EFFECT OF PHYSICAL MODIFICATION ON DISSOLUTION OF NABUMETONE: A BCS CLASS II DRUGAbstract
Objective: Physically modified forms of BCS class II drug Nabumetone (NBT) was studied for dissolution in water and pharmacopoeial dissolution media (2%w/v sodium lauryl sulfate in water). Characterization was to identify the suitability of physical processing like heating, cooling, grinding, and milling operations anticipated during commercial manufacturing of dosage forms. Materials and Methods: NBT was subjected to melting followed by quench cooling, grinding, and ball milling to alter the physical characteristics. These were subjected to dissolution studies and compared the values with the raw material. Characterization was done with DSC, FTIR, and PXRD. Results: The quench cooled form of NBT exhibited low dissolution in water compared to NBT raw material and size reduced samples. In water, the cumulative percentage release (CPR) of NBT after 120 min was found to be 4.64 ± 0.04, 4.62 ± 0.09, 4.50 ± 0.07 and 4.06 ± 0.04 for NBT raw material, ground NBT, ball-milled NBT and quench cooled NBT respectively. The CPR of NBT after 120 min in 2% SLS was 86.10 ± 1.46, 92.58 ± 1.63, 90.76 ± 2.17 and 84.52 ± 1.09 for NBT raw material, ground NBT, ball-milled NBT and quenched cooled NBT samples respectively, indicating enhanced dissolution in Pharmacopoeial dissolution media. Upon characterization, a change in crystallinity pattern was noticed during physical processing, while other parameters remain unaltered. Conclusion: Physical processing can alter the crystallinity and dissolution of NBT. The low dissolution may probably due to the hydrophobic aggregates formed during processing. The crystalline rearrangement upon quench cooling might have resulted in the low water solubility compared to other forms.
J. Joseph * and J. Harindran
Department of Pharmaceutical Sciences, Centre for Professional and Advanced Studies, Cheruvandoor Campus, Ettumanoor, Kottayam, Kerala, India.
27 March 2019
21 June 2019
17 July 2019
01 December 2019