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QUALITY BY DESIGN FOR PROCESS OPTIMISATION OF A NOVEL ORAL SOLID DOSAGE FORMICH Q8 Pharmaceutical Development

Pharmaceutical Development

Quality cannot be tested into products; quality should be built-in by design Introduces a new (optional) development paradigm, Quality by Design (QbD), a systematic approach to pharmaceutical development.

What is QbD?

Quality by Design is: 1) a scientific,risk based,holistic and proactive approach to pceutical development. 2) a deliberate design effort from product conception through commercialization. 3)a full understanding of how product attributes and process relate to product performanceActive pharmaceutical ingredient General Stress testing Selection of batches Container closure system Specifi cation Testing frequency Storage conditions Stability commitment Evaluation Statements and labelling Ongoing stability studies Finished pharmaceutical product General Selection of batches Container closure system Testing frequency Storage conditions Stability commitment Evaluation Statements and labelling In-use stability Variations Ongoing stability studies ICH Guidelines for Active pharmaceutical ingredient And Finished pharmaceutical product :Dosage Form Design: Traditional Vs Systematic Approach Current Approach Quality assured by testing and inspection

Data intensive submission disjointed information without big picture

Specifications based on batch history

Frozen process, discouraging changes

Focus on reproducibility often avoiding or ignoring variation QbD Approach Quality built into product & process by design, based on scientific understanding Knowledge rich submission showingproduct knowledge & process Understanding Specifications based on product performance requirements Flexible process within design space, allowing continuous improvement Focus on robustness understanding and controlling variation Enhancement of Solubility of Digoxin using QbD PrincipleWhat is Solubility ? Solubility may be defined as the amount of a substance that dissolves in a given volume of solvent at a specified temperature.More specifically, compound solubility can be defined as unbuffered, buffered, and intrinsic solubility. Unbuffered solubility, usually in water, means solubility of a saturated solution of the compound at the final pH of the solution (which may be far from pH 7 due to self-buffering).By enhancement of solubility we can enhance the Bioavailability of Drug.

Enhancement Of BioavilabilityEnhancement Of BioavilabilityMany poorlysolubleand slowly dissolving drugs currently are marketed in microcrystalline form.The bioavailability of digoxinincreasedfrom 40% to approximately 80% to 97% by reducing the particle size from 100 to approximately 10 nm. . Chloramphenicol palmitate and ritonavir provide goodexamplesof howpolymorphismcan influence drug dissolution and, thus, drugsolubility. Therefore, many poorlysolubleand slowly dissolving drugs currently are marketed in a micronized or microcrystalline form Enhancement Of BioavilabilityIncrease in solubility of Benzathin using salt form

Plot of Dissolved Drug Concentration versus Time