PSMA (PDDS)

COMPOUNDING AND MANUFACTURING

It is important but oftentimes difficult to distinguish between compounding and manufacturing

COMPOUNDING

• Small scale of production

• Preparation, mixing, assembling, packaging or labeling of a drugor device

• Result of a practitioner’s prescription drug order or initiativebased on the pharmacist/patient/prescriber relationship in thecourse of professional practice

• The purpose of, as in incident to research, teaching or chemicalanalysis and not for sale dispensing

• A true pharmaceutical service involves not only the redistributionof a commercially available commodity but also compoundingservice (e.g. paper tabs and parenterals)

EXTEMPORANEOUS COMPOUNDING

• It is defined as the timely preparation of a drug productaccording to a physician’s prescription, a drug formula, or arecipe in which amounts of the ingredients are calculated tomeet the needs of a particular patient or group of patients

• This is one of the professional functions or practices on apharmacy

• PURPOSE: Prepare an individualized drug treatment for aspecific patient based on an order from a duly licensedprescriber○ The fundamental difference between compounding andmanufacturing is the existence of apharmacist/prescriber/patient relationship that controls thecompounding of the drug preparation

• Compounded drugs are not for resale but, rather, are personaland responsive to the patient's immediate needs

• Although the need for extemporaneous compounding hasdecreased due to the availability of standardized commercialdrug products, the need for extemporaneous preparationscontinues especially in cases such as:

  • dispensing pediatric medications

  • it may be necessary to dilute standard adult strengths ofdrugs to obtain measurable doses.

  • combining topical products for use in dermatology: forexample, the use of a certain antibiotic with a specific antiinflammatoryagent

Compounded Prescription

a prescription fromphysicians order containing the ingredients andinstructions for compounding the preparation

MANUFACTURING

• Large scale production

• Production, preparation, propagation, conversion or processingof a drug or device, either directly or indirectly, by extraction fromsubstances of natural origin or independently by means ofchemical or biological synthesis, and includes any packaging orrepackaging of the substance(s) or labeling or relabeling of itscontainer, and the promotion and marketing of such drugs ordevices

• Includes the preparation and promotion of commerciallyavailable products from bulk compounds for resale bypharmacies, practitioners, or other persons

• Beaker

• Mortar and pestle

• Stirring rod

• Graduated cylinder

Equipment used in the Preparation of a Solution (Compounding)

• Mixers

• Filtration system

• Big containers

• Equipment used in the Preparation of a Solution (Manufacturing)

PREPARATION

The United States Pharmacopeia (USP) uses the term __ to refer to compounded prescriptions

PRODUCTS

The United States Pharmacopeia (USP) uses the term __ to refer to manufactured pharmaceuticals

COMPOUNDED PRESCRIPTION

A prescription with two or more components, requiringcompounding or mixing the components

1. ISOLATED PRESCRIPTION

2. ROUTINE PRESCRIPTION

3. BATCH PREPARED PRESCRIPTION

TYPES OF COMPOUNDED PRESCRIPTION

ISOLATED PRESCRIPTION

one that the pharmacist is not expecting to receive nor expecting to receive again

ROUTINE PRESCRIPTION

one that the pharmacist may expect to receive in the future ona routine basis, and there may be some benefit to productsquality to standardize preparations like this (Preparationprotocols on file)

BATCH PREPARED PRESCRIPTION

one of which multiple identical units are prepared as a singleoperation in anticipation of a receipt of prescription

• The pharmacist who will perform this should be capableand willing to do it properly

STEEF-CC

• Stability

• Training and experience of pharmacist

• Equipment

• Environmental/Compounding facility

• Formulas

• Compounding support

• Chemical supplies

FACTORS TO CONSIDER IN COMPOUNDING

STABILITY

The extent to which a preparation retains, within specified limitsand throughout its period of storage and use, the sameproperties and characteristics that it possessed at the time ofcompounding○ Consider:

• Chemical

• Physical

• Microbiological stability

beyond-use date

the time and date after which thecompounded product should not be stored nor transported

Expiration date

is the term for manufactured products

For non-aqueous liquids and solid formulations

The beyond-use date is not later than 25%of the time remaining until the product’s expiration date or 6 months, whichever is earlier

product with A USP or NF substance

The beyond-use date ≤ 6 months

water-containing formulations

The beyond-use date is not later than 14 dayswhen stored at cold temperatures

all other formulations

The beyond-use date is not later than intendedduration of therapy or 30 days, whichever isearlier unless there is a supporting valid scientificstability information applicable to the specificpreparation

