Characterizing and Exploring the Differences in Dissolution and Stability Between Crystalline Solid Dispersion and Amorp
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Research Article Characterizing and Exploring the Differences in Dissolution and Stability Between Crystalline Solid Dispersion and Amorphous Solid Dispersion Xiaolin Wang,1 Lu Zhang,1 Danyang Ma,1 Xing Tang,1 Yu Zhang,1 Tian Yin,2 Jingxin Gou,1 Yanjiao Wang,1 and Haibing He1,3
Received 24 May 2020; accepted 25 August 2020 Abstract. Solid dispersion is one of the most effective ways to improve the dissolution of insoluble drugs. When the carrier can highly disperse the drug, it will increase the wettability of the drug and reduce the surface tension, thus improving the solubility, dissolution, and bioavailability. However, amorphous solid dispersions usually have low drug loading and poor stability. Therefore, the goal of this work is to study the increased dissolution and high stability of high drug-loading crystalline solid dispersion (CSD), and the difference in dissolution and stability of high-loading and low-loading amorphous solid dispersion (ASD). A CSD of nimodipine with a drug loading of 90% was prepared by wet milling, with hydroxypropyl cellulose (model: HPC-SL) and sodium dodecyl sulfate as stabilizers and spray drying. At the same time, the gradient drug–loaded ASD was prepared by hot melt extrusion with HPC-SL as the carrier. Each preparation was characterized by DSC, PXRD, FT-IR, SEM, and in vitro dissolution testing. The results indicated that the drug in CSD existed in a crystalline state. The amorphous drug molecules in the low drug-loading ASD were uniformly dispersed in the carrier, while the drug state in the high drug-loading ASD was aggregates of the amorphous drug. At the end of the dissolution assay, the 90% drugloading CSD increased cumulative dissolution to 60%, and the 10% drug-loading ASD achieved a cumulative dissolution rate of 90%. KEY WORDS: nimodipine (NMD); amorphous solid dispersion (ASD); crystalline solid dispersion (CSD); dissolution; stability.
INTRODUCTION The study and development of insoluble drugs is an unavoidable key issue in the pharmacological research field, and oral administration has become a major challenge faced by pharmacy researchers in the progression of new drugs (1,2). The solubility and dissolution rate of insoluble drugs delivered orally are the primary issues to be solved, particularly for the biopharmaceutics classification system II drug (BCSII drug) with low solubility and high permeability which include more than half of insoluble drugs. Solid dispersions are the preferred method to improve the dissolution and dissolution properties of poorly soluble drugs (2–4). The solid dispersion system is formed when drugs are evenly dispersed in a molecular, colloidal, or Xiaolin Wang and Lu Zhang contributed equally to this work. 1
Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Shenyang, 110016, China. 2 School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China. 3 To whom correspondence should be addressed. (e–mail: [email protected])
microcrystalline state, so that the solubility, dissolution
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