Hospital Topics

ISSN: 0018-5868 (Print) 1939-9278 (Online) Journal homepage: https://www.tandfonline.com/loi/vhos20

the LAB: Rx: Stability After Reconstitution of Some

Parenteral Products, with Related Problems

Robert C. Bogash & Edward Egol

To cite this article: Robert C. Bogash & Edward Egol (1963) the LAB: Rx: Stability After
Reconstitution of Some Parenteral Products, with Related Problems, Hospital Topics, 41:10, 75-79,
DOI: 10.1080/00185868.1963.12082697

To link to this article: https://doi.org/10.1080/00185868.1963.12082697

Published online: 27 Nov 2019.

Submit your article to this journal

View related articles

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=vhos20
Stability After Reconstitution of Some
Parenteral Products, with Related Problems
By Robert C. Bogash and Edward Egol
• Mr. Bogash is pharmacy editor of
Topics;- Mr. EgoZ is pharmacist-in-
charge, LeRoy Hospital, New York
City.
Drugs that require reconstitution*
present stability problems that more
and more involve and concern hos-
pital pharmacists.
For this discussion such products
are classified as:
1) Parenteral-Penicillin G potas-
sium buffered, for injection, 5 mil-
lion units.
• American Collegiate Dictionary defines
reconstitute as, to constitute again; recon-
struct; recompose. In pharmaceutical par-
lance, It implies the addition of a liquid
diluent to a powder, usually forming a so-
lution or suspension.
October, 1963
2) Oral-phenoxymethyl Penicil-
lin (Penicillin V) for oral suspen-
sion, 125 mg./5 ml/ after reconsti-
tution.
3) Topical-thrombin topical, 5,-
000 NIH units, sterile powder.
Reconstituting a pharmaceutical
product is neither an unusual or
difficult manipulation for a practic-
ing pharmacist. Whether he prac-
tices in a hospital or a community
store, he is reconstituting an in-
creasing number of products before
dispensing them. Dispensing in this
context implies a) as a prescription
to or for a specific person, and b)
on proper requisition, as floor-stock
issue for a number of patients. Main-
ly, he reconstitutes trade-marked
products marketed for oral and topi-
cal use. Each container has explicit
directions for reconstitution and in-
formation about the resultant mix-
ture's stability.
Oral and Topical
Products of this nature are almost
always reconstituted by the pharma-
cist, who prepares and dispenses a
stable product having legible and
adequate directions for use, storage,
and warning-expiration date. As he
dispenses it, of course, pharmaceuti-
cal control is lost; he has no assur-
ance that product stability will be
maintained (improper storage) any
more than he can be certain the
product will not be used after its
labeled expiration date.
Parenteral
Parenteral products reqUlrmg re-
constitution pose a different, more
75
 complex problem, particularly in
hospital practice. Numerous factors
make parenterals different. Gener-
alizing somewhat, the most salient
are those of organizational and en-
vironmental origin. Some of the
more important are:
1) In contemporary practice, the
pharmacist has little more than an
intermediary role in handling paren-
teral products. He is, so to speak,
a middleman. He may do any or all
of the following: purchase, receive,
store, inventory, analyze, and dis-
pense-but rarely does he re-
constitute, dilute, or compound these
products. Compound here implies
adding one or more small-volume
parenteral products to a large-vol-
ume sterile solution for intravenous
use. It also implies preparing one or
more small-volume parenteral prod-
ucts in the same syringe for intra-
muscular use.
2) Reconstitution, dilution and
compounding are done usually on a
nursing station. Any or all may be
done by a variety of persons, in-
cluding registered or student nurses,
licensed practical nurses, and phy-
sicians (interns, residents, attending,
visiting or courtesy staff mem-
bers).
3) Hospital pharmacists have not
shown a keen or continued interest
in this work-a-day problem shared
traditionally by the nursing and
medical staffs.
4) Nationally, many hospitals do
not have a pharmacy department;
some do not even have a formal
understanding with a community
pharmacy.
5) Comparatively few established
hospital pharmacies are adequately
staffed for extended-hour service,
let alone around-the-clock service.
And, hospital pharmacists generally
are neither psychologically oriented
nor conditioned for extended hours
of coverage.
What, then, happened to spur the
pharmacist's interest and concern
in this area? Some of the more overt
reasons .appear to be:
a) Pharmaceutical research and
technology deliver an increasing
number of therapeutic agents that
are marketed as sterile powders, to
be reconstituted before administra-
tion (injection). Most of these could
not be marketed with a reasonable
prediction of shelf-life stability ex-
cept as powders.
b) Improved technology may war-