6 months maximum BUD

BUD maximum of a non-aqueous formulation (eg, a capsule without water in it)

14 days under refrigeration maximum BUD

BUD maximum of an oral formulation containing water

30 days maximum BUD(Usually if it contains water, it isshorter beyond-use date becauseof possible microbialcontamination)

BUD maximum of a topical containing water (eg, ointment)

Freezer

between -25ᵒC and -10ᵒC

Cold temperature

not exceeding 8ᵒC

Refrigerator

thermostatically controlled between 2ᵒC and 8ᵒC

Cool temperature

between 8ᵒC and 15ᵒC

Controlled room temperature

thermostatically controlled between 20ᵒC and 25ᵒC with allowed excursions between 15ᵒC to 30ᵒC

EQUIPMENT

• Based on the type and extent of the services one chooses toprovide

• Equipment surfaces that come in contract with ingredients orcompounded preparations should not be reactive, additive, orsorptive so that the purity of the preparation is not compromised

LAMINAR FLOW HOOD

• for aseptic compounding of sterile solutions

• used to maintain the number of the particulates flowing in the air

REFRIGERATOR

to maintain temperatures as specified in the USP

BALANCE

• instrument for determining the relative weights of substances

• should be selected correctly for the specific task at hand

• used skillfully and should know the type of balance that will beuse and how to read the numbers included in the balanceespecially if it is digital

• protected from damage

• checked periodically

• Single-beam (equal-arm or unequal arm)

• Compound lever

• Torsion

• Electronic

classification of balance

CLASS A OR CLASS III PRESCRIPTION BALANCES

• used to weigh up to 60 grams of the ingredientdepending on the stated capacity

• other balances may be used, provided theygive equivalent or better accuracy – likeelectronic single-pan balance

• all prescription departments, like in a hospitalpharmacy they must have class III balance

PRESCRIPTION BALANCES

• uses the taut wire frame ortorsion principle

• a class III balance

• have a maximum maintenancesensitivity of 6 mg with no loadand with full load, used to weighquantities up to 60g

ELECTRONIC BALANCES

typically this are the type of balances that havethe sensitivity of less than 10mg. Most accuratecompared to class III balance

CAPACITY

maximum weight that can be placed on the balance pan

SENSITIVITY

sensitivity requirement or sensitivity reciprocal ; the smallest weight that gives a perceptible change in the indicating element

READABILITY

• In electronic balance, the smallest weightincrement that can be read on the digital display ofthe balance (eg. 0.001 g)

• On double-pan balance, the smallest weightincrement determined by the value of a hash-markon the graduated dial or weigh beam (eg. on metricscale of the dial, each mark = 0.01 g)

PRECISION

reproducibility of the weighingmeasurement as expressed by a standard deviation

ACCURACY

closeness of the displayed weight as measured by the balance, to the true weight

5%

The United States Pharmacopoeia, they allow apercentage or the maximum error of __ % on a single wayoperation since the sensitivity of the balance represent theabsolute error in using that balance. So, the percentageerror will depend the amount of the drug weight, and willincrease as the amount of the drug decreases

mg

Sensitivity Requirement (SR)

WEIGHING DISH

• usually made of aluminum or polystyrene plastic, with capacityof 5 to 250ml

• very handy and the securely contain substances being weighed

• useful for weighing liquids because they have rigid sides

• more expensive than weighing papers

WEIGHING PAPER

usually for powders

GLASSINE PAPER

• preferred and recommended

• has surface that does not absorb materialsplaced on them

• drugs and chemicals are easily slipped off forcomplete transfer

PARCHMENT PAPER

• more acceptable for most purposes

• more absorbent than glassine and should notbe used for weighing thick liquids like coal tar

WAX PAPER

transparent and water-proof

SIMPLE BOND PAPER

usually used for dry powders

SPATULAS

• Stainless spatula with wooden or plastic handles

• Small double bladed, nickel stainless steel spatulas or micro spatulas

• Hard rubber or Teflon-coated stainless-steel spatulas

• Flexible rubber spatulas or rubber policeman or rubber scrapers

VOLUMETRIC DEVICES

• it is used to measure the solvent

• as the diameter of the graduate increases, the accuracy of the measurement decreases

TC

to contain that holds particular volume but will notdispense the exact volume (e.g. burettes and beakers)

TD

to deliver that dispense the volume indicated;designed to drain by gravity (e.g. pipettes)

