Department of pharmaceutical chemistry, Yashwantrao Bhonsle college of pharmacy, Sawant wadi, dist.- Sindhudurg.
Bempedoic acid, a key medication for lowering low-density lipoprotein cholesterol (LDL-C), is particularly useful for patients who are intolerant to statins or require additional LDL-C reduction. This study aims to evaluate the forced degradation behavior of Bempedoic acid under stress conditions using UV spectroscopy. The drug's stability was assessed in three tablet formulations: BEMPESTA (Torrent Pharmaceutical LTD, Tablet A), nexRed (Dr. Reddy’s Laboratory LMD, Tablet B), and CONSIVAS-BM (Emcure Pharmaceutical LTD, Tablet C), under various stress conditions, including acidic and basic hydrolysis, oxidation, and thermal exposure. UV absorbance measurements were taken at 258 nm using methanol as the solvent. The degradation results varied across formulations and stress conditions. Tablet A exhibited degradation of 78.02% in acidic, 85.01% in basic, 85.68% in oxidative, and 79.95% in thermal conditions. Under similar conditions, Tablet B showed 65.43%, 56.36%, 55.41%, and 61.59?gradation, respectively, while Tablet C exhibited 53.47%, 43.09%, 65.23%, and 21.76?gradation. This study provides key insights into Bempedoic acid degradation pathways, crucial for optimizing formulation and ensuring safety. The method is simple, time-efficient, and cost-effective, making it suitable for assessing Bempedoic Acid stress degradation, especially in smaller industries with limited access to advanced instruments.
Bempedoic acid (2,2,14,14-tetramethyl-8-hydroxypentadecanedioic acid) is an innovative small molecule that inhibits hepatic ATP-citrate lyase (ACL), a key enzyme in the cholesterol biosynthesis pathway[1] By inhibiting ACL, bempedoic acid enhances the clearance of low-density lipoprotein (LDL) particles, significantly reducing hypercholesterolemia, which is a major contributor to atherosclerosis and related cardiovascular diseases[2]. Cardiovascular disease remains the leading cause of death globally, underscoring the need for effective cholesterol-lowering therapies[3].
Figure. 1. Structure of Bempedoic Acid
Bempedoic acid's molecular formula is C??H??O?, with a molecular weight of 344.5, it is a white to off-white crystalline powder[4]. It belongs to BCS Class II, characterized by low solubility but high permeability. The compound is freely soluble at pH levels above 6 but becomes insoluble at pH 5 or below[5]. Its melting point is approximately 85°C, and it is sparingly soluble in methanol, requiring a buffer for maximum solubility[6]. Developed by Esperion Therapeutics Inc., bempedoic acid has been clinically proven to reduce LDL-cholesterol levels and was approved by the U.S. Food and Drug Administration (FDA) in 2020 for the treatment of hypercholesterolemia in adults requiring additional LDL-cholesterol lowering. The European Medicines Agency (EMA) also recommended it for the treatment of primary hypercholesterolemia and mixed dyslipidemia. Despite its efficacy in cholesterol reduction, ongoing trials are still assessing its long-term potential in preventing cardiovascular events[7]. Forced degradation studies are essential for understanding the stability of pharmaceutical formulations. These studies simulate extreme conditions to evaluate the chemical and physical stability of drug substances. This research aims to conduct a comprehensive forced degradation study of bempedoic acid tablets from different brands[8]. By comparing the degradation profiles under various stress conditions—such as heat, light, humidity, and oxidation—this study will provide crucial insights into the stability, efficacy, and quality of bempedoic acid tablets across different formulations. The findings will contribute to better regulatory understanding and help ensure consistent therapeutic outcomes for patients[9].
MATERIALS AND METHODS
Instruments
The analysis was carried out using a UV-Visible Spectrophotometer (SHIMADZU, model No. UV-1900), equipped with a pair of 1.0 cm path-length quartz cuvettes. The instrument had a wavelength range of 190 to 1100 nm, with a 20W halogen lamp and a deuterium lamp as light sources.
Chemicals And Reagents
Chemicals and reagents used in the study included methanol (analytical grade), distilled water, 0.1 N hydrochloric acid (HCl), 0.1 N sodium hydroxide (NaOH), and 0.1 N hydrogen peroxide (H?O?). These reagents were chosen to induce degradation under various stress conditions, such as acidic, basic, and oxidative environments. The forced degradation study of bempedoic acid tablets was conducted using three different brands of tablets: Bempesta (Torrent Pharmaceuticals Ltd, Gujarat), NexRed (Dr. Reddy's Laboratories Ltd), and CONSIVAS-BM (Emcure Pharmaceuticals Ltd, Pune).
Preparation Of Standard Stock Solution:
To prepare a 10 µg/mL stock solution of bempedoic acid, 5 mg of the API was weighed and dissolved in 50 mL of methanol in a 100 mL volumetric flask. The mixture was swirled gently and sonicated for 15 minutes. After cooling, 1 ml prepared solution was adjusted to 10 mL with methanol, resulting in a 10 µg/mL solution.
