Calculations
Sieve Size, Mesh, and Particle Sizes: # 10 sieve has 10 openings per inch in the screen mesh. Particles that can sift through that mesh are said to be
"10 mesh" size.
D.T.D.
"of such dose"
Define Pharmaceutical Compounding
"preparation, mixing, assembling, packaging and labeling of a drug or device in accordance with a licensed practitioner's prescription or medication order under an initiative based on the practitioner/ patient / pharmacist / compounder relationship in the course of professional practice." • Includes non-sterile and sterile preparations
Determination of the Amount of Base Required for making suppositories
(a) weigh the API for the preparation of a single suppository; (b) Transfer the API into a suppository mold cavity (c) add melted base to the cavity to fill it completely (d) allow the suppository to congeal and harden; and (e) remove the suppository from the mold and weigh it. The weight of the active ingredients subtracted from the weight of the suppository yields the weight of the base. This amount of base multiplied by the number of suppositories to be prepared in the mold is the total amount of base required.
Preparation of suppositories: 3. Compression method:
- A uniform drug and base mixture is produced by hand rolling method. The mixture is placed into suppository compression device. Pressure is applied and the mixture is forced into lubricated compression mold cavities. The mold is then cooled and the suppositories are ejected. - Compression is especially suited for making suppositories that contain heat-labile medicinal substances or a great deal of substances that are insoluble in the base. - In contrast to the molding method, compression permits no likelihood of insoluble matter settling during manufacture. - The disadvantage to compression is that the special suppository machine is required and there is some limitation as to shapes of suppositories that can be made. - For heat stable drugs, the base is molten on a water bath and the drug powder is dispersed uniformly. The mixture is cooled to get a dry powder mass. The powder is passed through a required sieve to get uniform granules. The granules are compressed to get the suppositories.
Gels Method of Preparation: Medicated gels
- API may be dissolved before or after gel has been formed depends on its interference with the gel formation. - Basic drugs can be dissolved in an organic solvent such as alcohol and added to Carbomer solutions, to form spontaneous gels.
Disadvantages of Rectal Route
- Absorption may be interrupted by defecation. - has a small surface area for passive absorption. - A small rectal fluid content may cause problems with drug dissolution or absorption. - Patients generally do not prefer suppositories because of their inconvenience. - Rectal absorption of most drugs frequently is erratic and unpredictable - Vaginal suppositories may "leak" or are expelled after insertion depending on their size and shape.
Colloids Examples
- AquaMEPHYTON injection is a colloidal solution of vitamin K1. - injection by intravenous, intramuscular, and subcutaneous routes - Inactive ingredients: Polyoxyethylated fatty acid derivative 70 mg; Dextrose 37.5 mg; Water for Injection, q.s. 1 mL and Benzyl alcohol 0.9% added as preservative. - Colloidal COPPER and PLATINUM are used in cancer chemotherapy, and colloidal GOLD is a diagnostic agent.
BUD
- Beyond Use Date - The date after which the compounded preparation should not be used
Manual Methods of Comminution (compounding): Pulverization by intervention
- Comminution by utilizing a SOLVENT that can be easily removed. - e.g. Ethanol and Menthol
Drug Release from Suppositories: Water soluble (PEG)
- Dissolve upon insertion to release their API - Dissolution is slow (few hours) due to the small volume of rectal fluid available - mixes with the rectal fluid and releases API directly into the fluid - water soluble suppository bases release polar and non-polar drugs equally well - Water soluble suppository bases are probably a better choice for very lipid soluble drugs for example, Diazepam
Ointment bases: 4. Water Soluble Bases Advantages
- Easily removed off from skin by washing with water - leave no oil residue on skin - can absorb some water or alcohol; therefore, permit inclusion of a small amount of aqueous or alcoholic solutions. - contain no water and are suitable for incorporation of solid drug powders that are sensitive to hydrolysis (e.g., Erythromycin)
Suppository Bases: 1. Fatty or oleaginous bases: Examples
- Fattibase - Wecobee base - Witepsol base - Cocoa butter: naturally occurring - Fatty bases melt at body temperature and drug has to partition from base to rectal membrane for absorption - Refrigeration is needed for all suppositories made with fatty or oleaginous bases because they melt at ambient temperatures, hand touch, etc.
2. Bulk Powders Dusting Powders:
- Fine powder dusted on the skin by means of sifter top containers - Powder base vehicles will absorb secretions and dry the area and impart a cooling effect - Small Particle size to be grit-free and avoid irritation
Preparation (compounding) of ointments 2. Fusion method (melting)
- Fusion used to compound ointments when incorporation cannot be used, e.g., spatulation can not be used to incorporate white wax or any other stiffening agent into petrolatum. - fusion is most commonly used to prepare ointment bases and is not commonly used to add a drug to an ointment bas • water bath is used to melt/dissolve components of ointment base - melt is blended by stirring then active ingredient, if any, is added as a solution, and stirring is continued during cooling to prevent component separation - heat-labile substances and any volatile components are added last, when temperature of mixture is low enough not to cause decomposition or volatilization of components - Substances may be added to congealing mixture as solutions or as insoluble powders levigated with a portion of the base
Source of Active Ingredient for Compounding:
- Obtaining pure powder form of API for average retail or hospital pharmacy is difficult, time consuming and expensive - Best source of API is a commercially prepared product: tablets and capsules - Tablets may be comminuted and capsule contents emptied for use in compounding pharmacy
Preparation (compounding) of ointments 1. Incorporation method (mechanical blending)
- Ointment base + API mixing in a glass mortar and pestle - When possible, solid drug(s) added to ointment base as a solution to ensure a uniform blend and to eliminate grittiness - When not possible, powder(s) should be levigated to minimize grittiness and increase effectiveness (due to a decrease in particle size). - Levigation removes adsorbed air on particles, make them easily wettable. - levigating agent (e.g., mineral oil, glycerol) should be equal in volume to solid material - ointment is prepared by thoroughly rubbing and working components together on hard surface (slab) until product is smooth and uniform - Levigation will decrease particle size, removes adsorbed air on particles; this step would no way affect viscosity of final product. - After levigation, dispersion is incorporated into ointment base by spatulation or with mortar and pestle until product is uniform. Triple roller mill (mini-size) can also be used. - For incorporating a gummy material, such as camphor, pulverization by intervention can be used; material is dissolved in a solvent and spread out on ointment slab or pill tile - solvent is allowed to evaporate, leaving a thin film of material onto which other ingredient or ingredients are spread
Describe properties specific to a paste in comparison to other semi-solids
- Ointment or a gel base + high % insoluble particulate solids (>20%) so are STIFFER - less greasy (not really) and more absorptive than ointments - better at absorbing skin secretions, and less penetrating and stay in place on skin than ointments - good protective barriers when placed on skin - form an unbroken, water-impermeable film on skin surface and are protectants; unlike ointments, film is opaque and an effective sun block - not suitable for hairy parts of body
What is powder?
