通过表面改性克服药物晶体的可压性差。
Overcoming poor tabletability of pharmaceutical crystals by surface modification.
机构信息
Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 9-127B Weaver-Densford Hall, 308 Harvard Street S.E., Minneapolis, Minnesota 55455, USA.
出版信息
Pharm Res. 2011 Dec;28(12):3248-55. doi: 10.1007/s11095-011-0518-2. Epub 2011 Jun 28.
PURPOSE
To test the hypothesis that coating particles with a highly bonding polymer is effective in improving tabletability of poorly compressible drugs.
METHODS
Micronized acetaminophen (d (90) < 10 μm, Form I) was coated with 1%-10% (wt%) hydroxypropyl cellulose (HPC) by spray-drying. Phase nature of acetaminophen powders was identified using powder X-ray diffractometry, SEM, and thermal analysis. Powder tabletability was evaluated on a compaction simulator. Mechanical properties of acetaminophen and HPC were determined by nanoindentation.
RESULTS
Spray-drying successfully produced acetaminophen particles enveloped with a layer of HPC but did not cause any detectable phase change of acetaminophen. At 200 MPa, physical mixtures containing up to 40% HPC could not be compressed into intact tablets. In contrast, acetaminophen coated with 1% to 10% HPC could form strong tablets (tensile strength was 1.9-7.0 MPa) at 200 MPa. Under a given compaction pressure, tablet tensile strength increased sharply with the amount of HPC coating. The profoundly improved tabletability of acetaminophen confirmed the effectiveness of the particle coating approach in improving tableting performance of drugs.
CONCLUSIONS
HPC coating by spray-drying profoundly enhances tabletability of acetaminophen. This strategy is expected to have transformative effects on formulation development of poorly compressible drugs.
目的
验证以下假设，即将高键合聚合物涂覆在颗粒表面可有效改善难压缩药物的可压性。
方法
采用喷雾干燥法，用 1%-10%（重量%）羟丙基纤维素（HPC）对粒径小于 10μm（d（90））的微粉化对乙酰氨基酚（I 型）进行包衣。采用粉末 X 射线衍射法、SEM 和热分析鉴定对乙酰氨基酚粉末的相性质。在压片机上评估粉末的可压性。采用纳米压痕法测定对乙酰氨基酚和 HPC 的力学性能。
结果
喷雾干燥成功地生产出了被 HPC 层包裹的对乙酰氨基酚颗粒，但未引起对乙酰氨基酚的任何可检测到的相变化。在 200MPa 下，含高达 40%HPC 的物理混合物无法压制成完整的片剂。相比之下，用 1%-10%HPC 包衣的对乙酰氨基酚可在 200MPa 下形成强片剂（拉伸强度为 1.9-7.0MPa）。在给定的压缩压力下，片剂的拉伸强度随 HPC 包衣量的增加而急剧增加。对乙酰氨基酚可压性的显著改善证实了颗粒包衣方法在改善难压制药剂压片性能方面的有效性。
结论
喷雾干燥用 HPC 包衣可显著提高对乙酰氨基酚的可压性。该策略有望对难压缩药物的制剂开发产生变革性影响。
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