The impact of hot-melt extrusion on the tableting behaviour of polyvinyl alcohol

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• 作者：W. Grymonpré ; ^a ; ¹ ; W. De Jaeghere^a ; ¹ ; E. Peeters^b ; P. Adriaensens^c ; J.P. Remon^a ; C. Vervaet^a ; ^{Chris.Vervaet@UGent.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hot-melt extrusion ; Tableting ; Elastic recovery ; Polyvinyl alcohol ; Oral drug delivery ; Immediate release
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：10 February 2016
• 年：2016
• 卷：498
• 期：1-2
• 页码：254-262
• 全文大小：1691 K

文摘

There is evidence that processing techniques like hot-melt extrusion (HME) could alter the mechanical properties of pharmaceuticals, which may impede further processability (e.g. tableting). The purpose of this study was to evaluate if HME has an impact on the tableting behaviour of polyvinyl alcohol (PVA)-formulations. Mixtures of partially hydrolysed PVA grades (with a hydroxylation degree of 75 and 88%) and sorbitol (0, 10 and 40%) were extruded, (cryo-) milled and compressed into compacts of 350 ± 10 mg. Before compression all intermediate products were characterized for their solid-state (T_g, T_m, crystallinity) and material properties (particle size, moisture content, moisture sorption). Because both PVA-grades required higher extrusion temperatures (i.e. 180 °C), sorbitol was added to PVA as plasticizing agent to allow extrusion at 140 °C. Compaction experiments were performed on both physical mixtures and cryo-milled extrudates of PVA-sorbitol. By measuring tablet tensile strength and porosity in function of compaction pressure, tableting behaviour was compared before and after HME by means of the CTC-profiles (compressibility, tabletability, compactibility). A higher amorphous content in the formulation (as a result of HME) negatively influenced the tableting behaviour (i.e. lower tablet tensile strength). HME altered the mechanical properties towards more elastically deforming materials, thereby increasing tablet elastic recovery during decompression. The lower tensile strengths resulted from a combined effect of less interparticulate bonding areas (because of higher elastic recovery) and weaker bonding strengths per unit bonding area (between glassy particles).