Conical graduates

• are the easiest to use with wide mouths,and bases are the easiest to clean. Liquids may be stirred inthem with the aid of a stirring rod

• produce greater accuracy

FUNNELS

plastic or glass, with different capacities and different sternlengths and diameters

FUNNELS WITH NARROW STEM DIAMETER

• used for transferring solutions from onecontainer to another and not used for thickemulsions or suspensions

• used for filtering solutions

FUNNELS WITH SHORT LARGER DIAMETER STEMS OR POWDER FUNNELS

• used for transferring powder from mortars and other mixing vessels

• may also be used for transferring emulsions or suspensions

WEDGWOOD MORTARS

• ideal for particle size reduction and makingemulsions

• it should not be used for drugs that stain, drugspresent in small quantity, and very potent orhazardous drugs

PORCELAIN MORTARS

• have more attractive white glazed surface

• provide less shearing efficiency than wedgwood mortars and are less durable

CERAMIC MORTARS

• similar to wedgwood mortars but have abradant interior working surfaces and have similar uses and precautions

• less durable than wedgwood mortars

GLASS MORTARS

• commonly used in hospitals

• have smooth, non-porous interior surfaces

• useful for drugs that stain

• useful for making solutions and for diluting creamsto lotions

• preferred for triturating highly potent drugs and totriturate hazardous drugs

• effective as Wedgewood or ceramic mortars inreducing particle size of powder especially hardcrystals but not efficient for making emulsions andsuspensions

1. COMPONENT

2. ACTIVE INGREDIENT

3. ADJUVANT

4. GRADE OF INGREDIENTS

5. FLAVORANT

6. SOLVENTS

7. OILS

COMPOUNDING INGREDIENTS

COMPONENT

any ingredient for use in compounding a drug product

ACTIVE INGREDIENT

are chemicals, substances or other components of articlesintended for use in the diagnosis, cure, mitigation, treatment orprevention of diseases

ADJUVANT

“Excipients” or “Pharmaceutic aids”- inert ingredients or inactive ingredients

Primary standard

Highest purity and required for accuratevolumetric analysis

Spectroscopic Grade and Analytical Reagent

Very high purity

ACS

High purity; Conforms to minimumstandards set by the American Chemical Society

USP/NF

• Meets minimum purity standards: conforms to tolerance set by the USP/NFfor contaminants

  • USP - active ingredients

  • NF - inactive ingredients or adjuvant

CP

Refined, but still of unknown quality

Technical or commercial

Undetermined qu

Unofficial FCC

Certified to meet or exceed thespecification prescribed in the foodchemical codex

Food grade

Chemicals that have clearance for use inthe food

Cosmetic grade

For cosmetic purposes

FLAVORANT

imparts pleasant flavor and often odor to a preparation

• BLENDING

• OVERSHADOW

• PHYSICAL

• CHEMICAL

• PHYSIOLOGICAL

flavoring methodology:

BLENDING

blend different flavors; most common; appropriate for sour taste

OVERSHADOW

these are flavors with longer and stronger taste that are added to the obvious taste

PHYSICAL

formation of insoluble compounds of the offending drug

CHEMICAL

chemical reaction, such as adsorption or complexation

PHYSIOLOGICAL

anesthetizing the taste buds

• Chocolate

• anise

flavors for the taste (BITTER)

• Fruit

• berry

• vanilla

flavors for the taste (SWEET)

• Citrus

• root beer

• anise

• strawberry

flavors for the taste (SOUR)

• Butterscotch

• maple

• peach

• melon

• rasp berry

flavors for the taste (SALTY)

blending of flavors

appropriate flavoring methodology for medication with sour taste

blending, physiological, physical

appropriate flavoring methodology for medications with bitter taste

WATER

universal solvent, can dissolve both ionic andpolar solutes

AROMATIC WATER

most commonly used as flavoringagents; easily driven off from the solution and easily saltedoutby electrolytes

Organic compound

usually they are insoluble in water but the salt form of the drug is soluble in water

SYRUP

solvent, flavorant, used as medicinals

GLYCERIN

best solvent for phenols, iodine, boric acid, borates, tannic acid and cresol

ALCOHOL

good solvent for organic compounds such as alkaloids, glycosides, camphor, phenol, tannins, balsams resins and for some inorganic salts

ELIXIRS

not preferred for salts because it accentuates the saline tast

Aromatic elixir, NF

contains approximately 22% alcohol

Accentuates

emphasize saline taste

• Peanut

• Corn

• Sesame

• Mineral oil

are solvents used for IM injection