Issue link: https://www.e-digitaleditions.com/i/571156
16 September 2015 Tablets & Capsules maceutical manufacturers to focus on developmental prac- tices that help ensure—from the start—that product qual- ity aligns with patient safety, product efficacy, and product reliability. Co-processed HPMC and lactose Retalac (Meggle USA, Pawling, NY) is a DC-grade, co- processed excipient that contains equal parts HPMC and lactose and that is intended for us in MR tablets. Co- processed, the two excipients perform better than a simple blend of them. Indeed, co-processing improves the func- tional properties (e.g., flow and compressibility) of the excipients while maintaining their independent chemical characteristics [2]. The first objective of the study described here was to assess the compressibility and tabletability of a model formulation containing Retalac. The second objec- tive was to outline the advantages of an instrumented tablet press during early formulation development stages to screen and develop MR tablets made using a DC-grade excipient. Experiment Materials. Retalac was obtained from Mutchler, Harrington Park, NJ; ibuprofen from BASF, Florham Park, NJ; and magnesium stearate from Sigma-Aldrich, St. Louis, MO. Methods.A study of the compaction profile, the lubri- cant sensitivity, and the strain-rate behavior of a DC formu- lation (ibuprofen 30 percent, Retalac 69.5 percent, magne- sium stearate 0.5 percent) was performed using an instrumented benchtop, 10-station rotary tablet press (Piccola, SMI, Lebanon, NJ) equipped with 7/16-inch round, standard concave B tooling. Data acquisition, analy- sis, and data representation were performed using The Director software from SMI. One-kilogram powder blends were prepared as follows: Retalac and ibuprofen were passed through a 20-mesh sieve and magnesium stearate through an 80-mesh sieve. Powders were then combined in a V-type blender (Globepharma, New Brunswick, NJ) for 10 minutes at 20 rpm. Compaction profile. The goal of this study was to assess the effect of compression force on the powder blend's tabletability. It was performed on tablets weighing 400, 500, and 600 milligrams (mg) at compression forces rang- ing from 50 to 300 megapascals (MPa) at a constant turret speed of 25 rpm. The effect of pre-compression on the compaction profile was evaluated for 400- and 600-mg tablets. Lubricant sensitivity.This study was performed on 500-mg placebo tablets to see how different levels of lubricant (0.25 and 0.5 percent) affected tablet tensile strength at various compression forces. Strain rate. This study evaluated the effect of turret speed on variation of tablet properties. It was performed on 500- mg tablets at five different turret speeds. The flow property of the excipient, API, and powder blend was evaluated using a powder flow analyzer (Texture Technologies, Hamilton, MA). Physical and mechanical properties (weight, thickness, and breaking force) of the tablets were analyzed using a SmartTest 50 (Sotax, Westborough, MA). Tablet friability was analyzed using an FT 2 friability tester (Sotax). Tablet breaking force was normalized to account for tablet geometry (size and shape) to yield tensile strength () and is given by the following equation for round, con- vex tablets (from USP <1217>): where F = Breaking force D = Tablet diameter H = Tablet thickness W = Central cylinder thickness (tablet wall height) Tablet press instrumentation and parameterization Understanding powder behavior under dynamic condi- tions is crucial in the early development stage in order to develop robust formulations, and data obtained during development can be vital in transferring the formulation to a production-scale press. Instrumentation is also essential to a QbD approach to process development and lifecycle management. It helps researchers to identify CPPs, define the design space, and understand both the product and the process under development. These parameters are also use- ful metrics in monitoring the quality of the process after the product gains regulatory approval. Results Compaction profile. Physical testing of the tablet was performed at two stages: approximately 10 minutes after compression and 24 hours after compression. Samples were kept in a sealed container during the 24-hour holding period. The extended hold time had no noticeable effect on the thickness or friability of the samples, but it did affect the tensile strength of all the formulations studied. In tablets that included the API, tensile strength increased by 6 to 10 percent after 24 hours. This effect can occur in lac- tose-based formulations due to the amorphous particles that can absorb moisture from the air, which allows the forma- tion of crystalline bonds that were not present immediately after compression [3]. When the tabletting process included pre-compression, the increase in tensile strength was 9 to 10 percent; without it, the increase was 6 to 7 percent. This relative increase in strength derives from an increase in interparticle solid bonds. Ibuprofen and HPMC are both prone to air entrap- ment, which increases porosity and thereby reduces inter- particle contact. The relative increase in strength—coupled with thickness measurements that showed that the pre- compressed tablets were slightly thinner than those made without pre-compression—indicate that this formulation's tablets include entrapped air that was countered by the pre- compression force. 10F 2.84H 0.126H 3.15W D 2 D W D + = σ x + – 0.01 -1