title: The effect of ultrasonic vibration on the compaction characteristics of paracetamol.
abstract: 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.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Levina
authors.forename: M H
authors.initials: MH
authors.lastname: Rubinstein
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D004339:Drug Compounding; D008855:Microscopy, Electron, Scanning; D013696:Temperature; D014465:Ultrasonics
chemical_list: D000082:Acetaminophen