Stick Formulation: This product is compounded by melting hydrophobic ingredients on a water bath, adding drug and other ingredients after the wax has melted, and pouring into the stick device. Ingredients that are heat sensitive or volatile are added after melting of base ingredients to minimize ingredient loss. The benefits of the hydrophobic formulations include the formation of a barrier to prevent moisture loss

- Hydrophobic Base (ie Petroleum) à Add Beeswax or high-melting point wax Hydrophobic Stick Procedure [Heat source, evaporating dish

- Weigh your ingredients and label them. Do not leave powders laying around unmarked. o Base: Usually petrolatum o Emulsifying agent: Beeswax - excellent agent for emulsifying water-soluble components with the base o Thickening agent: Stearic acid? o Stearyl alcohol? o Drug - In class we used camphor, menthol

- Combine and melt your hydrophobic ingredients on a heated water bath o This often includes Petrolatum, Stearic acid, stearyl alcohol, and beeswax

- Remove from heat, add in your drug. Stir to dissolve until homogenous - While still warm, pour into application devices, slightly overfilling each tube. Try to work quickly and effectively - When the surface of the stick has hardened, add cap - Store devices upright for 24 hours until completely hardened. - Label, dispense, and counsel

Quality Control: Allow remaining melted formulation to cool in small evaporating dish for thorough evaluation. Evaluate the cooled medicated sticks before dispensing. Counseling: For external use only, store in a cool dry place, keep tightly closed, keep out of reach of children, monitor for adverse/allergic reaction.

PREP: Hydrophilic Stick The most common example of a hydrophilic stick is deodorant. Similar to the hydrophobic stick, this product is compounded first by heating the ingredients until fully dissolved, adding the drug, pouring and cooling it in the application device. Be wary of ingredients that are heat sensitive, such as methyl salicylate, a common ingredient in the IcyHot stick. There are a few candidate bases, the one used in class involved propylene glycol and sodium stearate

- Hydrophilic Base à Propylene Glycol + Sodium Stearate when heated and mixed forms a gel. - Hydrophilic Base (ie PEG) à Add Sodium Stearate

Equipment needed Hot plate beaker water for boiling evaporating dish glass stirring rod And yea some other stuff. Check procedure Hydrophilic Stick Procedure - The following is a paraphrased protocol from Dr. Pluta’s Semisolid lab -

- Weigh/Measure your ingredients and label them. Do not leave powders laying around unmarked. o Base: In this case we will use Propylene glycol and Sodium Stearate o Drug o Since liquids are involved, knowing the density will be critical for determining appropriate content. o Ingredients: Methyl salicylate, menthol, sodium stearate, propylene glycol, purified water

- Set up your evaporating dish on top of a boiling beaker-hot plate - Add propylene glycol and purified water to the already hot evaporating dish, mix using a stirring rod.. - Add sodium stearate to this mixture and mix thoroughly using a stirring rod.

o Using a thermometer, make sure the temperature does not exceed 75º C. The goal is to have the sodium stearate completely dissolved/melted, which should occur between 55-70º C.

- Once the sodium stearate is completely dissolved, remove the evaporating dish. If excessively hot, allow to cool until < 75ºC

- Triturate menthol in a different evaporating dish to reduce particle size. - Add the crushed menthol to the sodium stearate/propylene glycol/water system and mix to dissolve. - Add methyl salicylate to the mixture, mix to dissolve

o If your mixture is too hot, the methyl salicylate may burn and turn orange - Allow the preparation to cool, but before it hardens – pour it into a 20g application stick

o Retain excess for QC evaluation - After filling, place the application stick into the freezer for cooling and hardening - Cap the stick after hardening is underway or complete. - The finished stick should be solid and an opaque white. If orange, you fucked up. But you still have time, try

again. Quality Control: Allow remaining melted formulation to cool in small evaporating dish for thorough evaluation. Evaluate the cooled medicated sticks before dispensing. Counseling: For external use only, store in a cool dry place, keep tightly closed, keep out of reach of children, monitor for adverse/allergic reaction.

