Levina M, Rubinstein M H
School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom.
J Pharm Sci. 2000 Jun;89(6):705-23. doi: 10.1002/(SICI)1520-6017(200006)89:6<705::AID-JPS2>3.0.CO;2-D.
An ultrasonic (US) compaction rig has been developed that is capable of providing compaction pressure together with high-power ultrasonic vibrations of 20 kHz to a powder or granular material in a die. The rig has been used to investigate the effect of US on the compaction properties of paracetamol, a drug that produces tablets that are weak and frequently exhibit capping. It was found that coherent paracetamol tablets could be prepared by US-assisted compaction at pressures as low as 20 to 30 MPa. Application of US before and after compaction was not found to be as effective as US applied during compaction. The breaking forces of the tablets produced with US applied during compaction were found to be consistently significantly higher than when compaction was performed conventionally or with US applied before or after compaction. The application of US during compaction made it possible to increase tablet breaking force, typically by a factor of 2 to 5. It was concluded that pressure should be applied together with US to achieve a better acoustical contact, which is required to transmit vibrations from the horn to the material and also to bond the surfaces of the particles. US application during compaction also resulted in an increase in apparent density, in relation to the apparent density of conventionally prepared paracetamol tablets, of up to 12.8%. US appears to improve particle rearrangement and provide energy for partial melting of particle asperities and subsequent fusion of particle surfaces, thus increasing interparticulate bonding. Development of solid bridges between the particles during US-assisted compaction was observed on scanning electron photomicrographs. Solid bridge formation was thought to result in a reduction of void space, which in turn reduced the rate of water penetration into the compacts and consequently increased tablet disintegration and drug dissolution times. It was found that the results of US-assisted compaction are influenced by formulation and US time. An increase in binder (polyvinylpyrrolidone) concentration and/or US time resulted in a significant increase in the breaking forces of paracetamol tablets produced with US. When paracetamol was mixed with a second material, such as dicalcium phosphate dihydrate and microcrystalline cellulose, stronger compacts were prepared by US-assisted compaction compared with the tablets containing no filler. Positive interactions were considered to have occurred as a result of US-induced bonding between the two materials. Overall, the application of US was found to significantly improve the compaction properties of paracetamol.
已研发出一种超声波（US）压实装置，该装置能够在模具中对粉末或颗粒材料施加压实压力，并同时施加20 kHz的高功率超声波振动。该装置已用于研究超声波对扑热息痛压实特性的影响，扑热息痛制成的片剂强度较弱，且经常出现裂片现象。研究发现，通过超声波辅助压实，在低至20至30 MPa的压力下即可制备出粘结性良好的扑热息痛片剂。结果表明，压实前和压实后施加超声波的效果不如压实过程中施加超声波的效果好。研究发现，压实过程中施加超声波所制得片剂的断裂力始终显著高于传统压实方式或压实前后施加超声波所制得片剂的断裂力。压实过程中施加超声波能够使片剂断裂力提高，通常提高2至5倍。得出的结论是，应在施加超声波的同时施加压力，以实现更好的声学接触，这对于将振动从变幅杆传递到材料以及粘结颗粒表面都是必需的。与传统制备的扑热息痛片剂的表观密度相比，压实过程中施加超声波还使表观密度提高了高达12.8%。超声波似乎改善了颗粒重排，并为颗粒粗糙表面的部分熔化以及随后颗粒表面的融合提供了能量，从而增加了颗粒间的粘结。在扫描电子显微镜照片上观察到了超声波辅助压实过程中颗粒之间固体桥的形成。认为固体桥的形成导致空隙空间减少，这反过来又降低了水渗入压实体的速率，从而延长了片剂崩解和药物溶解时间。研究发现，超声波辅助压实的结果受配方和超声时间的影响。粘合剂（聚乙烯吡咯烷酮）浓度和/或超声时间的增加导致超声波制备的扑热息痛片剂的断裂力显著增加。当扑热息痛与第二种材料（如二水磷酸氢钙和微晶纤维素）混合时，与不含填料的片剂相比，通过超声波辅助压实制备出了更强的压实体。认为由于超声波诱导两种材料之间的粘结而发生了积极的相互作用。总体而言，发现施加超声波可显著改善扑热息痛的压实特性。