- Oldest dosage form - Oral powders have been replaced by tablets and capsules - Compounding powders is not unusual for geriatric and pediatric patients!
Suppository Bases: 2. Water Soluble Bases:
- PEGs are commonly used for rectal suppositories - MW of PEGs range from 200 to 8000. MW 200 to 600 are clear liquids, MW >1000 are wax like white solids. Solid and liquid PEGs can be blended to obtain semi-solids (ointments) and solids (suppositories) of desired consistency - Do not melt but dissolve slowly in body fluids and release drug for absorption. Water soluble drugs (e.g., salt form of an insoluble drug) are readily available for absorption. Water insoluble drugs are incorporated in the suppository as fine particles for better dissolution. - They are somewhat hygroscopic - Refrigeration is NOT needed for suppositories made with PEG bases
Colloids
- Particle size range: 0.1 to 0.5 μm (1 nm to 500 nm)!! - E.g., inorganic colloids, association colloids, microemulsions, nanoparticles - Colloidal particles are larger than atoms, ions, or molecules, and consist of a single, large molecule of high molecular weight or aggregates of smaller molecules
Small-Scale Blending Equipment
- Pill tile and spatula - Mortar and pestle - Bottle/container - Plastic baggie
Ointment bases: 4. Water Soluble Bases Examples
- Polyethylene Glycol Ointment, - NF (Polyethylene glycol 3350, 40%, - Polyethylene glycol 400,60%): This ointment is prepared by melting PEG 3350 at 70oC, and adding PEG 400 and mixing well. This results in a very pliable semisolid ointment.
Ointment bases: 1. Hydrocarbon bases (oleaginous bases) Disadvantages
- Poor patient acceptance because of greasy nature - Are not removed easily with washing - Cannot absorb water, so most liquid ingredients are difficult to incorporate into hydrocarbon bases, and aqueous skin secretions do not readily dissipate across the base.
Gels Method of Preparation: Cold water method
- Some gelling agents are more soluble in cold water than in hot water. - e.g., methylcellulose and poloxamers
Gels Method of Preparation: Hot water method
- Some gelling agents gel only in hot water than in cold water. - e.g., starch and gelatin
Define Pastes
- Stiff, semisolid dosage forms that contain one or more drug substances intended for topical application. - contain more solid material than ointments, generally at least 20% of solids; e.g., Zinc Oxide Paste
Powdered dosage form storage and stability
- Store in dry places. - Protect from light in some cases. - Keep out of reach of children. - Expiration date is a manufacturer defined term based on very specific testing used for commercially available products.
Gelling agents Examples
- Synthetic: Carbomers, Poloxamers, Polyvinyl alcohol - Semisynthetic: Hydroxypropyl Methyl cellulose, carboxymethyl cellulose sodium - Natural: Xanthan gum, Gellan gum, Tragacanth
Granule Preparation: Fusion or dry method (Compounding of effervescent granules )
- The blended powder is heated in a beaker on a water bath while stirring. - The heat releases the citric acid water of hydration (monohydrate) to the other powders causing them to become sticky. - The wet mass is forced through a sieve [# 8] to make granules, which are then allowed to dry before packaging
2. Bulk Powders Powder Insufflations:
- These are finely divided powders introduced (blown) into body cavities - When the rubber bulb is depressed, internal turbulence blow the powder through orifice into nose, throat, tooth socket, or skins
Ointment bases: 3. Water-Removable Bases
- These are oil-in-water emulsions bases; also called as creams - Because external phase of emulsion is aqueous, they are easily washed from skin, hence are called as water-removable bases or water-washable bases.
Categories of Powders as a Dosage Form: 2. Bulk Powders
- These are powders dispensed in a bulk container containing multiple doses. - Oral bulk powders - Dentifrice powders - Douche powders - Dusting Powders - Powder Insufflations
Categories of Powders as a Dosage Form: 1. Divided Powders
- These are powders dispensed in the form of individual doses - Oral divided powders and powders for inhalation
Ointment bases: 2. Absorption bases b. w/o emulsion absorption bases
- Those that are w/o emulsions that permit the incorporation of additional quantities of aqueous solutions - e.g., Lanolin, Hydrocream®, Eucerin®
Ointment bases: 2. Absorption bases a. Anhydrous absorption bases (emulsifiable bases)
- Those that permit the incorporation of aqueous solutions resulting in the formation of w/o emulsions - eg: Anhydrous Lanolin, Hydrophilic Petrolatum, Aquaphor®
Packaging of semisolid preparations
- Topical dermatologic products are packaged in either jars or tubes, whereas ophthalmic, nasal, vaginal, and rectal semisolid products are almost always packaged in tubes. - Tubes are light in weight, relatively inexpensive, convenient for use, and compatible with most formulative components, and they provide greater protection against external contamination and environmental conditions than jars. - Ointment tubes are made of aluminum or plastic. When the ointment is to be used for ophthalmic, rectal, vaginal, aural, or nasal application, they are packaged with special applicator tips. - Ointment jars are filled on a small scale in the pharmacy by carefully transferring the weighed amount of ointment into the jar with a spatula. - Ointments prepared by fusion may be poured directly into the ointment jar to congeal in it.
Manual Methods of Comminution (compounding): Levigation
- Triturating while moistened with a liquid in which the powder is INSOLUBLE. - e.g. mineral oil or glycerin
Ointment bases: 2. Absorption bases Advantages
- Very good emollient, protective and occlusive properties - Do not wash off easily from skin, hold medications. - Absorb and retain liquids - Some lanolin-types have compositions have similar skin compositions (they are obtained as sebaceous secretions of the skin)
Ex: Formulation 4 Atropine Sulfate 0.6 mg Lactose qs 300 mg M. Ft. D.T.D. Divided Powders # 9 The available source of API (AS) are tablets which contain 1.2 mg Atropine Sulfate in each tablet. Also each tablet weighs 100 mg, including inactive ingredients. To compensate for powder loss due to handling, prepare one extra dose. Please calculate the number of tablets and amount of lactose needed to compound this preparation.
- We need to prepare 9+1 doses. - Total weights of Atropine sulfate: 0.6 mg x 10 = 6 mg - The number of tablets needed: 6 /1.2 = 5 (tablets) - Total weights of tablets (including inactive ingredients): 100 x 5 = 500 mg - Total weight of powders: 300 mg x 10 = 3000 mg - The amount of Lactose needed: total weight of powders (3000 mg)- total weight of tablets (500 mg) = 2500 mg
Ointment bases: 2. Absorption bases
- can absorb water and form w/o emulsions (creams) - two types anhydrous and w/o emulsion - Anhydrous absorption bases + water = w/o emulsion absorption bases - Not easily removed from skin with water washing, since external phase of emulsion is oleaginous - Water or hydro-alcoholic soluble drugs can be dissolved and incorporated into absorption bases
Ointment bases: 4. Water Soluble Bases Disadvantages
- cause irritation on denuded or abraded skin or mucous membranes. - have no emollient properties - liquefy with addition of water - May promote oxidation of incorporated drugs - Chemical stability problems due to water - If the ointment formula has water, microbial growth occurs, hence needs addition of a preservative.