(2): SUPPOSITORIES Suppositories can be very relaxing to make. Heating, casting, cooling Suppository Bases: Fatty, W/O, PEG, Glycerinated Gelatin

Name Utility Pharmaceutics Yea what? Lubricant Polybase (Perrigo) Dissolve

Inactive Water-soluble ointment base (PEG is another!)

Used in suppositories. Mixture of MW polyethylene glycol and polysorbate

Light Mineral Oil or Vegetable Oil Spray

Fattyblend (Fagron) Melt

Inactive Water-insoluble suppository base

Serves as the alternate suppository base of cocoa butter. Homogenous mixture of triglycerides

Glycerin

Glycerinated-Gelatin

Inactive Hydrophilic base, suppository base

Homogenous mixture of glycerin, gelatin, and water **Special mixing instructions, see end of this section

Light mineral oil or vegetable oil spray

- Fatty: Oleaginous. Such as Cocoa Butter, or fattyblend. Designed to melt at body temperature - PEG: Specific Polyethylene Designed to dissolve at body temperature, such as vaginal suppositories - Glycerinated Gelatin: Aqueous. Has a laxative side effect, as glycerin is an irritant.

Lubricating Agents: Suppository mold lubricants should be opposite polarity to the suppository formulation to facilitate the removal of the suppository from the mold. See procedure below for examples. Calculations

- For the most part, we will be using solids, weighing them, and turning them into a product that has a set volume. Therefore, knowing the suppository mold volume is 2mL (rectal), determine the density of your base so you know how much of it to weigh for the full prep.

Approach - (1) Determine the suppository base Base should be opposite polarity of the active drug - (2) Determine the appropriate lubricant Lubricant should be opposite polarity of the base. - (3) Determine the appropriate levigating agent Levigating agent should be same polarity as base. - (4) Determine the objective of the drug Will it be melting or dissolving? Is the drug heat sensitive? - (5) Is this a high drug dosage? A high drug dose is ³ 30% of the suppository weight or volume. In cases

such as this, we will need to employ the double pour technique. Equipment needed: Suppository mold Pill tile Q-Tips Mineral Oil Glycerin Evaporating dishx2 Hot plate Beaker Water to boil Stirring rod Foil spatula High dose suppository Procedure [Double-Pour]

- *Plan on making slightly extra to compensate for losses during the preparation. So if your Rx calls for 5 or 6 suppositories, lets fill that baby up and make 8. Just be sure to include this in your calculations.

- Weigh your ingredients and label them. Do not leave powders laying around unmarked. o Drug o Base When weighing your base, weigh it in two separate halves. This is for the double-pour.

- Lubricate the suppository mold with the appropriate lubricant. Use Q-tips to spread. Close mold & tighten screws o Fatty blend = Lubricant is Glycerin, because it is opposite polarity o Polybase/PEG = Lubricant is mineral oil, because it is opposite polarity

- On a pill tile, Levigate your drug using the appropriate levigating agent and a spatula o Fatty blend = Levigating agent is mineral oil, because it is the same polarity o Polybase/PEG = Lubricant is glycerin, because it is the same polarity

- Melt half of your base in an evaporating dish on a heated water bath - Add your drug into the melted base. This mixture has ALL of your drug and HALF of your base. Using stirring

rod to disperse drug evenly. - Pour the melted blend into the 8 cavities in the suppository mold. None of the cavities should be completely filled. - Melt the 2nd half of your base on another evaporating dish. Pour the melted base into your first evaporating dish –

this will serve as a rinsing step. - Pour, and overfill the half-filled suppository cavities with your melted base. Allow to cool and harden. - Remove the suppositories from the mold. Clean the mold, and re-lubricate with the appropriate lubricant - Melt the suppositories on a water bath. Using a stirring rod, melt to form a uniform mixture. - Pour the melted drug-base into the mold, fill at least the number of cavities you need to complete the Rx. - Wrap the suppositories in foil. Place them in a box, label, dispense, and counsel.

Quality Control: Uniformity of weight and texture, physical appearance, odor. Review raw materials used for foreign particulates, expiration date, microbial contamination, and general suitability for use.

