Palatability and Stability Studies to Optimize a Carvedilol Oral Liquid Formulation for Pediatric Use
Blanca Chiclana-Rodríguez1, Encarnacion Garcia-Montoya1,2, Miquel Romero-Obon1
1Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain.
Insights
Developing a palatable liquid formulation of carvedilol (CARV) is crucial for pediatric cardiovascular disease treatment. This study successfully created a stable, great-tasting CARV liquid, improving patient acceptance.
Area of Science:
- Pharmaceutical Sciences
- Pediatric Pharmacology
- Drug Formulation
Background:
- Carvedilol (CARV) is an alpha- and beta-blocker used off-label for pediatric cardiovascular conditions.
- A need exists for a pediatric-appropriate liquid formulation of CARV, as none are currently marketed.
- Palatability is critical for pediatric formulation acceptance, directly impacting adherence and therapeutic outcomes.
Purpose of the Study:
- To develop and assess the palatability and acceptability of novel CARV liquid formulations for pediatric use.
- To identify the optimal CARV formulation with enhanced taste and odor profiles.
- To evaluate the physicochemical and microbiological stability of the selected CARV formulation.
Main Methods:
- Preparation of CARV solutions with varying concentrations of flavoring agents and sweeteners (sucralose).
- In vivo taste assessment using adult volunteers to evaluate palatability and sensory attributes via questionnaires and sensory tests.
- Stability testing of the optimized formulation under various temperature conditions (25°C, 30°C, 40°C) for 6 months and in-use stability for 15 days at 25°C.
Main Results:
- Palatability scores significantly increased from 1.60 (unflavored) to 7.65 (optimized flavored formulation) on a 10-point scale.
- Bitterness was reduced from 66.67% to 17.86%, and taste pleasantness improved from 25/100 to 73/100 in the optimized formulation.
- The optimized CARV liquid formulation demonstrated confirmed physicochemical and microbiological stability over 6 months and during in-use conditions.
Conclusions:
- A palatable and stable liquid formulation of carvedilol suitable for pediatric use has been successfully developed.
- The optimized formulation incorporates pediatric-appropriate excipients, including sucralose and specific flavoring agents.
- This development addresses a critical unmet need for an acceptable and stable CARV oral solution in pediatric patients.
Abstract:
Carvedilol (CARV) is a blocker of α- and β- adrenergic receptors, used as an "off-label" treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.
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