Inserts
- compressed tablets used as vaginal suppositories - normally supplied with an inserting device for placement of tablet high in vaginal tract
Manual Methods of Comminution (compounding): Trituration
- continuous rubbing or grinding of powder with mortar and pestle (reduce size and mix) - Suitable for hard and fracturable powders - Tools: Pill tile and spatula or Mortar and pestle
Gels Method of Preparation: 1. Non-solvent dispersion method
- disperse powder with a water miscible nonsolvent such as alcohol, glycerin, or propylene glycol; then dilute with water. - E.g., sodium carboxymethylcellulose. Otherwise lumping will occur.
Suppositories for Local Action Rectal Suppositories
- intended for local action are most frequently used to relieve constipation, pain or irritation , itching, and inflammation associated with hemorrhoids or other ano-rectal conditions. - Glycerin suppositories promote laxation by local irritation of mucous membrane probably by dehydrating effect of glycerin
1. Divided Powders Powders for Inhalation
- intended to be inhaled deep into the lungs with the use of special metered dose inhalers - powders dispensed under pressure
Ointment bases: 3. Water-Removable Bases Disadvantages
- less protective, less emollient, and less occlusive - have incompatibilities with ionic agents due to the use of soap-type emulsifying agent in the cream formula - Chemical stability problems for drugs due to presence of water - require use of an antimicrobial preservative because of presence of water - may "dry out" due to evaporation of water. Hence humectants such as glycerol or propylene glycol are required
Colloid Properties
- more than one shape (globules, rods, flakes, threads, and branched rods) - Association colloids are dispersions of micelles - Brownian movement: particles diffuse very slowly due to Brownian motion and this diffusion offsets effect of gravity so particles never settle to the bottom of their container. - exhibit colligative properties - particles will never settle or sediment to the bottom of the container unlike coarse dispersions (suspensions and emulsions)
Drug Release from Suppositories
- must be released and dissolve in small amount of aqueous rectal fluid to be absorbed - if API is particle in suppository a decrease in particle size results in faster dissolution and absorption
The rectal route of administration is viable when
- nausea and vomiting and swallowing difficulties - unconscious - infants/small children - severely debilitated conditions - hospice patients
Suppository Bases - Ideal Properties
- nontoxic, nonirritating, inert, compatible with drugs and other ingredients, and easily formed by compression or molding - base should also dissolve and release drug in the local fluids or melt at body temperature to allow for the release of medication - suppository base composition plays an important role in both the rate and extent of release of medications
Suppositories for Systemic Action Urethral Suppositories
- one example; MUSE® (alprostadil) - single-use medicated transurethral system for the treatment of erectile dysfunction.
Packages of Powders
- powder blower or insufflator - wide mouth screw-cap glass jars - cardboard bulk powder boxes (oral bulk powders) - sifter-top cans (dusting powders)
Drug Release from Suppositories: Fatty (oleaginous, e.g., cocoa butter) suppository bases
- quickly melt (10 min) to form oily pool - immiscible with rectal fluid - slow an incomplete absorption of lipid soluble drugs which have difficult time partitioning from oil which they are dissolved (wants to remain in oily pool) - fatty suppository bases are probably a better choice for water soluble drugs because oily soluble drugs don't absorb easy
Rectal absorption
- rectum has very abundant blood supply and lymphatic vessels for drug absorption - inferior and middle hemorrhoidal veins surround rectum drain directly into inferior vena cava - Drugs absorbed by these veins avoid first pass effect. - upper (superior) hemorrhoidal veins drain into portal circulation and drugs absorbed by this vein are subjected to first pass effect so drugs should not be placed too deep into rectum - must be released from suppository and dissolve in small amount of aqueous rectal fluid to be absorbed - if API exists as particles in suppository, a decrease in particle size normally results in faster dissolution and absorption
Define Creams
- semisolid emulsions dosage forms containing one or more drug substances dissolved or dispersed in a suitable base - formulated as either water-in-oil (e.g., Cold Cream) or oil-in-water (e.g., Fluocinolone Acetonide Cream) emulsions
Creams
- semisolid preparations containing one or more medicinal agents dissolved or dispersed in a o/w emulsion. - Recently USP restricts definition of cream to o/w emulsions only. - semi-solid o/w emulsions containing large percentages of water and stearic acid or other oleaginous components. - After application, water evaporates, leaving behind a thin residue film of stearic acid or other oleaginous components - Creams have a creamy or shiny appearance as result of refraction/reflection of light from their emulsified phases. - Many patients and physicians prefer creams to other ointments because they are easier to spread and remove from skin. - Pharmaceutical manufacturers frequently manufacture topical preparations of a drug in creams over other ointment bases to satisfy preference of patient and physician
Define Gels
- semisolid systems consisting organic elongaged macromolecules in an aqueous or non-aqueous liquid, interlaced and interpenetrated by a liquid with no definite boundary between the solid and liquid phases. • organic macromolecule is called as a gelling agent - gels formulated to contain a drug substance, solvents, antimicrobial preservatives, antioxidants and chelating agents
Packages of Divided Powders: Plastic Packets
- small sealable (zip lock) plastic bags (tiny sandwich bags) the easiest package to use and offer much greater protection from the atmosphere - loss of the powder to the packet is a concern
Suppositories
- solid dosage forms intended for insertion into body orifices where they melt or dissolve and exert localized or systemic effects.
Gels Method of Preparation: Neutralization method
- some gelling agents are acidic in nature, readily dissolved in tepid water to form a solution. These require an alkali to neutralize to produce sparkling clear gels. - E.g., Carbomers
The preferred ointment base for formulating a diaper rash preparation is A. Oleaginous bases B. W/O emulsion (Absorption bases) C. O/W emulsion (water removable bases) D. Water soluble bases Because of the reason(s) A. non-greasy B. Washable C. Protectant D. emollient
1. A. Oleaginous bases 2. C. Protectant D. emollient
Ex Question #2 1. You have levigated #12 methyldopa 250 mg in 5-10 mL of simple syrup then QSAD to 120 mL. What is the total daily dose in teaspoons for someone needing 250 mg PO Q8H? 2. How would you write out the label directions for this patient?
1. 12 tabs x 250 mg/tab = 300 mg 300 mg/120 mL = 25 mg/mL 250 mg/dose x 3 doses/day x 1 mL/25 mg x 5 mL/1 tsp = 6 tsp/day 2. take 10 mL by mouth every 8 hours
Ex: You are making a naratriptan suspension using #24 naratriptan 2.5 mg tablets. The final concentration needs to be 0.5 mg/ml. 1. How many ml will the final preparation need to be?
