title: Instrumented roll technology for the design space development of roller compaction process.
abstract: Instrumented roll technology on Alexanderwerk WP120 roller compactor was developed and utilized successfully for the measurement of normal stress on ribbon during the process. The effects of process parameters such as roll speed (4-12 rpm), feed screw speed (19-53 rpm), and hydraulic roll pressure (40-70 bar) on normal stress and ribbon density were studied using placebo and active pre-blends. The placebo blend consisted of 1:1 ratio of microcrystalline cellulose PH102 and anhydrous lactose with sodium croscarmellose, colloidal silicon dioxide, and magnesium stearate. The active pre-blends were prepared using various combinations of one active ingredient (3-17%, w/w) and lubricant (0.1-0.9%, w/w) levels with remaining excipients same as placebo. Three force transducers (load cells) were installed linearly along the width of the roll, equidistant from each other with one transducer located in the center. Normal stress values recorded by side sensors and were lower than normal stress values recorded by middle sensor and showed greater variability than middle sensor. Normal stress was found to be directly proportional to hydraulic pressure and inversely to screw to roll speed ratio. For active pre-blends, normal stress was also a function of compressibility. For placebo pre-blends, ribbon density increased as normal stress increased. For active pre-blends, in addition to normal stress, ribbon density was also a function of gap. Models developed using placebo were found to predict ribbon densities of active blends with good accuracy and the prediction error decreased as the drug concentration of active blend decreased. Effective angle of internal friction and compressibility properties of active pre blend may be used as key indicators for predicting ribbon densities of active blend using placebo ribbon density model. Feasibility of on-line prediction of ribbon density during roller compaction was demonstrated using porosity-pressure data of pre-blend and normal stress measurements. Effect of vacuum to de-aerate pre blend prior to entering the nip zone was studied. Varying levels of vacuum for de-aeration of placebo pre blend did not affect the normal stress values. However, turning off vacuum completely caused an increase in normal stress with subsequent decrease in gap. Use of instrumented roll demonstrated potential to reduce the number of DOE runs by enhancing fundamental understanding of relationship between normal stress on ribbon and process parameters.
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA. Electronic address: vishwas.nesarikar@bms.com.
authors.forename: Vishwas V
authors.initials: VV
authors.lastname: Nesarikar
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Nipa
authors.initials: N
authors.lastname: Vatsaraj
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Patel
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: William
authors.initials: W
authors.lastname: Early
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Preetanshu
authors.initials: P
authors.lastname: Pandey
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Sprockel
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Drug Product Science and Technology, Bristol-Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Jerzewski
authors.affiliation: Miller Pharmaceutical Technology, 16 Crown Ridge Road, Travelers Rest, SC 29690, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Miller
authors.affiliation: Milev Pharmaceutical Technology Consulting, 27 Moran Road, West Orange, NJ 07052, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D004339:Drug Compounding; D004867:Equipment Design; D005079:Excipients / Q000737:chemistry*; D005240:Feasibility Studies; D017276:Friction; D007785:Lactose / Q000737:chemistry; D054327:Lubricants / Q000737:chemistry; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D016062:Porosity; D011312:Pressure; D012822:Silicon Dioxide / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D013718:Tensile Strength; D014160:Transducers, Pressure
chemical_list: D003102:Colloids; D005079:Excipients; D054327:Lubricants; D004364:Pharmaceutical Preparations; D013229:Stearic Acids; C031183:stearic acid; D012822:Silicon Dioxide; D002482:Cellulose; D007785:Lactose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose