PREFORMULATION STUDIES

1. PREFORMULATION STUDIES

3. Considerations before pre-formulation studies Before initiation of pre-formulation studies, scientist need to consider the following: • The available physicochemical data (including chemical structure, different salts, potency relative to the competitive products and the dosage form etc.) • The therapeutic class of the compound, predictable/anticipated dose and the proposed route of drug administration. • Supply situation and development schedule (i.e. the time available). • The availability/accessibility of a stability-indicating assay. • The nature of the information the formulator should have or would like to have.

4. GOALS • To establish the necessary physico-chemical parameters of new drug substances. • To determine kinetic rate and stability profile. • To establish compatibility with common excipients • To provide insight into how drug products should be processed and stored to ensure their quality. • To provide a scientific data to support the dosage form design and evaluation of the product efficacy and stability

5. OBJECTIVES • To generate useful data needed in developing stable and safe dosage form that can be manufactures on a commercial scale. • To provide in-dept knowledge and understanding of the physical characteristics of a drug molecule prior to dosage form development. • To generate useful information on how to design a drug delivery system with good bioavailability.

6. Physicochemical characteristics of Drug substances in Pre-formulation studies Major areas of Pre-formulation Research • c. Solubility analysis • Ionization constant/drug pKa, • Partition co-efficient • Solubilization • Thermal effect • Common ion effect(Ksp) • Dissolution. • d. Stability analysis studies • Solid-state stability studies • Solution-state stability studies • Drug –excipient compatibility • 3. Recemization • 4. Polymerization • Physical Characteristics: • Organoleptic properties • Color, odour, taste, • Bulk characterization • Particle size & surface area • Powder flow properties • Density • Compressibility • Crystallinity • Hygroscopicity • Polymorphism • Chemical Characteristics: • Hydrolysis • Oxidation and reduction

7. Specific to drug molecules and are dependent on the chemical structure of the drug molecule/API Carried out on intended dosage form Eg. Tablets and capsules • Solid state properties • a. Physical form of Drug---Amorphous or Crystalline • b. Polymorphism • Solubility Analysis • Ionization constant • Partition co-efficient • Solubilization • Thermal effect • Common ion effect • Dissolution • Stability Analysis • Solid-state stability studies • Solution-state stability studies • Drug –excipient compatibility studies • Permeability studies • Particle properties • a. Size and shape • Powder flow properties • Bulk density • Compaction behavior

11. COLOR

12. ODOUR

14. BULK CHARACTERISTICS

17. Particle size and shape • Not only effect only physical properties of solid drug but also, in some instances effect on the biopharmaceutical behavior • Size, shape & surface morphology of drug particles affect • Flow property • Dissolution • Chemical reactivity of drugs

18. Significance of particle size • Particle size of drug may affect formulation and product efficacy • Certain physical and chemical properties of drug substances are affected by • The particle size • Drug dissolution rate • Content uniformity • Texture • Stability • Flow characteristics • Sedimentation rates • Penetrability • Suspendability • Particle size significantly influences the oral absorption profile of certain drugs • Satisfactory content uniformity in solid dosage forms depends to a large degree on particle size and the equal distribution of active ingredients throughout the formulation

19. Or Screening OR Optical Microscopy • Stream Scanning

24. Stroke’s Law

25. Manual • Transmission • a. SEM: Scanning Electron microscopy • b. TEM: Transmission Electron Microscopy