76 For further information see postcard opposite page 142. Hospital Topics
rant reformulating an existing prod- STABILITY AFTER RECONSTITUTION OF SOME PARENTERAL PRODUCTS
uct. The result could be better ab- Legend: Na -Sodium HC1 - Hydrochloride
sorption and higher potency (Micro- K - Potassium so, - Sulfate
Co -Calcium Refrigerate--2·1 O'C (35.6-50'Fl
nized Guseofulvin), increased sta- Zn - Zinc Room Temperature--21.5·25'C (70·77'F)
bility (smallpox vaccine, dried; Remarks
Nonproprietary Trade name(s) Stability after
Dryvax® Wyeth), extended phar- name[s) reconstitution
macologic action (Spansules<TMI Amphotericin 8 Fungi zone 5 mg/ml sol'n, 24 To avoid precipitation
for infusion (Rl hours in a dark room; the Infusion should be
Smith, Kline & French), greater 7 days at 2-10° keel at eH 5.5
product acceptability (chloral hy- Bacitracin Uejohn 14 days at 2·10' Decomposes quickly
at room temperature,
7 days at 2-10'
drate capsules), or possibly better Pflzer
also loses 10% potency
at pH 5-7
functional design (loaded syringe
Chloramphenicol Chloromxcetin IRI 30 days at room temp.
and Tine Test) . Chlortetracycline HC1 Aureomycin I R) Less than 24 hours at Use freshly made
solution
c) Recent studies of drug distri- 2-10'
Avoid shaking
Colistimethate Sodium Coly-Mycin IRl 7 days in a cool
bution systems in hospitals indicate injectabl• place
Most stable between
there are many more medication er- Erythromycin
Glucoheptonate
llotycin IR) 7 days at 2-10'
pH 6·8; deterioration
rors (deviations from the physician's below pH 4
Erythromycin Erythrocin IRI 14 days ot 2-10'
written orders) committed than are lodobionate
reported. 1 • 2 Methicillin Sodium Dimocillin IR)
Staphcillin IRI
24 hours at room
temp., 4 days at
d) Periodic inspection of nursing 2-10°
IR) 2 years at room temp. Keep in refrigerator to
stations supplies often yields mul- Neomycin Sulfate Mycifradin
prevent discoloration
tiple-dose vials of reconstituted Nitrofurantoin Sodium Furodantin IR) 2 weeks at room temp. Solution should
just before use
be mixed
Sodium
drugs dispensed for a specific patient Novobiocin Sodium Albamxcin jRI Use within 48 hours
from which fractional doses have Cothomycin IRI Use only freshly pre-
pared solution
been withdrawn. Often the remain- Oleandomycin Malromlcin IRI 7 days at room temp.
der is saved in anticipation of using Oxacillin Sodium Dimocillin RT IRI 24 hours at room
temp., 4 days at
it for either the same or a differ- 2-10°
ent patient. Oxytetracycline Terramycin IRl 48 hours at 2-10'
Penicillinase Neulrapen IRl 7 daxs at 2·10"
e) Some floor-stock issue is re- Penicillin G 3 days at 2-10'
constituted to be administered over Potassium
Penicillin G 7 days at 2-10'
varying periods of time to different Potassium buffered
patients. Theobarbiturates and suc- Penicillin 0
Sodium
Cer·o·Cillin IR) 21 days at 2-10'

cinylcholine hydrochloride being ex- Polymixin 8 Sulfate Aerosporin (RI I year at room temp. Deteriorates in either
I hi!!h or low pH
amples for anesthesiology. Many Ristocetin Sponlin IR) 30 days at 2-10' at Alkalinity causes
similar solutions of different poten- pH 5·7 deterioration
Streptomycin Sulfate Parke-Davis 30 days at room Discoloration does not
cies prepared by different anesthe- temp., 90 days at indicate a loss of
2-10° potency
siologists are stored in the same Achromycin IM IR!
Tetracycline 24 hours at room temp.
place. The rapidity of turnover could Hydroch Iori de Achromycin IV IRI 24 hours at room teme.
affect stability. Panmycin IV IR) 24 hours at room teme.
Steclin jRJ 24 hours at room teme.
f) Intravenous solutions are not
'"
Tetracycline Phosphate Sumycin jR! hours at room teme.
usually prepared just before they Tetrex IR!
are started. Often they contain one Rolitetracycline Velocycline IRI 6 hours at room temp.,
24 hours at 2-10°
or more therapeutic agents (recon- Vancomycin Vancocin jR! 14 days at raam teme.
Viocin jR)
stituted). The time elapsed between Viomycin 7 daxs at 2-10'
5 gram viols to be di-

