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A key goal in pharmaceutical development of oral dosageformBioavailability is defined as the rate and extent to which the active ingredient or active moiety is absorbed for a drug product and becomes available at the site of action.Factors Influencing Bioavailability:1. Physicochemical attributes of Drug substancesDrug solubility and dissolution rateParticle size and effective surface areaBulk and tapped density, Powder flow characterizationPolymorphism, amorphism and hygroscopicityPseudopolymorphism (hydrates/solvates)Salt form of the drugLipophilicitypKa of the drug and pHDrug stability (% volatile, LOD, moisture content)2. Dosage Form Characteristics and Pharmaceutical Ingredients

Disintegration time (tablets/capsules)dissolution timeManufacturing variables (method of granulation, compression force, intensity of packing of capsule contents)Pharmaceutical ingredient (excipients/adjuvants)Nature and type of dosage formProduct age and storage conditionPharmaceutical factors

QUALITY BY DESIGN FOR PROCESS OPTIMISATION OF A NOVEL ORAL SOLID DOSAGEFORM Dosage Form Design: Traditional Vs Systematic Approach

Design and development of an immaculate drug product or pharmaceutical process usually involves multiple objectives under its ambit. For decades, this task has been endeavored through trial and error, supplemented by the previous experience, knowledge and wisdom of the formulator. The modification of a formulation is carried out by the analysis of its composition and influence of process factors on dosage form characteristics, changing any one at a time. Using this approach, the solution of a specific problematic property can be achieved, but attainment of the true optimum composition or process can never be guaranteed. The final product may be satisfactory but sub-optimal, as a better formulation might still exist for the studied conditions. Thus, in the traditional approach the primary aim of the formulator may not be in designing the best formulation, but finding a suitable solution under the given set of restrictions.The aforementioned drug product inconsistencies are generally due to inadequate knowledge of causal factor and response relationship. Nowadays, systematic approaches, usually called as optimization techniques, are being widely practiced to alleviate such inconsistencies. These encompass experimental designs, mathematical equations and graphic outcomes, depicting a complete picture of variation of the response as a function of the factor.Systematic approaches are thus far more advantageous, possess greater benefits and overcome various pitfalls inherent to the traditional approaches as these are require fewer experiments to achieve an optimum formulation, reveal interactions, yield the best solution in the presence of competing objectives, make problem tracing and rectification quite easier, simulate the product or process performance using model equation, comprehend the process to assist in formulation development and subsequent scale-up.

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).Active pharmaceutical ingredient GeneralStress testingSelection of batchesContainer closure systemSpecifi cationTesting frequencyStorage conditionsStability commitmentEvaluationStatements and labellingOngoing stability studiesFinished pharmaceutical productGeneralSelection of batchesContainer closure system Testing frequencyStorage conditionsStability commitmentEvaluationStatements and labellingIn-use stabilityVariationsOngoing stability studies Guidelines Current Approach Quality assured by testing and inspectionData intensive submission disjointed information without big pictureSpecifications based on batch historyFrozen process, discouraging changesFocus on reproducibility often avoiding or ignoring variation QbD Approach Quality built into product & process by design, based on scientific understandingKnowledge rich submission showingproduct knowledge & process UnderstandingSpecifications based on product performance requirementsFlexible process within design space, allowing continuous improvementFocus on robustness understanding and controlling variation