CPR 7 Ch 5 - Extemporaneous Prescription Compounding

(CPR 8 Ch 4)
First Part By Ahmed hashem
Compounding
Preparation, mixing, assembling,
packaging and labeling of a drug or
device in response to practitioners
prescription or initiative based on the
practitioner/ patient/ pharmacist
relationship triad.

Manufacturing
The production or processing of a
drug in a LARGE quantity by various
mechanisms.

Purpose

To prepare individual drug.

Mass production

Resale

Not for resale

Main legal regulation

State
State Boards of Pharmacy State
usually apply USP

Distributed to be sold to unknown

patients.
Federal
Food and Drug Administration FDA

USP term used

Stability determinant

Preparation
Beyond-use date

Definition

Products
Expiration date

Term extemporaneous used with compounding; it refers to on-demand preparation.

Compounding includes:Preparation of,

Drug dosage forms for both human and animal patients.

Drugs or devices in anticipation of prescription drug orders &for the
purposes of research.

Drugs and devices for prescribers office use

And Reconstitution or manipulation of commercial products that may
require addition of one or more ingredients.

Stability:
Beyond-use date (BUD):date after which a compounded preparation should not be used.
Non-Sterile Preparations:guidelines from USP Chapter 795 Pharmaceutical
CompoundingNonsterile Preparations

Sterile Preparations:Guidelines from USP chapter 797 Pharmaceutical

CompoundingSterile Preparations
All the following are in the absence of a program of sterility testingin place.
If sterility testing program is in place, the BUDs for nonsterile preparations.

These beyond-use dates for sterile and nonsterile preparations may be exceeded when
there is supporting valid scientific stability information, directly applicable to the specific
preparation.

Quality control:Guidelines for a quality control program are in USP chapter

1163 (Quality Assurance in Pharmaceutical Compounding)
Quality control testing: follows USP chapters 797 & 795
Pharmacist can do testing in-house or outsourcing it in laboratories,
In-house testing as weight, volume, PH, specific gravity, osmolality, physical
observations, sterility and endotoxins.
Out-sourced testing as sterility, endotoxins, potency, and dissolution.
Test results kept on file with compounding records for individual compounded preparations.

II. Requirements for compounding:

A. Source for chemicals and drugs: wholesalers or chemical supply houses.
Suppliers serve as compounding consultants to aid in ensuring their products
purity and quality.
B. Equipment: Appropriate standard operating procedures followed for
maintenance, operation, and calibration of equipment.
C. Location of compounding area: - Separate area in the pharmacy.
- Ideal location is away from heavy foot traffic, near a sink where there is
sufficient space to work and store chemicals and equipment.

- For compounding sterile preparations, laminar airflow hood and a clean

room, or isolation barrier technology equipment.
D. Sources of information: Library, references, journals, websites and
Drug product inserts; compounding specialty suppliers.
The USP states that compounded preparations must contain not less than 90% and not more
than 110% of theoretically calculated and labeled quantity of active ingredients.

III. Compounding of solutions:

Def: USP 34 defines solutions as liquid preparations contain one or more chemical
substances dispersed in a suitable solvent or mixture of miscible solvents.
Types of solutions:
1. Sterile parenteral and ophthalmic solutions require special considerations
2. Nonsterile solutions include oral, topical, and otic solutions.
Preparation of Solutions:the easiest to compound extemporaneously; a few rules followed:
1. Each drug is dissolved in solvent in which it is most soluble; solubility
characteristics must be known first.
2. If an alcoholic solution of a poorly water-soluble drug is used, the
aqueoussolution is added to maintain alcohol conc as high as possible.
3. The salt form of the drug is used, not the free acid or base form; both have
poor solubility.
4. Flavoring or sweetening agents as sucrose, aspartame, sorbitol, and cherry
syrup are prepared ahead of time and used to add flavor to solutions and
suspensions.
5. When adding a salt to a syrup, dissolve it in a few mL of water first; then
add to the volume.
6. Proper vehicle (e.g. syrup, elixir, aromatic water, purified water) selected.
7. Buffers are used to adjust PH of the solution to improve solubilityor
stability as citrate, acetate, phosphate.
Examples 1:
100 mg of Triamcinolone acetonide (M.wt. 434.5) is administered, determine the
amount of triamcinolone (M.wt. 394.4) in this dose?
434.5 g of Triamcinolone acetate corresponds to 394.4 g of Triamcinolone so,
1 g of Triamcinolone acetate corresponds to 394.4/434.5 of Triamcinolone so,
100 mg or 0.1 g of Triamcinolone acetate corresponds to (394.4/434.5) 100mg or 0.1 g
Triamcinolone = 91 mg of triamcinolone

Example 2:
Note: Normality, N, is the # of mEq of solute in 1 mL of solution.
Equivalent wt. = M.wt./ valence
Medication order:
KCl
1 mEq/mL
Preserved flavored, oral vehicle, q.s. 100 mL
M.wt. of KCl is 74.5 g

Eq wt. = 74.5/1= 74.5 g ---> 1 mEq= 74.5/1000= 0.0745g ---->

So, we have 0.0745 g KCl in ---->1 mL
X in-----> 100 mL
KCl required= 0.0745 x 100= 7.45 g
Molarity, Molar conc, M of solution is the # of moles of solute in one L of solution.

