Category: Manufacturing and Bioprocessing
Purpose: Process optimization for dual release (immediate and sustained) metformin hydrochloride tablets with at-line NIR technique
Methods: Dual release metformin tablets were developed by direct compression method. The immediate release portion was comprised of carbopol 934, sodium CMC and lactose as excipients. The sustained release portion was comprised of HPMC K100M, lactose and cross povidone. The API and excipient blend was blended on a turbula mixer for 10mins. The blend was compressed using Natoli (RP- 10A) single station tablet press. The tablets are analyzed for their hardness, thickness and weight variation. The content uniformity is evaluated using UV- visible spectrophotometry and FT-NIR spectrophotometry. FT-NIR spectrophotometer Antaris II (Thermo Fisher Scientific), standard tablet transmission module was used to obtain spectras and TQ analyst software was used to analyze and calibrate the model.
Results: Immediate release was achieved within 30mins and sustained release was achieved for upto 8hrs. Tablets containing different % active concentration (80-120%) were used to develop calibration model for FT-NIR technique. In this study, near-infrared (NIR) transmittance chemometric calibrations of the active substance content of a pharmaceutical tablet were developed using partial least-squares regression (PLS). A calibration on all four dosages resulted in a prediction error expressed as the root mean squared error of cross-validation (RMSECV) of 0.30% w/w for the NIR transmittance calibration. Specially prepared calibration batches for each dosage were added to the first sample set, covering the range 80–120% of the nominal content and NIR transmittance calibrations on this set—containing coated as well as uncoated tablets—gave a further reduction in prediction errors to 0.2–0.281% w/w. . The calibration models were validated in terms of measurement accuracy, repeatability, precision, robustness and transferability. Robustness assessment involved challenging the model with tablets incorporating variations in hardness, excipient vendors, excipient content and excipient particle size. The methods exhibited excellent measurement accuracy based on 15 batches (ten tablets for each batch) evaluated. The transferability of the developed NIR methods was demonstrated by comparing the NIR CU results.
Conclusion: The result indicates that the NIR method can be used as a suitable alternative to the HPLC or UV method for rapid tablet CU release test for bilayer release drug tablets.