1. 120 mL
Ex: Prescription 3: Drug: Cefdinir 125mg/5mL Sig: 7 mg/kg BID x 5 days Quantity: QS Refills: 0 Patient weight: 42 lbs Questions: 1. How many mg/kg will the patient take per day? 2. How many mg/kg will the patient take per dose? 3. How many mL will the dose be? 4. What total volume would you need to dispense?
1. 14 g/kg per day 2. 7 mg/kg per dose 3. 5.3 mL 42/2.2 = 19; 19 x 7 mg/kg = 133 mg; 133 mgx5 mL/125mg = 5.3 mL 4. 5.3 mL x 2 x 5 = 53 mL may come in 60 mL bottle then waste 7 mL
Ex: Prescription 4: Drug: Cefdinir 125mg/5mL Sig: 14 mg/kg per day in 2 divided doses x 10 days Quantity: QS Refills: 0 Patient weight: 53 lbs Questions: 1. How many mg/kg will the patient take per day? 2. How many mg/kg will the patient take per dose? 3. What total volume would you need to dispense?
1. 14 mg/kg 2. 7 mg/kg 3. 134.3 mL
Ex: Prescription 6: Acetaminophen 325 mg Alcohol USP 15 ml Cherry Syrup qs 90 ml Dispense: 180 ml Refills: 1 SIG: Take 1 tbsp PO Q4-6H PRN fever Questions: 1. What will be the total volume dispensed? 2. How much cherry syrup will be used to prepare this order? 3. How much acetaminophen will be used to prepare this order? 4. What would have been a better way to write the sig?
1. 180 mL 2. 150 mL 3. 650 mg 4. take 15 mL PO
You need to make 134 ml of a captopril 0.75 mg/ml suspension. 1. How many captopril 50 mg tablets (number of tablets) are needed to crush and add to the 50/50 combination of Ora-Plus and Ora-Sweet?
1. 2 tablets
****Question #5 1. You have commercially available carbamazepine syrup on the shelf (40 mg/mL). You need to dilute it for an infant to 20 mg/mL. Using a graduated cylinder, you measure your quantity on hand and find you have 236 mL in your stock bottle. How much Simple Syrup NF (in mL) needs to be added to achieve the desired concentration? 2. What if you needed to dilute the carbamazepine syrup (40 mg/mL) to 15 mg/mL? How much Simple Syrup NF (in mL) needs to be added to the 236 mL you have on hand?
1. 472 mL (total) - 236 mL (carb) = 236 mL Simple syrup 2. 393 mL
****Ex Prescription: Midazolam 5 mg/ml injection 10 ml Watermelon flavored gelatin 0.5 ounces Purified Water USP QSAD 20 ml Div. in container #4 SIG: 1 container PO before each MRI Refills: 0 Questions: 1. What will be the volume of each dose (container)? 2. What will the final concentration (mg/mL) of midazolam in this preparation? 3. How much midazolam (in mg) will be given in each dose?
1. 5 mL 2. 2.5 mg/mL 3. 12.5 mg
Ex: You compound a prescription using the following monograph: Sumatriptan 100 mg tablets #6 Ora-Plus 30 ml Ora-Sweet QSAD 120 ml 1. What is the final concentration of this compound (in mg/ml)? 2. How much Ora-Sweet will you use?
1. 5 mg/mL 2. 90 mL
Selection of the Appropriate Base
1. Desired release rate of the drug substance from the ointment base 2. Desirability of topical or percutaneous drug absorption 3. Desirability of occlusion of moisture from the skin 4. Stability of the drug in the ointment base 5. Effect of the drug on the consistency of the ointment base 6. Desire for a base that is easily removed by washing with water 7. Characteristics of the surface to which it is applied
Ex: Prescription 5: Acetaminophen 975 mg Alcohol USP 30 ml Cherry Syrup qs 120 ml Dispense: 120 ml Refills: 1 SIG: Take 5 mL PO Q4-6H PRN fever Patient Weight= 7.9 pounds Questions: 1. How do you know this is an order to be compounded? 2. What does "QS" mean? 3. What will the total volume of this preparation be? 4. How much cherry syrup will be used?
1. Different amounts of different ingredients; tells us to QS this 2. Quantity sufficient 3. 120 mL 4. 90 mL
1. A teenage girl was given a prescription for 2% erythromycin for the topical treatment of acne vulgaris. Erythromycin is a lipophilic drug, unstable in the presence of moisture. The topical preparation is required a rapid and predictable release of drug from the base. Select an appropriate ointment base for this formulation. A. Oleaginous base B. Anhydrous absorption base C. w/o emulsion base D. o/w emulsion base E. Water soluble base
1. E. Water soluble base
Advantages of Powders
1. Easy to swallow 2. Relative stability (more stable than liquid) 3. Rapid onset of action 4. Large doses possible 5. Avoid irritation caused by very soluble salt tablet
Steps in the Compounding Process
1. Evaluate the order/situation to determine if the product should be compounded 2. Perform necessarily calculations to determine amount of all necessary ingredients 3. Determine most accurate method of measurement for all ingredients 4. Identify and prepare the equipment 5. Obtain appropriate personal protective gear 6. Prepare the compounding space 7. Assemble all active ingredients, excipients, supplies, and any other materials 8. Compound the pharmaceutical formulation according to the medication order or monograph 9. Ensure the compounded preparation meets standards of consistency, blending, color, clarity, odor, pH, and other visual or scientific testing as appropriate 10. Document in the compounding log as required by law 11. Package and label the compounded preparation 12. Sign and date the prescription, affirming that all procedures were carried out to ensure uniformity, identity, strength, quantity, and purity 13. Clean all equipment thoroughly and promptly and store properly 14. Counsel patient
5 Advantages of granules over powders
1. Granules flow better because of smaller surface area 2. Granulation prevents un-mixing (stratification) of powder blends 3. Dust problems associated with the handling and processing of fine powders are minimized by granulation 4. granules are more stable to atmospheric water and oxygen (Since granules have a smaller surface area than powders ) 5. Granules are more easily wetted by water
Ointment bases are classified by the USP into four general groups:
1. Hydrocarbon bases 2. Absorption bases 3. Water removable bases 4. Water soluble bases
Ointment bases: 3. Water-Removable Bases Examples
1. Hydrophilic Ointment USP (Methylparaben 0.025%, Propylparaben 0.015%, Sodium Lauryl sulfate 1%, Propylene glycol 12%, Stearyl alcohol 25%, White petrolatum 25%, Purified water 37%) 2. Vanishing Cream (Stearic acid 25%, triethanolamine 2%, glycerin 12%, purified water 61%)
Ointment bases: 2. Absorption bases Examples
1. Hydrophilic Petrolatum USP (Cholesterol 3%, Stearyl alcohol 3%, White wax 8%, White petrolatum 86%) 2. Lanolin, USP obtained from the wool of sheep, contain wool fats and alcohols with emulsifiable properties. 3. Cold Cream: (White Wax 12%, Cetyl Esters Wax 12.5%, Mineral Oil 56%, Sodium Borate 0.5%, Purified Water 19%)
Preparation of suppositories: Fusion method - general procedure:
1. Melt the base (PEG or cocoa butter) 2. Disperse the finely divided drug powder uniformly in the melted base by continuous stirring 3. Pour the mixture into the mold continuously to avoid layering. 4. After the suppositories congeal they may be placed in refrigerator to harden. 5. Trim the surface with a spatula and open the mold and collect the suppositories and pack them.
