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Trends in Manufacturing May 2025 PharmTech.com
COMPOUNDING
formats in labeling (Table I) that do not follow the
FDA format described above. For example, metopro-
lol tartrate (Lopressor) is an immediate-release beta
blocker that is dosed twice daily; metoprolol succi-
nate (Toprol XL) is an extended-release metoprolol
preparation formulated for once-daily dosage. Sec-
ondar y labeling on metoprolol succinate products
(37–39) references metoprolol tartrate to aid in tran-
sitioning patient dosage. Potassium phosphates injec-
tion (policy-exception drug) is labeled as phosphorus
mmol/mL and potassium mEq/mL on the primary
label and mg/mL amounts of potassium phosphate
monobasic and potassium phosphate dibasic equiva-
lent amounts of potassium and phosphate on the side
panel (40,41). Succinylcholine labeling may be incon-
sistent or different format (e.g., same concentration
products may be labeled as total drug mg/vial. (42–
44). These labels were likely approved before the salt
policy was implemented and have not been updated.
Summary
Par t one of t his series addresses pharmaceutica l
principles including terminology, regulations, and
dosage form labeling in compounded preparations.
Ty pes of dr ugs are identif ied. Non-salt (covalent)
drugs and salt (ionic) drugs are primary groups; cer-
tain salt drugs are further grouped as policy-excep-
tion salts. Policy-exception salts are dosed as non-salt
drugs including their molecule counterions; labeling
must identif y the equivalent active drug amounts.
Forms of drugs are also identified. Drug forms may
be solids or liquids; they may be bulk drugs or drugs
in mixtures; mixtures may include solutions, mix-
tures of solids, and commercial products (e.g., tab-
lets). Table II summarizes the drug types, dosage ra-
tionale, forms, active moiety identification, primary
labeling, and secondary labeling. The USP salt policy,
historical precedent, and identified exceptions are
the bases for these requirements; note significant la-
beling differences between salt drugs and policy-ex-
ception salts. Problems associated with the above are
identified. Effects resulting from misunderstanding
of drug salt principles may include overdosing or un-
derdosing of dosage form active moiety. Mislabeling
of dosage form content is also possible; attention to
detail is critical. Labeling may have variations for a
variety of reasons. Caref ul reading of commercial
product labeling with good understanding of prin-
ciples is mandatory for compounded product appli-
cations.
Acknowledgments
Comments from Alan M. Mancini, RPh, pharmaceutical
educator; Richard Poska, RPh, Flexo CMC Consulting;
Jan M. Keresztes, RPh, PharmD, pharmaceutical educa-
tor; and William R. Porter, PhD, pharmaceutical educa-
tor and principal scientist, Peak Process Performance
Partners, are greatly appreciated.
References
1. A n se l , H.C. Ph a r m aceut ic a l Ca lc u l at ion s, 1 4t h ed it ion.
Wolter s K luwer/ L ippi ncot t , Wi l l i a m s, & Wi l k i n s, Ph i l-
adelph ia, PA, 2013.
2. Tei xei ra, M.G. a nd Zat z, J.L . Phar maceut ical Calculat ions,
5t h edit ion. Joh n Wi ley & Sons, Hoboken NJ, 2017.
3. A l len , L .V., Jr. Phar maceut ical Compounding Calculat ion s
in T he A r t , Science, and Technology of Phar maceut ical Com-
p o un din g, 6t h e d . A me r ic a n Ph a r m a c i s t s A s s o c i a t ion ,
Wash i ng ton, D.C., 2020.
4. IC H . Q 9 (R 1) Q u a l i t y R i s k M a n a g e m e n t (IC H , Ja nu a r y
2023). ht t ps://d at aba se.ich.org/sites/defau lt/f i les/ ICH _
Q 9 % 2 8R 1% 29 _G u i d e l i ne _ St e p 4 _ 202 3 _ 01 26 _ 0.p d f (a c-
cessed Nov. 1, 202411-1-24).
5. ASHP. Compounding Frequent ly Asked Questions. ASHP.
or g. S e pte m b e r 2016. ht t ps:// w w w.a s hp.or g /-/me d i a/
a s s e t s/a d v o c a c y-i s s u e s/d o c s/c o m p o u n d i n g- g u i d a n c -
e s -f r e q u e n t l y-a s k e d- q u e s t i o n s . a s h x? l a= e n (a c c e s s e d
Nov.1, 2024).
6. FDA. Compounding and the FDA. Questions and Answers.
F DA . go v. Nov. 15 , 202 4. ht t ps:// w w w.fd a.gov/d r ugs/ hu-
m a n- d r u g- comp ou nd i n g /comp ou nd i n g-a nd-f d a- q ue s-
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7. P l u t a , P. L . C o m p o u n d i n g O v e r v i e w : P r i m a r y C o n s i d-
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o g y, 202 4 4 8 (2) p1 8-2 2 . ht t ps:// w w w.ph a r m t e c h .c om/
TABLE II. Drug dosage and labeling summary. 503A pharmacy labeling is also
regulated by state agencies.
Drug Type Description Drug Form
Active Moiety
Dosage
Primary Label Secondary label
Non-salt
(covalent)
Active moiety same
as (bulk drug)
Bulk drug or drug
mixture
Drug amount Drug amount Drug amount
Salt (ionic)
Active moiety is
drug-ion
Drug-ion amount Drug-ion amount
Drug-ion amount and
equivalent bulk drug
amount
Policy-exception
salt (ionic)
Active moiety
dosage is drug-ion +
drug counterion
Drug amount
Drug ion +
counterion amount
Drug amount and
equivalent drug-ion
amount