A mole is the molecular weight of a substance in grams.

The wt. of one mole of KCl= M.wt= 74.5 g
Since total wt of KCl is 74.5 g. So, there are  74.5g/ 74.5g= 1 mole of KCl -->Molar conc = 1
Example 3:
Salicylic acid
2%
Lactic acid
6 mL
Flexible collodion, a.d. 30 mL
<---- (caution; extremely
flammable)
Salicylic acid 2%; 2 g in -----> 100 mL
X in -----> 30 mL
X= 2 x 30 / 100= 0.6 g
> For Iodine preparation, a rubber or plastic spatula is used; Iodine is
corrosive.

IV. Compounding of suspensions:

Suspensions are defined by USP 34 as liquid preparations that consist of solid
particles dispersed in a liquid where particles are not soluble.
General Characteristics:
1. Some suspensions should contain antimicrobial agent as a preservative.
2. Particles settle in suspensions even when a suspending agent is added;
must be well shaken before use to ensure distribution of particles for a
uniform dose. 3. Tight containers are necessary for stability.
Principles to keep in mind when compounding:
Insoluble powders small and uniform in size to decrease settling &
suspension viscous&Topical suspensions smooth texture & Oral
suspensions pleasant odor and taste.

Formation of suspensions:
Suspensions are easy to compound; but physical stability is concern. To minimize stability
problem:

1. Particle size of all powders reduced2. Thickening (suspending) agent used

to increase viscosity, including alginic acid, bentonite, VEEGUM,
methylcellulose, and tragacanth.
3. Levigatingagent aid dispersion of insoluble particles, including glycerin,
propylene glycol, alcohol, syrups, and water.

4. Flavoring agents and preservatives added if the preparation is intended for

oral use. Preservatives asmethylparaben, propylparaben, benzoic acid, and
sodium benzoate. Flavoring agents any flavored syrup or concentrate.

5. Source of the active ingredients (e.g., bulk powders vs. tablets or capsules);

if commercial dosage forms are used, inactive ingredients considered &only

immediate-release tablets or capsules should be used not modified release,
unless necessary.

Preparation of suspensions:
1. Insoluble powderstriturated to a fine powder ---> add a small portion of
levigating agent liquid and powders are triturated until a smooth paste is
formed ---> add vehicle containingsuspending agentto required volume.
2. Final mixture transferred totight bottle for dispensing to the patient.
3. dispensed with a shake well label.Suspensions are not filtered.
5. Water-soluble ingredients, including flavoring agents, mixed in the
vehicle before mixing with the insoluble ingredients.
Example 1:
Propranolol HCl
4 mg/mL
Disp
30 mL
Sig:
1 mL p.o.t.i.d.
Calculations: Propranolol HCl: 4 mg/mL X 30 mL =120 mg.
Propranolol HCl --->powder or in immediate-release and extended-release dosage forms. Only
powder or immediate-release tablets used for compounding prescriptions; propranolol HCl
tablets yields 120-mg active drug (e.g., 3 X 40-mg tablets) used.
Compounding procedure: The propranolol tablets reduced to a fine powder in a mortar --->
levigated to a smooth paste, using 2% methylcellulose solution ---> add 10 mL of a suitable
flavoring agent ---> Mixture is transferred to calibrated container and brought to final volume
with purified water or suitable suspending vehicle. A shake well label is attached to the
prescription container.

Second Part ByAnilaSiddiqui

Emulsions
Two phase system: One liquid dispersed in another liquid as droplets.
`usedetxternally: as lotion & creams internally: mask the taste of medication.
Two liquids in an emulsion ----> immiscible ----> require emusifying agent.
Classified as:
Oil-in-water (o/w) or water-in oil (w/o)
Multiple emulsions:
Oil-in-water-in-oil (o/w/o)
Water-in-oil-water (w/o/w)
Emulsion gels: External phase of an oil-in-water is thickened with a gelling agent.
Unstable ----> Steps to prevent the 2 phases seperate into layers:
- Correct proportion of oil and water ( Internal phase ----> 40% - 60% of the total
- Emulsifying agent.
- Hand homogenizer ----> reduces the size of globules.
- Preservatives (generally methylparaben 0.2% + prpylparaben 0.02%)
- Shake well label.
- Protected from light & temp.
Emulsifying agents
Gums ----> Acacia or tragacanth ---->internal adm. ----> o/w
Methylcellulose &Carboxymethylcellulose----> o/w
Soap ----> external prep. ----> o/w & w/o
Non ionic emulsifying agent ----> o/w & w/o
Formation & preparation of emulsions
Mortar & pestle : Trituration > 5mins ----> coarse emulsions
Electric mixer & hand homogenizers are then used.
Order of mixing : depends on

volume.