Label Requirements
1. Name of the preparation 2. Strength of the preparation 3. Internal lot number or identification number of the compounded preparation 4. Do not use beyond date 5. Storage instructions (room temperature, refrigerator, freezer, light protected, etc.) 6. Initials of the pharmacist who compounded or verified the prescription 7. Any other statements required by law
Disadvantages of Powders
1. Not suitable for drugs with unpleasant taste/odor 2. Less stable than tablet or capsules because of large surface area 3. Relative expensive than tablet or capsules
4 Importances of Particle Size
1. Particle size affects rate of drug dissolution and bioavailability 2. Ensure content from dose to dose (separation of particles of significantly different sizes) 3. Penetrability of particles to be inhaled for deposition in respiratory track 4. Non-grittiness of solid particles in dermal ointments, creams and ophthalmic preparation (fine powder)
Ointment bases: 1. Hydrocarbon bases (oleaginous bases) Examples
1. Petrolatum USP: purified mixture of semisolid hydrocarbons obtained from petroleum; greasy substance, melts at 38° to 60°C and may be used alone or in combination with other agents (such as wax or mineral oil) as an ointment base. 2. Yellow Ointment USP (Yellow wax 5% + Petrolatum 95%); has a slightly greater viscosity than plain petrolatum. 3. White Ointment USP (white wax 5% + Petrolatum 95%); White wax is a purified form of yellow wax and white petrolatum is a purified form of petrolatum
Types of suppositories
1. Rectal: cylindrical, bullet or torpedo shaped and may weigh about 2 g 2. Vaginal: called pessaries, are usually globular, oviform, or cone-shaped and weigh about 5g 3. Urethral: called bougies (boo-zhees), are slender and tapered (pencil-shaped), suppositories often about 5 mm in diameter and up to about 60 mm long
Particle Size and Surface Area: A powder consists of cubes of 2mm on edge, and it is reduced to particle 1 mm on edge. 1. What is the change of particle number? 2. What is the change of surface area? 3. What is the effect on drug dissolution?
1. Reduce particle size 2mm -> 1mm 1. Increase particle number 1 cube -> 8 cubes 2. Increase surface area 24 mm2 -> 48 mm2 3. Increase dissolution rate Noyes-Whitney Equation
Blending Powders Steps in Forming
1. Reduce particle size until uniform with other ingredients. 2. Start with substance present in the smallest amount and add ingredient with next larger quantity (if practical) using geometric dilution technique. 3. Continue adding substances until all are added and uniformly mixed.
Powder Compounding Steps
1. Reduction of particle size of all ingredients. 2. Sieving 3. Weighing of each ingredient. 4. Mixing 5. Weighing individual doses (divided powders only) 6. Packaging and Labeling
Gels Routes of Administration
1. Skin and Scalp: NSAIDs treat inflammations of skin and scalp because creams and ointments are too greasy 2. Eye: anti-glaucoma agents 3. Nose: Testosterone nasal gel for treatment of male hypogonadism 4. Vagina: (lubricants) 5. Rectum (ex: diazepam)
Ex: Prescription 1: Drug: Cefdinir 125mg/5mL Sig: Take 10mL po BID x 5 days Quantity: QS Refills: 0 Questions: 1. What dosage form is this product? 2. Why is this considered a compounded prescription? 3. What does "QS" mean? 4. What total volume would you need to dispense?
1. Suspension 2. Needs to be reconstituted 3. Quantity sufficient (for the 5 day duration) 4. 100 mL = 10 mL x 2 twice daily x 5 days
Differences in "Expiration Dates" - 3 types of expiration dates to consider when compounding
1. The expiration date for the medication order or prescription 2. The expiration date of each ingredient used to compound the preparation 3. The expiration date of the compounded preparation
Ointments, Creams and Pastes: 1. They may be applied to 2. They may be 3. The unmedicated ones are used for
1. They may be applied to -The skin, Surface of the eye, Used nasally, vaginally, or rectally. 2. They may be medicated or unmedicated 3. The unmedicated ones are used for their physical effects as protectants, emollients or lubricants.
Which bases contain water?
1. Water removable bases 2. Absorption bases (water/oil emulsion bases) -bases with water are unstable
Granule Preparation: Wet Granulation
1. Wet the powder with a liquid ( water or ethanol) to form a paste. 2. Formation of granules starting from the paste, using granulator or pass through a screen. 3. Dry in oven 4. The Classification of the granules with sieve
Packages of Divided Powders: Folded powder papers (the more traditional method)
1. White bond: opaque and neat appearance but NOT moisture resistant 2. Vegetable parchment: semi-opaque and moisture resistant 3. Glassine: newest and most commonly used weighing paper; glazed, transparent, and moisture resistant 4. Waxed: transparent, but waterproof.
Ex: Prescription 2: Drug: Cefdinir 125mg/5mL Sig: Take 2 tsp po BID x 5 days Quantity: QS Refills: 0 Questions: 1. What if the sig had been written for "tsp" rather than "mL"; How would that change the total volume to be dispensed? 2. How many mg per dose will the patient be taking? 3. What is the total daily dose of cefdinir (in mg) that the patient will be taking?
1. Wouldn't change because 1 tsp is 5 mL and 2 is 10 mL 2. 250 mg = 10 mL x 125 mg/ 5 mL 3. 250 mg x 2 times daily = 500 mg
How to Fold Powder Papers
1. place paper on counter away from wind 2. fold down top long edge of paper 1/2 inch 3. place weighted dose of drug in center of paper 4. bring lower edge of paper up and insert it into the top fold of powder paper and make a second fold in the top edge of the paper 5. center folded paper lengthwise over an open powder box then fold the equal overhanging ends down while pressing in the sides of the box 6. fold ends of powder paper back and crease the end folds then place the filled powder paper into the box with fold away from you 7. prepare a folded paper for each dose
Question #3 You are making a metolazone suspension using #12 metolazone 10 mg tablets. The final concentration needs to be 3 mg/mL. What volume is the final product?
12 tabs x 10 mg/tab x 1 mL/3mg = 40 mL
Ex Question #1 You need to make 120 mL of a metronidazole 50 mg/mL suspension. How many metronidazole 250 mg tablets are needed to crush and add to the 50/50 combination of Ora-Plus and Ora-Sweet to compound this prescription?
