title: Introduction of a theoretical splashing degree to assess the performance of low-viscosity oils in filling of capsules.
abstract: These days an alternative to soft capsules is liquid-filled hard capsules. Their filling technology was investigated earlier with highly viscous formulations, while hardly any academic research focused on low-viscosity systems. Accordingly, this work addressed the filling of such oils that are splashing during the dosing process. It was aimed to first study capsule filling, using middle-chain triglycerides as reference oil, in order to then evaluate the concept of a new theoretical splashing degree for different oils. A laboratory-scale filling machine was used that included capsule sealing. Thus, the liquid encapsulation by microspray technology was employed to seal the dosage form. As a result of the study with reference oil, the filling volume and the temperature were found to be significant for the rate of leaking capsules. The filling volume was also important for weight variability of the capsules. However, most critical for this variability was the diameter of the filling nozzle. We proposed a power law for the coefficient of weight variability as a function of the nozzle diameter and the obtained exponent agreed with the proposed theory. Subsequently, a comparison of different oils revealed that the relative splashing degree shared a correlation with the coefficient of the capsule weight variability (Pearson product moment correlation of r=0.990). The novel theoretical concept was therefore found to be predictive for weight variability of the filled capsules. Finally, guidance was provided for the process development of liquid-filled capsules using low-viscosity oils.
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences Northwestern Switzerland, Gründenstr. 40, CH-4132, Muttenz, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Niederquell
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D002214:Capsules; D004339:Drug Compounding / Q000379:methods; D005079:Excipients; D006801:Humans; D008962:Models, Theoretical; D009821:Oils / Q000737:chemistry*; D004364:Pharmaceutical Preparations; D011786:Quality Control; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods / Q000706:statistics & numerical data; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry* / Q000378:metabolism; D014783:Viscosity
chemical_list: D002214:Capsules; D005079:Excipients; D009821:Oils; D004364:Pharmaceutical Preparations; D014280:Triglycerides; C022834:miglyol 812