Formulation and in vitro evalaution of solid dispersion tablets Containing dihydroarthemesinin

Abstract

Dihydroartemisinin (DHA) is a semi synthetic derivative of artemisinin antimalarial drug. The drug suffers from limited aqueous solubility, which hinders its bioavailability and clinical effectiveness. Hence, improved solubility is crucial for enhancing drug absorption and therapeutic efficacy. Solid dispersion is one of the promising approaches to enhance the solubility of poorly soluble drugs. Therefore, this study aimed to prepare a solid dispersion to enhance the solubility of DHA. Methods: In this study, PEG-4000, PEG-6000, and PVP K30 were utilized as the dispersion carriers to prepare solid dispersions by kneading and solvent evaporation methods. Drug polymer ratios of 1:1, 1:3, and 1:9 were investigated. FTIR spectroscopy was used to characterize drug-polymer interactions, while XRD, DSC, and SEM were used to characterized solid dispersions. Formulations were then evaluated for solubility and drug release. Results: Interaction study revealed there might not be drug-polymer interaction. Comparing the solid dispersion to the pure drug, XRD studies revealed a decrease in crystallinity. The SEM images of the solid dispersion particles, when compared to pure DHA, showed an amorphous morphology, as evidenced by their puffy appearance. Formulations with a 1:9 drug-to-PVP 30k ratio, prepared using the solvent evaporation method, exhibited the highest drug release, achieving 93.99% compared to 69.5% for the pure drug. The study on the flow properties of the solid dispersions demonstrated good flowability, with Carr's index ranging from 11.11±0.26 to 16.36±0.27, Hausner's ratio consistently below 1.25, and the angle of repose between 23.2±0.02 and 28.26±0.75. Tablets formulated from both physical mixtures and solid dispersions demonstrated good mechanical properties, with hardness values exceeding 4 kp. The tensile strength of these tablets also fell within the acceptable range, further confirming their structural integrity. Through systematic optimization, it was found that solid dispersions prepared via the solvent evaporation method, using a drug-to-polymer ratio of 1:9 with PVP as the polymer, yielded the most effective formulation. IV Conclusions: In general, solid dispersion of DHA utilizing the PVP30K, PEG-6000, and PEG 4000 were the best formulation to improve the solubility and in vitro release of the drug. Among the preparations of DHA solid dispersion, solid dispersion of DHA with PVP produces a formulation with optimal drug release. Recommendations: To advance solid dispersion technology, future research should focus on developing novel carriers, in vivo performance, stability study, and leveraging strategies to preserve product quality during scale up should be investigated. Interdisciplinary collaboration between academia, industry, and regulators is critical to translate research into clinically effective and commercially viable drug products.