- Type of emulsion (o/w or w/o), Emulsifying agent, Method of compounding.

a.Dry gum ( continental) method
b.Wet gum ( English) method
c.Bottle method
natural emulsifying agent ---> require specific order of mixing

--->All 3 use

d.Beaker method
---> Use synthetic emulsifying agent ---> regardless of the order of mixing
Preservative :must be soluble in water phase.
Flavoring agent :to mask the tasre of oil phase to the external phase before emulsification.
*(Do Table 5-2 from book)
Powdered dosage forms
Intimate mixture of drug, finely divided drug &/or chemicals intended for internal ( oral) or external (
topical) use.
Types : Powder papers, bulk pds, & insufflations.
Used when stability & solubility is concerned or too bulky to make into caps.
Unpleasant tasting, rapid deterioration.
Blending
Trituration in mortar ----> stirring with spatula ----> sifting ----> geometric dilution ( if needed).
For pulverization : mortar & pestle ( preferably wedgwood)
For light pds : sifting method ( repeat 3 - 4 times)
Preparation
Bulk Pds: dusting pds, douche pds, laxative, antacids, and insufflationpds.
Pulverization ----> blending ----> dispense in appropriate container.
Hygroscopic/effervescent ----> in tight or wide mouth jar.
Dusting pds ----> container with a sifter top.
Eutectic mixtures of pds ----> may liquify ----> add an inert pd( magnesium oxide) to separate the
eutectic materials.
Powder paper( dividedpds)
Blend entire pd ---->weighind. dose ----> transfer onto a pd paper ----> fold ----> dispense in a pd box (
not child resistant).

For hygroscopic/effervescent ----> glassine paper as inside linning.

*(do examples from book)
Capsules ----> solid dosage form
Drug enclosed in a hard or soft soluble shell ( usually of gelatin).
*( Do Table 5-4)
Capsule sizes
In humans: 5 (smallest) to 000 ( largest)
0 ----> largest suitable oral size.
In veterinarians: 10 ( 30mg), 11 (15mg) & 12 (7.5mg).
Preparation of hard & soft caps
Bulk pds ---->Triturate all the ing. ----> blending ----> filling using punch method.
On small scale: caps filling machine ----> 100 - 300 caps at a time.
*( Example 1)

Third Part ByNada Fouad

Viii: MOLDED TABLET (TABLETS TRITURATES):
DEF: small cylindrical molded or compressed tablets
PREPERATION: 1-powder moistened w alc and water
2-sintering process
For potent drugs in small doses and for rapidly disintegrating/dissolving dosage form
A- Using moistened powders
1. Special molds (pegboard, perforated plate)
2. Diluent: lactose/sucrose (80:20),moistening agent(ethyl alc/water(60:40)
3. Triturate diluents w active ingredients paste spread into mold tablets are
punched out dry on pegs
Active ing and diluents are mixed by geometric dilution
http://pharmlabs.unc.edu/video1.php?table_triturates.flv

Notes on calculation
If we want to make 500 tablets cont 200 mg atropine sulphate and the mold prepares 70 mg, so
for the 500 tablets we need 70*500=35000mg=35 gm which will contain 200 mg atropine +34.8
diluent(80 % of 34.8=28 gm lactose ,20% of 34.8 gm =6.8 gm sucrose)
B-Sintering process:
For materials w tolerate heat to 100 C
Mixture of active drug and diluents (mannitol +lactose) (65% of tab wt) blended
Triturated with PEG 3350tamped in moldoven (90 C,15-20 min)cool dispense in the
mold or removed packaged and labeled
http://www.youtube.com/watch?v=ZTvp--u_41M

IX.OINTMENTS,CREAMS,PASTES,AND GELS
Oint/cream/pastes: semi-solid, topical (local effect,release medication to penetrate the skin,
systemic effect)

Oint: oleaginous, creams: o/w or w/o emulsions, pastes: high content of solid (25%)
Gels (jellies): susp of small inorganic particles or large org molecules interpenetrated by a liquid
Types of oint bases:
1-hydrophobic

2- hydrophilic (emulsion base)