.
Vinactane (R) 7 days at room temp.
preparing and starting a venocyclis luted with at least 8.5
mi. H.O and stored in
depends on several variables, which refriierator
are not subjects of this discussion. Acetozolam ide Diamox IR! 3 weeks at room temp.
Amobarbital Sodium Amytal Sodium IRI Prepare solution im-
What is important is that the elasped mediately before use
time is known to sometimes exceed Angiotensin Amide Hypertensin IRI It is stable for no
longer than 30 days
Further dilution
sory
is neces-

the point of assured stability. This if kept in original

vial and stored at
can be complicated by failing to give ~R'F.
HC1 IR)
maximum protection to the pre- Chlordiazepoxide librium Prepare
mediately
solution lm· Use special diluent sup-
before use; plied
pared solution, thereby hastening discard unused solution
Ch forth iazide Diuril IRI 24 hours at room temp. Do not refrigerate
degradation (amphotericin B left in Conjugated Estrogens Premarin IV IRI 60-90 days at room Keep away from light
direct sunlight, for instance.) temp.
Corticotropin Adhar IRI
g) A break in aseptic technic can Cyclophosphamide Cytoxan IR) Prepare fresh solu· Powder should be pro-
contaminate a multiple-dose vial. tion lor use up to 3 tected from temp. above
hours after prepare- 90'F.
We know some drugs, especially or- tion.

ganics, are affected adversely by cer- Diphenylhydantoin Dilantin Should be used within Haze and precipitate de·
Sodium Sodium IRI a few hours-use only velop s1owly
tain microorganisms. Dextrose in- a clear solution
Fibrinolysin & Elase IRl Should be prepared
jection by yeasts and cyanocobala- Desoxyribonucleose just before use
min (vitamin B12) by some bacteria fibrinolysin, Human Adose IR) Administration should
be completed within
are examples. 2 hours af reconstitution
IRI Administration should 10% in 2 hours
h) Hospital pharmacists often get Thrombolysin
be completed within
loses
25% in 4 hours
unusual requests for patients who 2 hours of reconstitution
Hydrocortisone Salu·Cortef I Rl 24 houn at room temp. Both 100 mg. and 250
are unable to tolerate either the Sodium Succinate
- mg. vials

