APPLICATION OF NEAR INFRARED SPECTROSCOPY FOR ENDPOINT DETERMINATION OF BLENDING AND INFLUENCE OF LOADING ORDER

Objective: This study aimed to apply near-infrared spectroscopy along with a thief as a tool to determine the endpoint of the blending process. Methods: The calibration model was constructed by partial least square regression. The best model was applied to determine the endpoint of the blending process, also the effect of loading order on the endpoint for the blending of the formulation containing a low concentration of the active pharmaceutical ingredient. Results: The best partial least square regression model yielded the lowest root mean square error of calibration of 1.4004, the lowest root mean square error of prediction of 1.4108 and the highest correlation coefficient of 0.9921. Validation study revealed the reference values were not statistically different from those of the predicted values. The model could predict the endpoint of the blending process with acceptable precision and accuracy. Standard deviation of the content of active pharmaceutical ingredients was ≤ 3% of the target after eighteen minutes of the blending process, which indicated the uniformity of powder blends. Additionally, the model revealed the order of powder loading slightly affected the blending time. The protocol that loaded the active pharmaceutical ingredient first or last needed a longer time to achieve the uniformity of blend. Conclusion: NIR spectroscopy is the rapid and effective tools that could be applied to study the blending process in the pharmaceutical manufacturing

Complete Cocrystal Formation during Resonant Acoustic Wet Granulation: Effect of Granulation Liquids

The manufacturing of solid pharmaceutical dosage forms composed of cocrystals requires numerous processes during which there is risk of dissociation into parent molecules. Resonant acoustic wet granulation (RAG) was devised in an effort to complete theophylline–citric acid (THPCIT) cocrystal formation during the granulation process, thereby reducing the number of operations. In addition, the influence of granulation liquid was investigated. A mixture of anhydrous THP (drug), anhydrous CIT (coformer), and hydroxypropyl cellulose (granulating agent) was processed by RAG with water or ethanol as a granulation liquid. The purposes were to (i) form granules using RAG as a breakthrough method; (ii) accomplish the cocrystallization during the integrated unit operation; and (iii) characterize the final solid product (i.e., tablet). The RAG procedure achieved complete cocrystal formation (>99%) and adequately sized granules (d50: >250 μm). The granulation using water (GW) facilitated formation of cocrystal hydrate which were then transformed into anhydrous cocrystal after drying, while the granulation using ethanol (GE) resulted in the formation of anhydrous cocrystal before and after drying. The dissolution of the highly dense GW tablet, which was compressed from granules including fine powder due to the dehydration, was slower than that of the GE tablet