120 mL x 50 mg/mL = 6000/250 mg = 24 tablets
Ex: Effervescent Granules Rx Active drug 500 mg / 5g tsp in effervescent granule qs 120 g Sig: Dissolve in 1 teaspoonful in one-half glass of cool water and drink. Repeat this every 8 h. Effervescent vehicle needed?
120/5= 24 dose 24*0.5g= 12 g active drug 120- 12 =108 g effervescent vehicle
What BUD would you assign for an aqueous oral solution?
14 days when stored at a controlled cold temperature
1 Tbsp = ? mL
15 mL
1 oz = ? Tbsp
2 tbsp
Question #4 •HG is an 11 year-old male weighing 95 lbs. He needs 50 mg/kg/day (2 gram maximum) of tinidazole suspension. You need the dose volume to not exceed 15 mL (1 tablespoon) and you need a 5 day supply. How many tablets do you need to make the suspension if you have tinidazole 500 mg tablets on hand?
20 tablets
1 Tbsp = ? Tsp
3 tsp
1 oz = ? mL
30 mL
1 Tsp = ? mL
5 mL
Ex: Prescription 6: Acetaminophen 325 mg Alcohol USP 15 ml Cherry Syrup qs 90 ml Dispense: 180 ml Refills: 1 SIG: Take 1 tbsp PO Q4-6H PRN fever Questions: 5. What will the final concentration (mg/mL) of this preparation be? 6. How much acetaminophen per dose will the patient receive? 7. What will be the days supply if the patient takes the maximum allowed dose?
5. 3.6 mg/mL 6. 54.2 mg 7. 2 days
Ex: Prescription 5: Acetaminophen 975 mg Alcohol USP 30 ml Cherry Syrup qs 120 ml Dispense: 120 ml Refills: 1 SIG: Take 5 mL PO Q4-6H PRN fever Patient Weight= 7.9 pounds Questions: 5. What will the final concentration (mg/mL) of this preparation be for acetaminophen? 6. How much acetaminophen per dose (in mg/kg) will the patient receive? 7. How much acetaminophen will the patient receive per day if they take the maximum allowed dose?
5. 8 mg/mL = 975/120 6. 40.6 mg; 7.9/2.2 = 3.6 kg 40.6/3.6 kg = 11.1 mg/kg per dose 7. 6 times in 1 day at 40 mg = 240 mg
1 cup = ? oz
8 oz
Preparation of suppositories: 1. Hand-rolling method:
A finely powdered drug is mixed with grated base in a motor and pestle using levigation and geometric dilution techniques. A small amount of fixed oil may be added to facilitate the preparation. The mass is hand rolled into suppositories.
Ex: Formulation 5 Rx Acetaminophen 1200 mg Codeine phosphate 300 mg Lactose q.s. 6000 mgM. et ft. capsules No. XX Sig: i q6h prn pain
A mixture should be prepared of the ingredients in the amounts listed and then divided into the number of dosage forms indicated. In this case, the ingredients would be divided into 20 capsules, each containing 60 mg acetaminophen, 15 mg codeine phosphate and enough lactose to make a total of 300 mg
Geometric Dilution
A process that thoroughly mixes a small amount of a drug with an appropriate amount of a diluent.
Humectant
A substance that causes water to be retained because of its hygroscopic properties
Occlusive
A substance that promotes retention of water in the skin by forming a hydrophobic barrier that prevents moisture in the skin from evaporating
Protective
A substance that protects injured or exposed skin surfaces from harmful or annoying stimuli
Emolient
An agent that softens the skin or soothes irritation in skin or mucous membrane
A physician requests that you formulate an antibiotic cream that provides a moderate and continuous release of medication. The physician also requests that the formulation be easy to apply and remove because the area is severely irritated. The antibiotic is a hydrophilic substance and is stable in the presence of moisture. Which ointment base type would you recommend? A. Oleaginous base B. w/o emulsion base C. o/w emulsion base D. Water soluble base
C. o/w emulsion base
Examples PEGs in Suppository Base Compositions:
Can use various solid and liquid proportions to make a suppository
Which type of ointment base would be appropriate to meet the following criteria for a given drug? • Very lipophilic drug • Drug is hydrolyzed in aqueous solution • Desire a rapid and predictable release A. Oleaginous B. Absorption (w/o emulsion) C. Water removable/washable (o/w emulsion) D. Water soluble
D. Water soluble
Powders versus Granules: Powders
Dosage forms that consist of particles of size about 0.1 to 10 mm
Powders versus Granules: Granules
Dosage forms that consist of particles of size about 0.5-10 mm
Inserting Rectal Suppositories
If possible, go to the toilet and empty bowels. Wash hands carefully with soap and warm water. Remove any foil or plastic wrapping from the suppository. Lubricate the tapered end of the suppository with a small amount of K-Y® Jelly. If the jelly is not available, moisten the suppository with a small amount of water. Either stand with one leg on a chair or lay on one side with one leg straight and the other leg bent toward your stomach. Separate buttocks to expose the rectal area. Gently but firmly push the suppository into the rectum until it passes the sphincter (about 1/2 to 1 inch in infants, and 1 inch in adults. Close your legs and sit (or lay) still for about 15 minutes. Avoid emptying bowels for at least one hour (unless the suppository is a laxative). Avoid excessive movement or exercise for at least one hour. Wash hands again with soap and warm water immediately after inserting the suppository.
Ex: Formulation 6 Rx Camphor 100g Starch 600g Zinc Oxide 300g M. Ft. Pulv. 10g Sig: p.a.a. b.i.d.
Mix and make powder
Manual Methods of Comminution (compounding): Define Comminution
Process of reducing particle size of a solid substance to a finer state of subdivision
USP 795
Regulatory Landscape of Non-Sterile Compounding
Preparation of suppositories: Fusion method - general procedure: Storage
Suppositories made from polyethylene glycol should be stored at usual room temperature without the requirement of refrigeration. Suppositories made from fatty (oleaginous) bases should be stored in the refrigerator and would require an auxiliary label, "refrigerate". Note: • The fusion process should be used carefully for thermolabile drugs and insoluble powders. • Insoluble drugs may separate from the melt depending on the density leading to non-uniformity in drug distribution.
Preparation of suppositories: 2. Fusion (molding) method:
The steps in molding include (a) melting the base, (b) incorporating any required medicaments, (c) pouring the melt into molds, (d) allowing the melt to cool and congeal into suppositories, and (e) removing the formed suppositories from the mold.
Topical dosage forms
These are designed to deliver drug into the skin in treating dermal disorders, with the skin as the target organ.
