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通过结晶共附聚技术制备用于直接压片的萘普生-崩解剂附聚物的颗粒设计

Particle design of naproxen-disintegrant agglomerates for direct compression by a crystallo-co-agglomeration technique.

作者信息

Maghsoodi Maryam, Taghizadeh Omid, Martin Gary P, Nokhodchi Ali

机构信息

School of Pharmacy and Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran.

出版信息

Int J Pharm. 2008 Mar 3;351(1-2):45-54. doi: 10.1016/j.ijpharm.2007.09.033. Epub 2007 Sep 29.

Abstract

The purpose of the present research was to obtain directly compactible agglomerates of naproxen containing disintegrant by a novel crystallo-co-agglomeration (CCA) technique. Acetone-water containing hydroxypropylcellulose (HPC) was used as the crystallization medium. Acetone acted as a good solvent for naproxen as well as a bridging liquid for agglomeration of crystallized drug with disintegrant and aqueous phase as non-solvent. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and scanning electron microscopy. The agglomerates were compressed at different compression pressures and dissolution studies were carried out for the tablets produced at lowest compression force. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to the fragmentation which occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and disintegrant did not undergo structural modifications. The dissolution rate of naproxen from the agglomerates could be controlled by the amount of included disintegrant, being enhanced as the latter was increased. Moreover, the results showed that when the disintegrants were included both intragranularly and extragranularly during agglomeration of naproxen particles, tablets containing these agglomerates dissolved at a faster rate than the tablets containing crystallized naproxen with the same amount of disintegrant incorporated only extragranularly by physical mixing. In conclusion, the properties of agglomerated crystals, such as flowability, compactibility and dissolution rate were improved profoundly using the developed technique resulting in successful direct tableting without need to additional process of physical blending of agglomerates and disintegrants.

摘要

本研究的目的是通过一种新型的结晶共附聚(CCA)技术直接获得含崩解剂的萘普生可压性附聚物。含有羟丙基纤维素(HPC)的丙酮 - 水用作结晶介质。丙酮既是萘普生的良好溶剂,又是结晶药物与崩解剂附聚的桥连液体,水相作为非溶剂。通过差示扫描量热法(DSC)、粉末X射线衍射(XRPD)和扫描电子显微镜对附聚物进行表征。在不同的压缩压力下对附聚物进行压片,并对以最低压力生产的片剂进行溶出度研究。附聚物的粒径增长和球形形状导致形成具有良好流动性和堆积性能的产品。附聚晶体压实性能的改善归因于压缩过程中发生的破碎。DSC和XRPD研究表明,在HPC和崩解剂存在下结晶的萘普生颗粒未发生结构改性。萘普生从附聚物中的溶出速率可通过所含崩解剂的量来控制,随着崩解剂含量的增加而加快。此外,结果表明,当在萘普生颗粒附聚过程中同时在颗粒内和颗粒外加入崩解剂时,含有这些附聚物的片剂比含有相同量崩解剂仅通过物理混合在颗粒外加料的结晶萘普生片剂溶解速度更快。总之,使用所开发的技术可显著改善附聚晶体的性能,如流动性、可压性和溶出速率,从而成功实现直接压片,无需对附聚物和崩解剂进行额外的物理混合过程。

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