The use of partially hydrolysed polyvinyl alcohol for the production of high drug-loaded sustained release pellets via extrusion-spheronisation and coating: In vitro and in vivo evaluation

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• 作者：G. Verstraete^a ; ¹ ; W. De Jaeghere^a ; ¹ ; J. Vercruysse^a ; W. Grymonpré ; ^a ; V. Vanhoorne^a ; F. Stauffer^b ; T. De Beer^b ; A. Bezuijen^c ; J.P. Remon^a ; C. Vervaet^a ; ^{Chris.Vervaet@Ugent.be}
• 关键词：Extrusion-spheronisation ; Pelletisation aid ; Polyvinyl alcohol ; High drug load ; Pellets ; Sustained release
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：30 January 2017
• 年：2017
• 卷：517
• 期：1-2
• 页码：88-95
• 全文大小：1179 K
• 卷排序：517

文摘

Partially hydrolysed polyvinyl alcohol (PVA) was evaluated as a pelletisation aid for the production of pellets with a high acetaminophen and metformin hydrochloride concentration (>70%, w/w). Mixtures with varying drug concentration and PVA/microcrystalline cellulose (MCC) ratios were processed via extrusion-spheronisation, either after addition of PVA as a dry powder or as an aqueous solution. Finally, high drug- loaded metformin pellets were coated with a methacrylic acid copolymer (Eudragit™ NM 30D) and evaluated for their sustained release potency in vitro and in vivo. The plasticity index of the wet mass increased by the addition of PVA to the formulation, which resulted in enhanced extrusion-spheronisation properties, even at a high drug load. Although the MCC concentration was successfully lowered by adding PVA, the inclusion of MCC in the formulation was essential to overcome problems related to the tackiness effect of PVA during extrusion. Overall, wet addition of PVA was superior to dry addition, as pellets with a higher mechanical strength and narrower particle size distribution were obtained. Pellets containing 87% (w/w) metformin hydrochloride were successfully layered with 20% (w/w) coating material, yielding sustained release pellets with a final drug load of 70% (w/w). In addition, the sustained release characteristics of the PVA-based pellets with a high drug content were confirmed in vivo as no difference with the Glucophage™ SR reference formulation was observed.