Development and Characterization of Different Dosage Forms of Nifedipine/Indomethacin Fixed-Dose Combinations
Abdulmajeed A Althobaiti1, Eman A Ashour1, Ahmed Almotairy1,2
1Department of Pharmaceutics and Drug Delivery, University of Mississippi, School of Pharmacy, MS 38677.
Insights
This study developed novel fixed-dose combination (FDC) dosage forms for rheumatoid arthritis (RA) and cardiovascular disease (CVD) risk management. The new formulations improved drug release profiles and stability, enhancing patient compliance.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Materials Science
Background:
- Rheumatoid arthritis (RA) affects 1.3 million in the US, with significant cardiovascular disease (CVD) risks, including hypertension.
- Current RA treatments may involve polypharmacy, potentially impacting patient compliance and quality of life.
Purpose of the Study:
- To design and develop novel fixed-dose combination (FDC) dosage forms of nifedipine and indomethacin.
- To achieve distinct release profiles: immediate for nifedipine and delayed-extended for indomethacin.
- To enhance drug solubility and stability using advanced manufacturing techniques.
Main Methods:
- Utilized hot-melt extrusion (HME) and fused deposition modeling (FDM) for fabricating capsule-in-capsule and 3D printed tablet dosage forms.
- Characterized drug release profiles at different pH levels (1.2 and 6.8).
- Assessed drug content, physical stability (differential scanning calorimetry, thermal analysis), and chemical stability.
Main Results:
- Nifedipine release significantly improved to 94% within 30 minutes, compared to 2% for pure nifedipine.
- Indomethacin release was successfully delayed at pH 1.2 and extended at pH 6.8.
- All formulations exhibited excellent drug content (95-98%), complete drug solubilization in polymeric carriers, and stability without recrystallization or degradation.
Conclusions:
- Successfully developed stable and effective nifedipine/indomethacin FDC dosage forms with tailored release profiles.
- The developed formulations demonstrate potential to improve patient compliance and reduce polypharmacy in managing RA and associated CVD risks.
- Advanced techniques like HME and 3D printing offer promising avenues for creating advanced drug delivery systems.
Abstract:
Studies have shown that 40 individuals out of 100,000 are diagnosed with rheumatoid arthritis (RA) yearly, with a total of 1.3 million in the United States. Furthermore, the impact of RA in some cases can extend to cardiovascular diseases (CVD), as the studies showed that 84% of RA patients are at risk of developing hypertension. This study aims to design and develop different dosage forms (capsule-in-capsule and three-dimensional (3D) printed tablet) of nifedipine/indomethacin fixed-dose combination (FDC). The hot-melt extrusion (HME) was utilized alone and with fused deposition modeling (FDM) techniques The developed dosage forms were intended to provide delayed-extended and immediate release profiles for indomethacin and nifedipine, respectively. FDC dosage forms were successfully developed and characterized. Nifedipine formulations showed significant improvement in release profiles, having 94% of the drug release at 30 minutes compared with pure nifedipine, which had a percent release of 2%. Furthermore, the release of indomethacin was successfully delayed at a pH of 1.2 and extended at a pH of 6.8. Differential scanning calorimetry results showed endothermic crystalline peaks at 165 °C and 176 °C for indomethacin and nifedipine, respectively. Moreover, the thermal analysis of all formulations showed the absence of the endothermic peaks indicating complete solubilization of indomethacin and nifedipine in the polymeric carriers. All formulations had post-processing drug content in the range of 95% to 98%. Moreover, results from the stability study showed that all formulations were able to remain chemically and physically stable with no signs of recrystallization or degradation. The designed FDC dosage forms could improve the quality of life by enhancing patient compliance and preventing the need for polypharmacy.
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