Low dose suppository Procedure [Single-pour] - *Plan on making slightly extra to compensate for losses during the preparation. So if your Rx calls for 5 or 6

suppositories, lets fill that baby up and make 8. Just be sure to include this in your calculations. o If the amount of required drug is small, it likely has no effect on the suppository volume and may be

disregarded. It may be wise to calibrate your mold to determine the weight of the suppository formed in the mold. So make one. Let it cool. Weigh it. Boom you know.

- Weigh your ingredients and label them. Do not leave powders laying around unmarked. o Drug o Base

- Lubricate the suppository mold with the appropriate lubricant. Use Q-tips to spread. Close mold & tighten screws o Fatty blend = Lubricant is Glycerin, because it is opposite polarity o Polybase/PEG = Lubricant is mineral oil, because it is opposite polarity

- On a pill tile, Levigate your drug using the appropriate levigating agent and a spatula o Fatty blend = Levigating agent is mineral oil, because it is the same polarity o Polybase/PEG = Lubricant is glycerin, because it is the same polarity

- Melt your base in an evaporating dish on a heated water bath o This will require a steam bath if using glycerinated gelatin. See below at end of section.

- Add your drug into the melted base. This mixture has ALL of your drug and ALL of your base. Using stirring rod to disperse drug evenly.

- Pour the melted blend into the suppository mold. - Allow to cool and harden ~15-30 mins. - Remove the suppositories from the mold. Wrap the suppositories in foil. Place them in a box - Label, dispense, and counsel.

Quality Control: Uniformity of weight and texture, physical appearance, odor. Review raw materials used for foreign particulates, expiration date, microbial contamination, and general suitability for use. Counseling: Unwrap before using. Explain the route, it is not for eating. ***Glycerinated-Gelatin as your suppository base! Well you came to the right place

- This one needs to be prepared a little differently. But have no fear, it not that much more difficult - Directions: Heat a water-glycerin mixture to ~80ºC on a steam bath (hotter than water bath)

o Dissolve the gelatin in the water-glycerin mixture. Mix thoroughly with stirring rod Techniques

- Double Pour – for when you are unsure how much space your drug will take up. It’s ok to not know some things. o The formulation is prepared by melting the vehicle, adding drug with mixing to half the vehicle amount o Pour vehicle+drug mixture into the mold cavities. When complete, there should be room in the cavities o Pour Qs our remaining additional suppository base (no drug) to overfill the cavity. Discard excess o Cool the mixture. Now re-melt it (we need the dosage to be uniform, not like candy corn) o Pour, cool, wrap, dispense.

- Suppository Wrapping: Use 3x3 inch foil-square (Images of method featured below) o Place suppository in line with two corners of foil (along a diagonal) o Fold the bottom corner over the middle of the suppository o Fold one corner point over the end of the suppository o Fold the opposite corner point over end of the suppository o Roll the suppository over folded ends into remaining open foil o Dispense in box, remind patient to unwrap suppository before using

(3): TROCHES The objective of troches may be GI, Buccal, Chewable. They may be used for both local and systemic drug administration

Ingredient Function Pharmaceutics Polybase (Perrigo)

Inactive Ingredient. Base. Water-soluble ointment and suppository base. And I guess troche as well! SOFT troches.

Polyethylene Glycol 1450. Aka PEG, or carbowax

Inactive Ingredient. Base. SOFT troches

Glycerinated Gelatin

Inactive Ingredient. Base. Water-insoluble base for multiple dosage form. CHEWABLE gummy troches

Bentonite Inactive. Suspending Agent, increases viscosity

Composition of aluminum oxide, silicon oxide, and other minerals

Sodium Saccharine Inactive. Sweetener Sweetness is 300x sucrose Acacia Inactive. Emulsifying and

Suspending Agent. Increases viscosity

Natural product of calcium, magnesium, and potassium salts of the saccharide arabic acid.

Citric Acid Monohydrate Inactive. Tart flavoring

Kool Aid Inactive. Flavoring Water-soluble. *Be wary of dye content.

