Related Experiment Video
Updated: May 9, 2026
11:27
A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms.
Talita A Cunha1, Raphael C Serpa, Ana Paula M de Oliveira
1Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil.
AAPS Pharmscitech
|July 31, 2013
Summary
Stearic acid (SA) enhances enalapril maleate (EM) stability in solid dosage forms by reducing degradation products. This offers a superior alternative to enalapril sodium salt (NaE) formulations for improved drug stability.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Materials Science
Background:
- Enalapril maleate (EM) exhibits instability with excipients, leading to degradation products like enalaprilate and diketopiperazine (DPK).
- In situ enalapril sodium salt (NaE) preparation improves stability but can cause issues like gas release if the reaction is incomplete.
- Developing stable enalapril formulations is crucial for effective hypertension treatment.
Purpose of the Study:
- To evaluate the impact of stearic acid (SA) on enalapril stability within microcrystalline cellulose (MCC) pellets.
- To compare the stability of enalapril maleate (EM) and enalapril sodium salt (NaE) in the presence and absence of SA.
- To assess the potential of SA as a stabilizing agent in enalapril solid dosage forms.
Main Methods:
- Preparation of MCC pellets containing EM or NaE, with and without SA, using extrusion-spheronization.
- Characterization of the prepared pellets.
- Evaluation of enalapril stability, degradation product formation (DPK, enalaprilate), and dissolution profiles.
- Thermal analysis of SA-NaE binary mixtures to investigate interactions.
Main Results:
- Stearic acid (SA) significantly reduced enalaprilate and diketopiperazine (DPK) formation in enalapril maleate (EM) pellets.
- Overall enalapril degradation was lower in SA-containing pellets compared to those without SA or with enalapril sodium salt (NaE) alone.
- Formulations with 5% crospovidone maintained immediate-release characteristics.
- Unexpected enalapril degradation occurred in NaE pellets with SA, indicating a detrimental interaction.
Conclusions:
- Stearic acid (SA) incorporation into enalapril maleate (EM) formulations enhances drug stability in solid dosage forms.
- SA-containing formulations present a viable alternative to enalapril sodium salt (NaE) preparation for improved enalapril stability.
- The observed stabilization effect of SA may extend to other angiotensin converting enzyme inhibitors with similar degradation pathways.
Related Concept Videos
01:20Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
01:22Factors Influencing Drug Absorption: Physicochemical Parameters
The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
01:21Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles in drug...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles in drug...
01:23Factors Affecting Dissolution: Particle Size and Effective Surface Area
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are employed to...