Quality by Design Based Formulation and Development of a Novel Bi-Compound Pharmaceutical Capsule: An Innovative Approach for the Treatment of Hypertension

Abstract

Objectives: This study aimed to develop a novel bi-compound pharmaceutical capsule containing nifedipine gastro-retentive floating microspheres and telmisartan immediate-release solid dispersions using a Quality by Design (QbD) approach.Materials and Methods: QbD methodology was applied to optimize the formulations and ensure product quality. Risk assessment tools identified the Critical Material Attributes (CMA) and Critical Process Parameters (CPP). A Plackett-Burman screening design was applied to examine the impact of these factors on Critical Quality Attributes (CQA), followed by a Box-Behnken optimization design to establish the design space. The optimized formulation was analyzed, and drug-excipient compatibility was confirmed using FTIR, DSC, and XRD analyses. Results and Discussion: The results demonstrated that the optimized nifedipine microspheres remained buoyant for over 12 hr with 95.15% drug release at 12 hr. Telmisartan solid dispersions exhibited 97.83% drug release within 1 hr. Particle size analysis revealed the size range of 200-300 μm for bi-compound pharmaceutical formulation. The drug entrapment efficiency was 80-90% for both components. In vivo gamma scintigraphy in rats confirmed the gastro-retentive properties over 12 hr. Stability studies demonstrated <5% change in critical quality attributes over 12 months of storage, confirming the robustness of this formulation.Conclusion: The QbD-guided development of this bi-compound pharmaceutical capsule presents a promising approach for effective hypertension management, with the potential for improved patient compliance and therapeutic outcomes.

Keywords: Hypertension; Combination therapy; Quality by Design (QbD); Bi-compound pharmaceutical capsule; Gamma scintigraphy