Transdermal dosage forms
These are designed to deliver drugs through the skin to the general circulation for systemic effects, with the skin not being the target organ
Total effervescent vehicle needed is ___ Citric acid = Tartaric acid = Sodium bicarbonate =
Total effervescent vehicle needed is 108 g Citric acid 16.875 g Tartaric acid 33.75 g Sodium bicarbonate 57.375 g
Provide examples of different types of pastes
Two official types: - Zinc Oxide Paste - Zinc Oxide and Salicylic Acid Paste. Others: - CMC Sodium Paste 17% (gel) - Magnesium Hydroxide Paste 33% (suspension) - Triamcinolone Acetonide Dental Paste is 0.1% (Paste of Pectin, Gelatin, Sodium CMC, Polyethylene, Mineral Oil, Guar Gum, and Tragacanth)
Inserting Vaginal Suppositories
Wash your hands carefully with soap and warm water. Remove any foil or plastic wrapping from suppository. Place suppository in applicator. Holdtheapplicatorbytheoppositeendfromwherethe suppository is. Either lay on your back with your knees bent or stand with your feet spread a few inches apart and your knees bent. Gently insert the applicator into the vagina as far as it will go comfortably. Once you are ready, push the inside of the applicator in and place the suppository as far back in the vagina as possible. Remove the applicator from the vagina. Wash your hands again with soap and warm water.
2. Bulk Powders Oral bulk powders:
bulk powders intended for oral administration
1. Divided Powders Oral divided powders (charts):
dispensed in folded powder papers as individual dose
2. Bulk Powders Douche powders:
dissolved in water prior to use as cleansing agents
Suppositories for Local Action Vaginal Suppositories
employed mainly as contraceptives, antiseptics in feminine hygiene (e.g., miconazole nitrate for fungal infections)
Suppositories for Systemic Action Vaginal Suppositories
intended for hormone replacement therapy (progesterone), contraceptive steroids (Etonogestrel+ethinyl estradiol= NuvaRing®), induction of labor (Dinoprostone= Cervidil®)
Suppositories for Systemic Action Rectal Suppositories
intended for several therapeutic activities including asthma, nausea, motion sickness, anxiety, migraine headaches, and bacterial infections.
M.Ft
mix and make
aa
of each
Pulv
powder
The individual doses of a divided powder in either folded powder papers or plastic packets are traditionally dispensed in a
powder paper box
2. Bulk Powders Dentifrice powders:
powder used in the cleaning of teeth
Define Ointments
semisolid dosage forms intended for external application to skin and mucus membranes - all semi-solids are ointments (creams and ointments)
Citric acid monohydrate alone results in a
sticky mixture that will not easily granulate
Tartaric acid is not used alone because
the granules are too friable and crumble
p.a.a.
to be applied to affected part
Suppositories for Local Action Urethral Suppositories
used as antibacterial and as local anesthetic preparative to urethral examination
Drug
• Active pharmaceutical ingredient (API)
Beyond Use Date: • Water containing (Ex: aqueous) oral preparations
• BUD 14 days when stored at controlled cold temperature
Beyond Use Date: • Water containing topical/dermal/mucosal liquids & semisolid preparations
• BUD 30 days
Beyond Use Date: • Nonaqueous preparations
• BUD not later than the time remaining until the earliest expiration date of any API, or 6 months, whichever is earlier
Differences in "Expiration Dates" 1. The expiration date for the medication order or prescription
• CII - No legal expiration date • CIII-IV - 6 months from the date the order was written • Non-Controlled - No legal expiration date
Effervescent Granules
• Contain mixtures of citric acid, tartaric acid, with a bicarbonate and a medicinal agent • Carbonated solution is a pleasant vehicle and lessens the bitter Citric acid: acidulant Tartaric acid: acidulant Sodium bicarbonate: source of CO2
Preparation of suppositories: 2. Fusion (molding) method: 2. Calibration of the mold:
• Every suppository base has different density and the added drug also affects the density of the mixture. So, to have the proper amount of the drug in a suppository the suppository mold has to be calibrated for each base.
Considerations for Rounding
• Ex: If using a syringe with graduation marks, you can only measure to the unit of the markings • Tablets should be rounded to the whole number •Depending on what you are calculating you may need to round up or down, not simply rely on the rule of <5 round down or > 5 round up •Ex: If calculating days supply and you calculate that you have a quantity sufficient for 2.6 days, you would NOT round up to 3 and say you have a 3 day supply. You would round down and say you have a 2 day supply because you do not have enough for a 3 day supply •Ex: If calculating the volume needed to dispense for an order to the whole mL and you calculate you need 10.4 mL, you would not round down and dispense 10 mL, you would round up and dispense 11 mL to ensure you dispensed enough
Label Instructions for Patients
• Include a verb in the directions (e.g. take, give, instill) • Indicate dosage form (e.g. tablet, capsule, ointment) • Use words instead of numbers • Specify route • Specify side if applicable (e.g. right eye, left ear) • Don't use abbreviations • Avoid use of teaspoons/ tablespoons (use mL)
Ointment bases: 1. Hydrocarbon bases (oleaginous bases) Advantages
• Inexpensive • Nonreactive, Nonirritating • Good emollient, protective, and occlusive properties • Are not water-washable so they stay on the skin for emollient/protective effects • Inert, no water, no microbes attack, highly stable • Water sensitive drugs can be included
Different Granule products: Prevacid (lansoprazole delayed-release suspension)
• It is enteric-coated granules • To prepare a dose, empty the packet contents into 30 mL of WATER • Prevacid products should not be crushed or chewed
Ointment bases: 4. Water Soluble Bases The numeric designations associated with PEGs refer to the average molecular weight of the polymer. MW <600 MW >1000 MW between 600-1000
• MW < 600 are clear, colorless liquids; • MW > 1000 are wax-like white materials; • MW between 600 and 1000 are semisolids.
Preparation of suppositories: 2. Fusion (molding) method: 1. Lubrication of the mold:
• Mineral oil is used as lubricant. Lubrication is not needed for cocoa butter and polyethylene glycol based suppositories as they contract sufficiently on cooling and separate out from the mold. Glycerinated gelatin suppositories need lubricant. Jay R, my personal experience is that lubrication would help in all cases.
Compounding Record Components
• Official or assigned name, strength, and dosage of the preparation • Master Formulation Record reference for the preparation • Names and quantities of all components • Sources, lot numbers, and expiration dates of components • Total quantity compounded • Name of the person who prepared the preparation, name of the person who performed the quality control procedures, and name of the compounder who approved the preparation • Date of preparation • Assigned control or prescription number • Assigned BUD • Duplicate label as described in the Master Formulation Record • Description of final preparation • Results of quality control procedures (e.g., weight range of filled capsules, pH of aqueous liquids) • Documentation of any quality control issues any any adverse reactions or preparation problems reported by the patient or caregiver
Ointment bases: 2. Absorption bases Disadvantages
• Poor patient acceptance because greasy nature and Lanolin-type bases are somewhat sticky and have unpleasant odor • Not easily removed with washing • Skin sensitizing • Compatibility problems • Chemical stability problems due to water • Microbial growth due to water, hence need a preservative.