78 Hospital Topics
Nonproprietary Trade name(s) Stability after Remarks i) Currently, package inserts con-
name{s) reconstitution tain much more data than ever be-
Hydroxydione Sodium Viadril Sodium (RI Solutions should always After standing several fore. Still, some fall short, failing
be freshly prepared hours, free hydroxydione
may precipitate to include mention of stability after
Mechlorethamine HCT Mustorgen (R) HC1 Rapid deterioration
once reconstituted;
Neutralize tubing & vial
with sodium thiosulfate
reconstitution and how the result-
use only freshly prepared sol'n. ant solution is best stored, if at all.
solution
Mercaptomerin Sodium Thiomerin Sodium Store below 15°C. Further, as researchers 3 collect
Methohexital Sodium Brevital Sodium (R) As long as solution Often up to 6 weeks more data about how drug prod-
remains clear
Methotrexate Methotrexate (R) 2 weeks at room temp. Use water for injector ucts are handled on the nursing
(formerly called
amethopterin)
If precipitate forms
before, discard sol'n. stations, we learn of practices and
Methylphenidate HC1 Ritalin (R) 2 months at room problems that require pharmacists'
temp.
Methylprednisolone Solu-Medrol (R) 24 hours at room temp. attention and help. Such aid can
Sodium Succinate
Pancreatic Dornase
be an increased sense of awareness
Dornovac (R) 'Prepare immediately
?afore use; discard sharpened by functional reminders
unused solution
Phenobartibal Sodium luminal Sodium (R) Prepare fresh solution; Use cool sterile water as
in the form of charts or newsletters.
discard after 24-.48 diluent It is for the latter purpose that
hours
Phentolom ine Regitine (R) 6 months after the accompanying chart was com-
Methonesulfonote
Prednisolone Soluble Meticortilone (R)
reconstitution
piled. It reflects information collect-
Use immediately
Soluble ed from three sources: publications,
Secobarbital Sodium Seconal Sodium (R) Prepore solution im-
mediately before use
communication with the manufac-
Streptokinase-
Streptodornase
Varidase (R) I week at 2·10', If solutions become opal- turer and, to a lesser extent, assay
Topical ascent due to calcium in
water they may still be procedures done either by or for
Varidase (R) IM I week at 2·10'
used
us. We hope the chart may be of
Varidase (R) Jelly 2 weeks at 2-10' At room temp. prepare- aid as a starting point for others to
will not remain
tions
stable for more than 24 use, revise and expand. Any contri-
Succinylcholine HCJ Anectine (R) HC1
hours bution to resolving the over-all
20 mg/ml-5 months Refrigeration of Anectine
at room temp. sol'ns prevents loss of problem can enhance patient care
50 mg/ml-3'12 months potency, see company bro-
at room temp. chure and safety as they apply to drug
100 mg/ml-2'12
at room temp.
months
therapy. Also, it could give para-
Thiopental Sodium Pentothal (R) medical personnel and hospital man-
Sodium
Thiamylol Sodium Suritol (R) Sodium Prepare just before Only clear sol'ns should agement a measure of comfort in
use, use within 48
hours
be used knowing a sensitive and sometimes
Thrombin Topical
Use sol'ns on some questionable practice was being up-
day prepared; keep
refrigerated, preferably graded.
frozen if several hours
are to elapse before use
We believe our experience is not
of On:k: eortion unique in hospital pharmacy prac-
Tolbutamide Sodium Orinase (R) Sodium Use within 1 hour after
reconstitution tice. We know many hospital phar-
Trypsin Crystallized Parenzyme (R)
Agueous
3 months at 2-10~ macists nationally, in hospitals of all
Urea lyophilized Urevert (R) Use only freshly prepared Discord unused portions sizes, who are involved with these
Urea phil (R)
sol'ns
Use only freshly prepared Discord unused portions
problems routinely. On that pre-
sol'ns mise, we suggest that each manu-
Vinblastine Velban IRI
Oncovin (R)
14 days at 2-10°
14 days at 2-10'' Reconstitute with special
facturer of a parenteral product to
Vincristine Sulfate
without significant diluting solution be reconstituted before use have on
loss of e;oteng_
Vitamin B Comelex Bejex IRI 2 weeks at room teme. the package insert or other suitable
Vitamin B Complex Solu B (R) Intended for immedi- Discard unused portions place a statement indicating the sta-
with Ascorbic Acid with C ate use
Vitamin B with c Folbesyn (R) Prepare immediately Essential to use all of di- bility after reconstitution and the
before use luent to reconstitute the
e!!wder
method of storing the reconstituted
Warfarin Sodium Coumodin Sodium Prepare immediately Haze and precipitate de· product. An excellent fonnat for this
before use; do not use velop slowly
after a few hours, use is Burroughs Wellcome's Anectine
only clear sol'n.
brochure, which also notes the loss
in potency per month at room and
refrigerator temperatures as well as
taste, form, or, occasionally, in the the first dose stat. We decided the the approximate duration of clinical
most accurate prescription would be potency at room temperatures. What-
case of infants, the physical volume
of the marketed dosage form. This made by reconstituting the sterile ever the fonnat, the infonnation
can be difficult if the drug needed power. Searching for stability aft- will be welcome and warmly ap-
is newly-marketed and available er reconstitution we got no help preciated by all concerned.
only in one or two dosage forms. from either brochure, catalog or
The problem can be illustrated package insert. REFERENCES
by a personal experience. A carbonic We started asking ourselves ques- 1. Barker, K.N., McConnell, W.E.: The Prob-
lems of Detecting Medication Errors in Hos-
anhydrase inhibitor was marketed tions when the order was received pitals. Am. J. Hosp. Pharm., 19:361, Aug.,
at 6 p.m. The questions we put to 1962.
in two dosage forms, tablets and 2. Barker, K.N.: Trends in Drug Distribu-
sterile powder for injection after company representatives (other than tion Systems. Am. J. Hosp. Phann., 19:595.
Dec., 1962.
reconstitution. A pediatrician pre- salesmen) took several days to an- 3. Blwnber~. M. : Packaging and Distribu-
tion of Hospttal Medications. Am. J. Hosp.
scribed a small dose for an infant- swer. Phann., 19:270. June, 1962.

October, 1963 79