VALIDATION OF A SIMPLE DISINTEGRATION TEST FOR RAPIDLY DISINTEGRATING TABLETS

Morris Auditorium

Objective. For rapidly disintegrating tablets (RDTs), the current USP method does not accurately measure very short disintegration times nor discriminate between different RDTs formulations. For the purpose of evaluating the effect of making changes in RDT formulations on disintegration time and for formulation development, a simple and novel disintegration test was developed and validated. The impact of disintegration medium’s temperature and volume and the agitation level on various RDTs’ disintegration was evaluated in this study. Background. The disintegration test, although not a required USP test, it is very crucial for drug development, especially for the development of rapidly disintegrating tablet (RDT) formulations. The current USP method for measuring the disintegration time (DT) of RDTs does not accurately measure very short DTs nor discriminates between different RDT formulations. Several methods have been developed before to measure the DT of RDTs, however, they lacked the simplicity, the adaptability by other laboratories, or the ability to control for various test conditions that impact the DT. Therefore, we designed and developed a simple adaptable but sensitive disintegration test to evaluate the effect of making formulation changes on RDTs’ DT. The impact of disintegration medium’s temperature and volume and the agitation level on various RDTs’ disintegration was evaluated in this study. Methods. The disintegration apparatus consisted of a stainless steel cylindrical basket, 36.8 ± 0.1 mm height and 23.6 ± 0.1 mm diameter, and mesh size 10. A motorized shaft was used to induce three levels of agitation (40 rpm, 60 rpm, and 80 rpm). Two volumes of deionized water (2 mL or 20 mL), as a disintegration medium, were evaluated at 37 oC or 25 oC. Five different RDTs formulations were used to validate this disintegration test. Of which, two sublingual RDTs sizes, 150 mg and 50 mg tablet-weight, containing 2 18 mg atropine sulfate (AS) were used to evaluate the effect of tablet size on disintegration time. Three RDTs containing 2 mg, 4 mg, and 8 mg AS and weighing 50 mg were used to evaluate effect of drug load on tablet disintegration time. Claritin RDTs (RediTabs®) containing 10 mg loratadine and weighing 20 mg were used as an example for Zydis® fast dissolve technology to evaluate the ability of this disintegration test to measure extremely short disintegration times. The disintegration endpoint was determined as defined in USP disintegration test. Means±SD (n=3) were calculated and statistically compared using ANCOVA and Tukey-Kramer test, p < 0.05. Results. All the three covariates (medium volume, agitation level, and medium temperature) affected the RDTs’ disintegration time significantly (p < 0.05). There was a significant disintegration difference (p < 0.05) between the two RDTs sizes, 150 and 50 mg (93±2 and 18±1 sec at 2 mL, 40 rpm, and 25 °C). Also, there was significant disintegration difference (p < 0.05) was detected between various drug loads, 2 mg, 4 mg, and 8 mg (18±1, 22.6±0.3, and 26±1 sec at 2 mL, 40 rpm, and 25 °C). This test was able to measure a significant disintegration difference (p < 0.05) between Claritin (6.8±0.3 sec) and all the previous three drug loads. Conclusion. This disintegration test was simple, robust, and can be easily adapted for measuring very small disintegration differences during RDTs formulation development or for comparing various RDTs formulations and technologies. Disintegration medium’s volume and temperature and the agitation level are important factors that should be considered during the measurement of RDSTs’ disintegration time. Grants. SACM