PHARMAECUTICALS ANALYSIS.pptx tablet compreesion granulation api drying

pharmaceuticals

1. Pharmaceutical analysis Presented by VINCY SHAMLEY EBEN

2. Process Analytical Technology (PAT) Process Analytical Technology (PAT) is a framework introduced by the FDA to ensure consistent product quality in pharmaceutical manufacturing. Spectroscopy-based PAT techniques, such as Near-Infrared (NIR), Raman, and UV-Vis spectroscopy, enable real-time monitoring and control of critical process parameters (CPPs) and critical quality attributes (CQAs). These techniques enhance product quality, reduce variability, and optimize manufacturing processes by offering real-time insights into the production stages. PAT enhances process understanding, supports Quality by Design ( QbD ), and minimizes batch-to-batch variability. It helps pharmaceutical companies comply with regulatory requirements by ensuring continuous monitoring, thereby reducing the need for end-product testing and increasing overall efficiency.

3. Applications of Spectroscopy in Pharmaceutical Processes 1. Reaction Monitoring Spectroscopy (NIR, Raman, UV-Vis) allows real-time monitoring of chemical reactions. Enables precise tracking of reaction progress by analyzing key molecular vibrations and electronic transitions. Provides early detection of reaction deviations, impurity formation, and endpoint determination. Reduces batch failures and improves reproducibility by optimizing reaction kinetics. Helps maintain reaction consistency and efficiency in large-scale pharmaceutical production. Example: Monitoring esterification or hydrolysis reactions in API synthesis, ensuring complete conversion to the desired product. Advanced Example: Online Raman spectroscopy is used to track polymorphic transformations during reaction-based crystallization processes, ensuring batch-to-batch reproducibility.

4. 2. Crystallization In-line Raman and NIR spectroscopy monitor the crystallization process by assessing nucleation, growth, and transformation of polymorphic forms. Helps control supersaturation levels, solvent composition, and cooling rates to ensure consistency. Prevents undesired polymorphic conversions that may affect drug bioavailability and stability. Reduces the risk of batch failures due to irregular crystal formation. Enhances crystal size distribution (CSD), ensuring uniform dissolution rates in the final formulation. Example: Controlling the crystallization process of Ritonavir to prevent undesired polymorphs from affecting dissolution rates. Advanced Example: Real-time Process Raman Spectroscopy in batch cooling crystallization to ensure the consistency of active pharmaceutical ingredients (APIs).

5. 3. API Drying NIR spectroscopy detects real-time residual solvent levels, ensuring appropriate drying times. Prevents over-drying, which can lead to API degradation and instability. Ensures compliance with ICH guidelines by maintaining acceptable moisture levels. Reduces energy consumption and process time by optimizing drying parameters. Prevents retention of volatile solvents, reducing the risk of toxicity. Example: Solvent removal from APIs post-crystallization to meet regulatory standards before formulation. Advanced Example: Using in-line TDLAS ( Tunable Diode Laser Absorption Spectroscopy) to precisely monitor residual solvents during vacuum drying processes.

6. 4. Nano Milling Real-time particle size monitoring using PAT tools like Focused Beam Reflectance Measurement (FBRM) and NIR spectroscopy. Ensures uniform particle size reduction for improved dissolution and bioavailability. Minimizes variability between batches, ensuring consistency in final dosage forms. Optimizes milling time and energy usage to enhance manufacturing efficiency. Example: Nano-sizing poorly soluble drugs like fenofibrate for enhanced absorption. Advanced Example: PAT-enabled dynamic light scattering (DLS) is used to monitor the stability and aggregation behavior of nanocrystals in suspension.

7. 5. Hot-Melt Extrusion (HME) NIR and Raman spectroscopy monitor polymer-drug mixing in real time. Ensures uniform dispersion of API within the polymer matrix for consistent drug release. Detects phase separation or degradation due to excessive heat exposure. Improves process efficiency by optimizing extrusion conditions. Example: Production of amorphous solid dispersions to enhance the solubility of poorly water-soluble drugs. Advanced Example: Real-time FTIR (Fourier-transform infrared spectroscopy) is applied to monitor API-polymer interactions and phase transitions in HME processes.

8. 6. Granulation (Wet & Dry) Spectroscopy (NIR, Raman) monitors granulation parameters, including moisture content, granule size, and binder distribution. Prevents under-granulation (leading to poor tablet compressibility) or over-granulation (causing tablet hardness issues). Enhances blend homogeneity and dissolution properties of the final dosage form. Reduces waste and rework by ensuring batch-to-batch consistency. Example: Manufacturing of extended-release tablets where uniform granulation is critical for controlled drug release. Advanced Example: Real-time monitoring using spatially resolved spectroscopy (SRS) in high-shear wet granulation to optimize binder addition.

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