Chocolate (Wilton Candy Melts)

Inactive. Flavoring. Chewable Designed for melting in water baths. *Be wary, made in factory with peanuts Used in SOFT troches

Troche Lubricant Inactive. Lubricant Oleaginous Formulations: Use Glycerin Water-miscible formulations: Use light mineral oil or vegetable oil spray

Dosage Form Type

- Hard: Lozenges, Troches, Drops, Lollipop SUGAR BASE o Often contains solid syrups of sugars o Formulation Example: Drug, sugar, corn syrup, water o Purpose: Topical effects or for buccal absorption. Tonsillectomy, mouth ulcers

- Soft: Pastilles WAX, PEG o PEG Formulations, potentially with chocolate o Formulation Example: Drug, PEG 1000, Sweetener o Purpose: Topical effects or for buccal absorption.

- Chewable: Gummies GELATIN o Formulation Example: Drug, Gelatin, Glycerin, Water o Caution – it does not look like medicine o Purpose: Chewed and swallowed for GI absorption

Approach - (1) Determine the appropriate troche type Hard, Soft, Chewable. - (2) Determine the troche base Troche base should represent the objective of the troche - (3) Determine the appropriate lubricant Lubricant must be opposite polarity to the base. - (4) Calibrate your mold and calculations Don’t forget to account for salt-drug versus base-drug weight

Calibrating and Calculating Mold Size

- Gummy Mold (clear plastic trays) o (1) Select desired mold/tray o (2) Fill a small graduated cylinder with water, preferably 10-20mL. o (3) Monitoring your before+after cylinder volume, pour water into the gummy cavities.

§ You can either do 1 cavity, and hope it is an accurate fill and calculation § Or you can try to fill 2 or 3 or 4 cavities with 20mL, divide by the # of cavities, to minimize error. § ***The purpose of this is to determine the drug concentration your troche base will need to be so

that the volume you pour into the mold will provide the desired dose of drug - Troche Mold (white plastic casettes) -- should be ~1gram/cavity

o (1) On an electronic balance, tare a white plastic cassette. o (2) Using a dropper, instill water into a couple wells to capacity. Each well should be empty or full o (3) Reweigh the tray, We know the density of water is about 1g/mL. Depending how many wells you fill,

calculate the average weight of each. Furthermore, you can determine the volume.

Chewable Troche Procedure - This is paraphrased from Dr. Pluta’s caffeine gummy lab protocol- - *Formulation for this experiment: Jell-O, Unflavored gelatin, Glycerin, Purified water - *Mold should be calibrated prior to experiment. See previous page - Weigh/Measure your ingredients and label them. Do not leave powders laying around unmarked.

o Base Gelatin ~will later be hydrated and glycerinated o Drug o Glycerin ~ The volume depends on our Rx and Calibrated mold size o Purified water ~ The volume depends on our Rx and Calibrated mold size

- Add the measured water and glycerin to a large beaker. Heat on hot plate to ~80º F. - Sprinkle gelatin in slowly and evenly. Use a stirring rod to mix and help hydrate the gelatin - Sprinkle Jell-O in slowly and evenly into the large beaker. Mix to form a uniform dispersion. - Allow Jell-O and Knox gelatin to hydrate for approximately 10 minutes, mixing gently. - Heat beaker on hot plate to dissolve gelatin. It should take 10 minutes at 40% heat. Mix occasionally.

o The resulting solution should be clear, and the excessive foam should be removed via spoon - Add drug to the mixture. Stir gently to dissolve. If particles are evident, heat on hot plate as needed. Again –

remove the excessive foam with spoon - Fill the cavities with the drug-gelatin mixture. Either pour directly from the beaker or use a spoon.

o Lubricant? We’ve noticed over time it isn’t needed, but you can if you want. Here – use mineral oil. - Place the gummies in the freezer for 10-15 minutes to solidify. - After gummies solidify, remove the gummies from the mold. Taste and expectorate (QC) - Packaging – either wrap gummies if possible or bag them