Vaginal Inserts
• Since tablets are very inexpensive to manufacture, inserts are now more common than suppositories for commercial products for vaginal use. • Inserts are also less messy and easier to package and ship. The tablets are usually ovoid (shaped like an egg) and are supplied with a plastic inserter for placement of the tablet high into the vagina. • The patient should be instructed to dip the insert quickly into water prior to use. Inserts are made with the same excipients used to manufacture oral compressed tablets. Lactose is said to be commonly used as the diluent.
Beyond Use Date
• Stability of compounded preparation is generally not known • Cannot use a manufacturer's expiration date • Packaged in tight, light-resistant containers, stored at controlled room temperature • BUD cannot be later than expiration date of any ingredient used in preparation
Packaging Gels
• Store in air-tight container, refrigerated or room temperature such as in Tubes, jars, squeeze bottles or pump dispensers - some in Applicators or syringes • Gels should be observed for shrinkage, separation of liquid, discoloration, and microbial contamination - common preservatives: Benzalkonium chloride, sodium benzoate, methylparaben, propylparaben, thimersal
Packing and Storage of Suppositories
• Suppositories prepared with cocoa butter or fatty bases are packed individually to prevent contact and adhesion. Refrigeration is required. • Suppositories of photosensitive drug are packed in opaque metallic foil. • Suppositories made from polyethylene glycol bases may be stored at usual room temperature. Refrigeration is not required.
Progesterone vaginal suppositories RX: Progesterone, micronized powder q.s Polyethylene glycol 400 60% Polyethylene glycol 8000 40%
• The amount of progesterone per suppository ranges from 25 to 600 mg. The suppositories are used in treating luteal phase defect, premenstrual syndrome, luteal phase spotting, and in preparation of the endometrium for implantation
Formulation of vaginal suppositories: Buffered to an acid pH (usually about pH 4.5)
• This acidity discourages pathogenic organisms and provides a favorable environment for eventual recolonization by the acid-producing bacilli normally found in the vagina.
Differences in "Expiration Dates" 3. The expiration date of the compounded preparation
• This is the "Beyond Use Date" or "Do not use beyond date" determined from the date the preparation is compounded • You will learn how to determine this - See 795 for basic principles
Differences in "Expiration Dates" 2. The expiration date of each ingredient used to compound the preparation
• This is what will be on the bottle or container of each product
Define Blending (Mixing)
• Two or more powders are combined into a homogenous mixture. • homogenous mixture --> consistent dose
Urethral Suppositories
• Urethral suppositories, also called bougies, are slender and tapered (pencil-shaped), suppositories often about 5 mm in diameter and up to about 60 mm long. • These are intended for insertion into the male or female urethra and they have been used in the treatment of local infections. • A much smaller urethral suppository (micro-suppository) has been introduced for the administration of alprostadil in the treatment of erectile dysfunction. • The alprostadil urethral microsuppository (Vivus, Inc.) is a single-use medicated trans- urethral system for the delivery of alprostadil to the male urethra. • The drug is suspended in a polyethylene glycol 1450 excipient and is formed into a medicated pellet, or micro-suppository, measuring 1.4 mm diameter by 3 mm or 6 mm long. Available strengths are 125, 250, 500, and 1000 g. The micro-suppository resides in the tip of a translucent hollow applicator. It is administered by inserting the applicator tip into the urethra after urination. • The polyethylene glycol 1450 vehicle will dissolve in the available fluid, releasing the drug for absorption. The applicator system is composed of medical grade polypropylene; each system is individually foil packaged.
Effervescent Granules: Ratio of citric acid and tartaric acid
• citric acid monohydrate : 1 • tartaric acid : 2 • Sodium bicarbonate 3.4 g produces a powder with good effervescent properties.
Formulation of vaginal suppositories: Ingredients in vaginal suppositories
• combinations of the various molecular weight polyethylene glycols • surfactants • Parabens as preservative agents
Ointment bases: 4. Water Soluble Bases
• completely water soluble or water miscible • No oleaginous components are present • used for incorporation of solid APIs.
Advantages of Rectal Absorption
• has no taste limitations-particularly important with children. • Avoids or minimizes hepatic first-pass metabolism • Avoids hostile gastrointestinal environment for drugs that are susceptible to degradation by pH or gastric fluids/enzymes.
Different Granule products: Oral Products for Reconstitution
• most common use of granules as a finished prescription dosage form • Active ingredients intended for oral use that are unstable when dissolved or suspended in water (e.g., antibiotics) • The pharmacist reconstitutes these products with purified (e.g., distilled) water just prior to dispensing. • stable for 1 to 2 weeks when refrigerated vs dry granular form of the API is stable for 3 to 5 years • E.g., ZITHROMAX for oral suspension is supplied in bottles containing azithromycin dihydrate powder
Ointment bases: 3. Water-Removable Bases Advantages
• non-greasy and can be removed from skin by washing • can absorb some water or alcohol and thin out to a lotion. • allow dissipation of fluids from injured skin • shiny and aesthetically pleasing
Drug Product
•Active + inactive ingredients •Includes dosage form and strength •e.g. Metformin 500mg tablet (immediate release, extended release, etc.), Enoxaparin 80mg/0.8mL solution in a pre-filled syringe, Ibuprofen suspension 100mg/5mL
Strength
•Amount of drug (active ingredient) in one unit •e.g. 500mg tablet, syringe containing 80mg, suspension containing 5mg/mL (concentration)
Dose
•Amount of drug taken at one time (unless specified as "total daily dose") •e.g. 500mg tablet, 2 tablets → Dose = 1000mg 5mg/mL suspension, 5mL → Dose = 5 mL or 25mg
SIG
•Directions supplied by the prescriber to the pharmacist for interpretation •Should include information on dose, route, and frequency •e.g. Take 2 tablets by mouth BID Inject 80mg subcutaneously q12h
Instructions
•Directions the pharmacy places on the product for the patient •e.g. Take 2 tablets by mouth twice a day Take 1 tablet as needed for pain
Route
•How administered •e.g. PO, IV, Subcutaneously, SL, rectally, etc
Duration
•How long the drug is to be taken •Sometimes specified for acute therapies (e.g. antibiotics, may state "x 10 days") •Is not always provided •Can sometimes be determined based on the days supply but not always
Frequency
•How often •e.g. Daily, BID, PRN, etc
Non-Sterile Pharmaceutical Compounding Includes:
•Oral powders, tablets, capsules, lozenges •Oral solutions, suspensions*, emulsions •Rectal and vaginal suppositories •Topical creams, ointments*, pastes, and gels
Days Supply
•The number of total/complete days the amount dispensed to the patient will last •This will be based on the amount needed per dose, frequency, and duration •This is NOT the supply/amount per day
Quantity
•The total amount dispensed to the patient •May be in tablets, units, mL etc •Does NOT include amount provided by any refills