PREPARATION:
1-liquids are incorporated by gradual adding to absorption type base and mix
2-insoluble powders are reduced to fine powder then added to the base using geometric
dilution
3-water soluble substances r dissolved in water then incorporated to the base
4the final prep should be smooth
Notes: external use label
Examples in the book very imp CALCULATIONS
Example
a. Medication order
Sulfur
Salicylic acid, a.a. 600 mg
White petrolatum, a.d. 30 g
Sig: Apply t.i.d.
b. Compounding procedure.The particle sizes of the sulfur and salicylic acid are reduced
separately in a Wedgwood mortar and then blended together. Using a pill tile, the powder
mixture is levigated with the base. Using geometric dilution, the base and powders are blended to
the final weight. An ointment jar or plastic tube is used for dispensing, and an external use
only label is placed on the container.
Alternate method.Suppose you have sulfur 5% in white petrolatum ointment and a salicylic acid
5% ointment. How can you prepare the prescription using these and diluting withwhite
petrolatum?
Since we are using two different 5% ointments, two parts of each, this leaves one part for the
white petrolatum. A total of five parts is to be used to make 30 g (6 g per part): two
parts (12 g) of the sulfur 5%, two parts (12 g) of the salicylic acid 5%, and one part (6 g) of the
white petrolatum could be used. To check:
12 g x 0.05 = 600 mg of sulfur
12 g x 0.05 = 600 mg of salicylic acid
12 g + 12 g + 6 g = 30 g
X-SUPPOSITORIES:
Supp bases:

1-cocoa butter (theobroma oil):fat soluble triglycerides(witepsol),rectal

2-PEG(CARBOWAX):water soluble, vaginal and rectal(polybase)
3-glycerinated gelatin: water miscible(vag ,rectal)
Supp molds:
Rubber, plastic, brass, stainless steel,
Methods of prep:
1-molded sup (melt the base, incorporate the medication uniformly into it, poured into mold,
fusion method)
2-hand rolled supp
Storage: refrigerate label if appropriate, store in cool dry place
Example
a. Medication order
Naproxen suppository 500 mg
Disp #12
Sig: Insert u.d. into rectum
b. Calculations. Each standard adult suppository should weigh 2 g, but it depends on the mold
used and should be calibrated before compounding. Also, the displacement must be determined
for the added powder.
2 g (total weight) _ 0.540 g (weight of base displaced by the 500-mg tablet) per suppository
_ 1.46 g cocoa butter per suppository _ 13 suppositories
_ 18.98 g cocoa butter
c. Compounding procedure. Th e 13 naproxen 500-mg tablets are triturated to a fi ne powder,
using a Wedgwood or porcelain mortar. Th e 18.98 g cocoa butter base is melted in a beaker,
using a water bath. Th e temperature of the water bath should not exceed 36C. Th e powder is
then added and stirred until mixed. Th e mixture is poured into an appropriate rectal suppository
mold (about 2 g per suppository) and placed into a refrigerator until the suppositories
congeal. Any excess is scraped from the top of the mold, and a suppository box is used for

dispensing. A refrigerate label is placed on the box.

XI-STERILE PREPARATIONS:
General requirements:
PROPER: equipment, sullpies, facilities (laminar air flow, clean room, barrier technology
equipment), documentation, quality control, storage, labeling, knowledge of stability and
incompatibilities, knowledge of ancillary equipment
COMPOUNDING OF PARENTERAL PREP:
1-clean,aseptic techniques
2-knowledge of correct diluents for dry powder for reconstitution

3-stability and compatibility of further diluted solutions

RECONSTITUITION OF A DRY POWDER FROM A VIAL
1-clean env,aseptic technique
2-knowledge of required volume of diluents
3-approptiate needle size and syringe
4-surface of diluent container is cleaned w alcohol pad(wait to be evaporated) and fill the
syringe w the proper volume
5-surface of vial containing the powder is cleaned, inject the diluent into it
6-shake or roll to dissolve, invert the vial and withdraw the required volume
7-swab the medication port of the bagor bottle (vehicle) and inject the solution into it(don't
puncture the sidewall of the plastic container w the tip of the needle)
8-skake,knead or rotate to mix
9-check for particular matter, apply a sterile seal over the port
10-discard all needles and syringes
11-label
REMOVING THE FLUID CONTENT FROM AN AMPULE:
Note:
If the solution is for an intravenous push (bolus injection), the fi lter needle is removed from the
syringe and replaced with a cap.
If the solution is for an intravenous infusion, then the filter needle is removed and replaced with
a new needle of the appropriate size. The drug is injected into the appropriate vehicle.
REMOVING DRUG SOLUTION FROM A VIAL:
Note:
An equivalent amount of sterile air is injected into the vial to prevent a negative vacuum from
being created and to allow the drug to be removed
Examlpes
Please look at the book