Enalapril maleate has a solubility in water of 25mg per mL at room
temperature. It is a pro-drug which is converted to enalaprilat
following oral absorption. Enalaprilat (the injectable form) is
unsuitable for oral administration due to poor absorption.
Tablets
usually disperse readily in water (with crushing) and as the drug is
soluble small doses can then be measured.
Several formulations have
been studied.1,2,3 The first
study1 used a citrate buffer to improve
extraction efficiency and produce a clear filtered
solution. Subsequent studies have shown the drug to be stable
in a variety of other vehicles including a simple aqueous dispersion.2
Formula
A1
Enalapril Maleate 1mg per mL |
| |
| Enalapril
tablets 20mg |
5 |
|
| Citric acid
monohydrate |
0.35 |
g |
| Sodium citrate
dihydrate |
1 |
g |
| Parabens |
0.1 |
% |
| Water |
to 100 |
mL |
| |
| Expiry: 30
days. |
| |
| Storage: Refrigerate. |
| |
Notes
- The citrate buffer solution (pH 5) should be
made initially and then used to levigate the
crushed tablets. The mixture can then
be filtered (optional) using the buffer solution
to rinse the mortar and filter
medium. Add the parabens and make up
to volume with buffer.
- A 0.1mg per mL solution is also stable for
30 days.
- An expiry date of 7 days under refrigeration
is recommended for preservative free
preparations.
- Extraction of enalapril maleate from tablets
is not 100% efficient but this is unlikely to be
clinically significant. Extraction
efficiency is improved by sonication.
|
| | | | |
Formula
B2
Enalapril Maleate 1mg per mL |
| |
Nahata et al2 determined the
stability of enalapril maleate in deionised water,
citrate buffer solution (pH 5), or a 1:1 mixture
of Ora-Plus and Ora-Sweet.
Tablets were crushed
and mixed with the vehicle. Enalapril
was stable in the commercial base and citrate
buffer for 91 days at 4°C and 25°C.
In
deionised water the drug was stable for 56 days at
4°C.
No microbial testing was performed and a
more conservative expiry date is recommended for
these liquids. For example, the tablet
mixture in water would be expected to readily
support microbial growth especially at room
temperature during in-use
conditions. The addition of parabens to
the simple aqueous mixture could be considered as
this preservative is compatible with the
drug.1 |
| | | | |
Formula
C3
Enalapril Maleate 1mg per mL |
| |
| Enalapril
tablets 20mg |
6 |
|
| *Vehicle |
to 120 |
mL |
| |
*Choose from:
1:1
mixture of Ora-Sweet and Ora-Plus,
1:1 mixture
of Ora-Sweet SF and Ora-Plus, or
Cherry
syrup. |
| |
| Expiry: 30
days. |
| |
Stability:
Chemically stable for 60 days but
microbial testing
not performed. |
| |
Storage: Store in
amber, plastic bottles at 5°C or 25°C.
Protect
from light. |
| |
| Shake well
before use |
| | | | |
REFERENCES
- Boulton DW, Woods DJ, Fawcett JP, Tucker IG. The
stability of an enalapril maleate oral solution prepared from
tablets. Aust J Hosp Pharm 1994; 24: 151-6.
- Nahata MC, Morosco RS, Hipple TF. Stability of enalapril
maleate in three extemporaneously prepared oral
liquids. Am J Health-Syst Pharm 1998; 55:
1155-7.
- Allen LV, Erickson MA. Stability of alprazolam,
chloroquine phosphate, cisapride, enalapril maleate, and hydralazine
hydrochloride in extemporaneously compounded oral liquids.
Am J
Health-Syst Pharm 1998; 55: 1915-20.
|