Preparation Of Simple Solution Tab A, B, C
To prepare the sample solution of bempedoic acid from Tablets A, B, and C, the tablets were weighed and subsequently fractured. For Tablet A, a finely powdered drug weighing 5 mg was accurately added to 50 ml of methanol to create a 100 µg/mL solution, which was then sonicated for 15-20 minutes at room temperature and filtered using Whatman filter paper (No. 41). The filtered 100 microgram concentration solution was diluted into five different dilutions. Specifically, for Tablet A, 1 ml of the 100 µg/mL solution was pipetted into a 10 ml volumetric flask and filled to the mark with pure methanol to create a 10 µg/mL solution. Similar procedures were followed for the remaining dilutions (4, 6, 8, and 10 micrograms) by taking 0.4 ml, 0.6 ml, 0.8 ml, 1 ml from the 100 µg/mL solution, respectively. The same initial steps were applied to Tablet B, where 5 mg of finely powdered drug was also added to 50 ml of methanol to make a 100 µg/mL solution, sonicated, filtered, and diluted in the same manner. For Tablet C, however, the dilution involved a methanol and distilled water mixture in a 75:25 ratio. The process for preparing the subsequent dilutions for Tablet C remained consistent with that of Tablets A and B. Finally, the wavelength and absorbance of all sample solutions were checked using a UV spectrophotometer.
Degradation Studies:
An equivalent volume of the bempedoic acid solution was placed in a beaker, and 0.1 N NaOH was added. The resulting alkaline solution was transferred into cuvettes for spectrophotometric analysis, where the absorbance of the samples was measured at a wavelength of 258 nm[10] . Degradation With Hydrogen Peroxide (H?O?):
An equal volume of the bempedoic acid solution was prepared in a beaker and combined with 0.1 N H?O?. This solution was then placed into cuvettes, and the total absorbance was assessed at 258 nm to evaluate the degradation effect of hydrogen peroxide[11]
An equal volume of bempedoic acid solution was contained in a beaker and gradually heated for a duration of 10 minutes. After heating, the solution was transferred to cuvettes, and absorbance readings were recorded at 258 nm to analyze the impact of heat on the stability of the compound[12]
An equivalent volume of the bempedoic acid solution was placed in a beaker, and 0.1 N HCl was introduced. The resulting acidic solution was then placed in cuvettes for analysis, with absorbance measurements taken at 258 nm to observe the effects of hydrochloric acid on degradation[12,13] RESULT AND DISCUSSION
The absorbance spectrum of the standard solution of bempedoic acid showed a peak at 258 nm, confirming this wavelength as its lambda max. This finding is essential for quantitative analysis of bempedoic acid in various formulations, aligning with previously reported absorbance characteristics[14].
Figure.2. UV Spectrum of Bempedoic Acid
The calibration curve for bempedoic acid in methanol demonstrated linearity within the concentration range of 4-10 ?g/ml. The absorbance values obtained for all prepared concentrations were plotted, showing a direct relationship between concentration and absorbance. The linear regression analysis yielded a standard equation of y=0.0425x?0.1005, with a high regression coefficient of 0.9987, indicating an excellent correlation. This strong linearity confirms the method's reliability for quantifying bempedoic acid in solution[14,15].
Figure. 3. Calibration Curve of Std Bempedoic Acid
The degradation studies for Tablets A, B, and C revealed significant differences in stability under various conditions, as summarized in the results. In acidic conditions (HCl), Tablet A retained 78.02% of its active ingredient, while Tablet B and Tablet C showed lower retention at 65.43% and 53.47%, respectively. In basic conditions (NaOH), Tablet A exhibited good stability with 85.01% retention, whereas Tablet B and Tablet C were notably less stable, retaining only 56.36% and 43.09%. Under oxidative conditions (H?O?), Tablet A maintained a high retention of 85.68%, while Tablet B and Tablet C showed more significant degradation at 55.41% and 65.23% retention, respectively. In terms of heat stability, Tablet A retained 79.95%, contrasting sharply with Tablet C, which retained only 21.76%. Overall, Tablet A consistently demonstrated the highest stability across all conditions, while Tablet C exhibited substantial degradation, particularly under heat and acidic environments. These findings highlight the necessity for formulation adjustments to enhance the stability of Tablets B and C, ensuring quality throughout their shelf life[13].
Figure.4. Degradation Profile of Bempedoic Acid tab A, B & C
CONCLUSION
The degradation studies of Tablets A, B, and C highlighted significant differences in their stability under various environmental conditions, including acidic, basic, oxidative, and thermal conditions. Tablet A consistently demonstrated superior stability, with the highest retention of the active ingredient across all tested scenarios. In contrast, Tablet C exhibited substantial degradation, particularly under acidic and heat conditions, indicating a critical need for formulation modifications to improve its stability. Tablet B, while exhibiting moderate stability, also requires adjustments to ensure its effectiveness over time. Overall, these findings emphasize the importance of stability testing in the formulation development of pharmaceutical products to guarantee quality and efficacy throughout their shelf life.
ACKNOWLEDGEMENT
Authors are thankful to principal of Yashwantrao Bhonsale Collage of Pharmacy, Sawantwadi for providing experimental facilities.
REFERENCES
Vinod Biradar*, Yash Patil, Harshada Maral, Chinmay Pingulkar, Sanika Rane, Om Atak, Vijay Jagtap, Evaluation of Forced Degradation Behavior of Bempedoic Acid in Different Indian Branded Tablet Formulations, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 01, 102-107. https://doi.org/10.5281/zenodo.14586337
10.5281/zenodo.14586337
