Formulation in Pharmacy Practice  - eMixt

Enalapril
 
 
Properties
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.

Compounding alternatives
Tablets usually disperse readily in water (with crushing) and as the drug is soluble small doses can then be measured.

Formulations
A New Zealand standardised formulation is available Formula and Batch Sheet
This formula uses Ora-Blend/SF or Ora-Plus and Ora-Sweet/SF; 1:1

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
Citric acid monohydrate 0.35  g
Sodium citrate dihydrate g
Parabens 0.1  %
Water to   100  mL
Expiry:  30 days.
Storage:  Refrigerate.
Notes
  1. 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.
  2. A 0.1mg per mL solution is also stable for 30 days.
  3. An expiry date of 7 days under refrigeration is recommended for preservative free preparations.
  4. 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 4C and 25C.
In deionised water the drug was stable for 56 days at 4C.
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  
*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 5C or 25C.
Protect from light.
Shake well before use

 
References
  1. 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.
  2. 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.
  3. 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.
 
Formulation in Pharmacy Practice
Page updated June 2014