The development and stability assessment of extemporaneous pediatric formulations of Accupril

Quinapril, the active ingredient in Accupril ® tablets, is an ACE inhibitor used to treat hypertension. Quinapril is unstable in aqueous solution and therefore the development of a liquid formulation is a significant challenge. Previous studies show the rate of degradation of quinapril into its two...

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Bibliographic Details
Published in:International journal of pharmaceutics 2005-11, Vol.304 (1), p.135-144
Main Authors: Freed, Anita L., Silbering, Steven B., Kolodsick, Kevin J., Rossi, David T., Mahjour, Majid, Kingsmill, Carol A.
Format: Article
Language:English
Subjects:
Accupril
Biological and medical sciences
Buffers
Child
Drug Compounding
Drug Design
Drug Labeling
Drug Stability
Excipients
Excipients - chemistry
Extemporaneous formulation
General pharmacology
Humans
Hydrogen-Ion Concentration
Medical sciences
Molecular Structure
Pediatric
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Quinapril hydrochloride
Solutions
Stability
Tetrahydroisoquinolines - chemistry
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Summary:Quinapril, the active ingredient in Accupril ® tablets, is an ACE inhibitor used to treat hypertension. Quinapril is unstable in aqueous solution and therefore the development of a liquid formulation is a significant challenge. Previous studies show the rate of degradation of quinapril into its two major degradants to be pH dependent, indicating the parent compound to be most stable in the narrow pH range of 5.5–6.5. Accupril (20 mg) and readily available pharmaceutical components were combined to generate three formulations that are stable for at least 28 days, possess acceptable appearance, and are palatable to pediatric patients. To combat the presence of magnesium carbonate in the Accupril tablets, which increase the pH of the solution above 6.5, several pharmaceutically available buffers were incorporated. Nine prototypes were developed and their characteristics evaluated after 1 week under stressed conditions. The three that most closely matched the stability criteria were chosen for a definitive stability study. A stability-indicating method was developed and validated for these studies. All three formulations met the following specifications when stored at 5 °C for 6 weeks; Quinapril remained ≥90% intact and the two known degradants did not reach values ≥3.0% individually or ≥5.0% combined.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2005.08.007