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CONTINUING PROFESSIONAL DEVELOPMENT
SOLUTIONS THROUGH COMPOUNDING
many advantages over other routes
of administration including bypassing
first-pass metabolism, limiting systemic
side effects, and decreasing potential
drug-drug interactions. In addition, the
reported ease of use has resulted in
improved patient adherence.
there have been many animal studies
investigating the topical application
is limited to two small retrospective
In the first study, topical
gabapentin led to a ≥50% reduction in
pain, within eight weeks in 28 (80%) of
35 patients with vulvodynia.9 The second
study showed that 20 of 23 patients
with severe chronic pain benefited from
topical gabapentin, with a reduction
in the mean ± SD pain scores from
8.2 ± 1.4 to 5.6 ± 1.7 after one month,
and 11 patients achieving a clinically
meaningful 30% reduction in pain.
All patients who responded to topical
gabapentin treatment experienced pain
relief within one hour of application.
Gabapentin compounded for topical
application may meet specific patient
needs as a useful adjunct or alternative
for the treatment of neuropathic pain.
Active pharmaceutical ingredient
Gabapentin (C9H17NO2, MW 171.2), a
white to off-white, crystalline solid is
freely soluble in water and in alkaline
and acidic solutions. A 2% solution in
water has a pH of 6.5 to 8.0.
gabapentin is available as a capsule
or tablet, the API/raw material should
be used to compound topical dosage
forms to avoid any potential interaction
between the tablet or capsule excipients
and the topical base.
Gabapentin, which can exist in
three polymorphic forms in addition
to the monohydrate, is available
commercially as Form II (α-gabapentin).
Interconversion between the
polymorphic forms has been reported to
occur in the solid-state, due to increased
temperature and on milling.
Degradation of gabapentin by an
intramolecular cyclisation results in the
formation of the lactam (see Figure 1).
This degradation can occur in the
solid-state, due to both the presence of
excipients and various manufacturing
processes. It is therefore important from
a quality perspective to both minimise
and monitor lactamisation. Due to the
increased toxicity of gabapentin lactam,
the US Pharmacopoeia (USP) limit on the
lactam is less than 0.4%.
Figure 1. Chemical structure of gabapentin,
showing degradation by lactamisation
The pharmacist, in consultation with
the prescriber, may decide on the use
of an appropriate topical base to meet
the requirements of the patient. Various
bases available, including Pluronic Lecithin
Organogel (PLO) and Lipoderm have
been previously described.
base contains a proprietary liposomal
component, which increases the skin
penetration of a variety of drugs. It has
been evaluated for allergic reactions,
with no adverse reactions reported
after an extensive 2-month study.
Lipoderm base is also available as Lipoderm
ActiveMax for preparations containing
high salt loads; Anhydrous Lipoderm
for APIs that are unstable in water; and
Lipoderm High Molecular Weight for high
molecular weight APIs.
Formulation considerations and
The use of shear mixing when
incorporating gabapentin into Lipoderm
is important, since it results in the
formation of the micelles (bilayers,
liposomes) that incorporate the drug
and enhance its skin penetration,
in addition to ensuring content
13 Shear mixing is possible
through use of a mortar and pestle, or
an electronic mortar and pestle (EMP)
as shown in Figure 2. The EMP is an
efficient tool and its versatility extends
to compounding ointments, creams,
gels and suspensions.
WHY use the EMP?
Homogeneous mixture – quality
Ease of use/versatility
Individual jars/closed system – low
risk of contamination
Time and cost effective
Jar can be used both to prepare
the product and to dispense final
Figure 2. Electronic mortar and pestle (EMP) and
the advantages for its use in compounding15
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