Quality Control: Weight, uniformity, appearance, odor, hardness, taste test. Counsel: Chew and swallow, Unwrap before using, Appears as candy, Keep out of reach of children. Watch the BUD. Soft Troche Procedure - Essentially copy-pasted from Pluta’s ‘Compounding Troches’ Non-sterile ppt-

- *Plan on making slightly extra to account for losses. This is shown in the table above. *Calibrate mold. - Weigh/Measure your ingredients and label them. Do not leave powders laying around unmarked.

o Base: Polybase + PEG1450 o Drug Drug A, needing to be dosed at 50mg/troche

- Lubricate the troche mold with the appropriate lubricant o Polybase+PEG1450 are hydrophilic, so we want a hydrophobic lubricant à Mineral Oil

- Prepare a hot water bath to melt base in an evaporating dish. - Cut up base into smaller pieces, and add o the evaporating dish. Stir to facilitate melting with glass stirring rod - On a pill tile, Reduce the particle size of our drug, either by intervention or using a 40-60 mesh screen. Levigate

o Levigating agent in this case will be glycerin - Once base is fully melted, add drug into the evaporating dish and mix until uniform with glass stirring rod

o Putting the drug on the heat source is not standard protocol for all experiments. This depends on the heat sensitivity of the drug. If the drug is heat sensitive, simply remove the dish from heat, cool a bit, add drug

- Pour melted mixture into troche mold, avoid overfilling. Allow to cool. - Once solidified, bend mold to loosen troches. You may tap the mold on the bench to release troches. - Wrap troches individually and dispense in box or vial

Quality Control: Weight, uniformity, appearance, odor, hardness, taste test. Counseling: Unwrap troche before administration. Chew troche to prevent choking. Do not swallow hard or soft troches, allow to dissolve in mouth. Do not use drug once it is past beyond use date. Refrigerate if necessary. Keep away from kids

Ex from class Jell-O: 42g Unflavored gelatin: 7.5g -packet Purified water: 60mL Glycerin: 20mL Glycerin: 20mL

Chocolate Placebo Troche Notes on Compounding - Same as ‘soft’ troche procedure. - Flavor may be added to the chocolate. - It is suggested to instill a few drops of mineral oil to the melted chocolate to facilitate pouring and spreading in

molds. This is a similar concept to lotions being made less viscous by diluting with the levigating agent - When pouring chocolate, pour into the middle of the mold and spread into cavities using a rubber spatula.

Ex: SOFT Troche (Adapted from Pluta’s 25mg Calamine Troches)

Drug K, 25mg Troches #12

- Drug? Calamine. The drug is calamine, it is insoluble. *Will need to levigate - Base: Water-soluble base Ideal base is opposite polarity to drug. - Lubricant: Mineral Oil Lubricant must be opposite polarity of the base. - Procedure:

o Weigh Calamine, label. Weigh Polybase, label. Weigh PEG, label. Label troche mold o Lubricate troche mold with mineral oil. Do not over-lubricate o Levigate Calamine on pill tile with glycerin o Melt polybase and PEG in evaporating dish. Stir continuously, do not let burn. o Disperse calamine in melted PEG-Polybase with mixing. o Fill 12 troche cavities with DrugA-Polybase-PEG mixture. o Do not cover, allow them to harden at room temperature. After cooling, remove troches from mold.

Troches: Quality Control: Weight, uniformity, appearance, odor, hardness Ex: Chewable Troche (Adapted from Pluta’s Glycerinated Gelatin Troches)

Troches #12

- Drug? There is none. - Base: Glycerinated Gelatin Ideal base is opposite polarity to drug. - Lubricant: Mineral Oil Lubricant must be opposite polarity of the base. - Procedure:

o Lubricate Mold with minimal drops of mineral oil, spread with a Q Tip o Weigh bentonite, label. Weigh sodium saccharin, label. Weigh acacia label. Weigh citric acid

monohydrate, lavel. Weigh kool aid flavor, label. o Triturate measured powders together in a mortar and pestle to reduce particle size. o Weigh glycerin into evaporating dish on balance, label. o Add 1.5mL water o Troches: Quality Control: Weight, uniformity, appearance, odor, hardness