Preformulation Power Point Presentation
Download as PPTX, PDF2 likes1,306 views
The document outlines the preformulation process in drug development, emphasizing the importance of understanding physicochemical properties that affect drug performance and formulation stability. It covers key aspects such as bulk characterization, solubility analysis, stability testing, and analytical techniques crucial for developing effective dosage forms. Students completing this unit will gain comprehensive insights into preformulation's role in creating stable and efficacious pharmaceuticals.
Preformulation Power Point Presentation
- 1. PREFORMULATION By B. S. Bhanage-Parande Assistant Professor Pharmaceutics Department
- 2. Unit Outcome • On completion of this unit students will able to understand the concept of preformulation studies. • Also they will able to understand the various aspects of preformulation. • Students will get clear idea about role of preformulation in the development of new stable dosage form. • They will learn about the concept of stability.
- 3. Contents • Introduction (Drug discovery and development) • Concept of preformulation • Aspects of Preformulation • Analytical Techniques
- 4. Drug Discovery to developmet New Chemical Entity: 1. By Organic Synthesis 2. Molecular Modification 3. Isolation of Plants Preclinical Studies: Phharmaco logy ADME Toxicology Preformulation Formulation Development
- 5. What is preformulation? • Preformulation involves the study of physicochemical properties of new compound which could affect on the drug performance and which will helps to develop a stable and efficacious dosage form. • It confirms that there is no any significant barrier to the drug development process.
- 6. Aspects of Preformulation 1.Bulk Characterization: Crystellinity and Polymorphism Hygroscopicity Fine Particle Characterization Powder flow Properties 2. Solubility Analysis Ionization Constant pka Ph solubility Profile Common Ion Effect Thermal Effect
- 7. Solubilization Partition Coefficient Dissolution 3. Stability Analysis: Stability in Toxicology Formulation Solution Stability Solid State Stability
- 9. How crystallinity will affect on Drug? • Crystal habit or its internal structure of the drug may affect on the physicochemical properties such as flowability, hygroscopicity chemical stability etc. (Habit- is the outer structure of the cryatal and Internal structure is the arrangement of molecules within the solid)
- 10. How crystallinity will affect on Drug? • Crystal habit or its internal structure of the drug may affect on the physicochemical properties such as flowability, hygroscopicity chemical stability etc. (Habit- is the outer structure of the cryatal and Internal structure is the arrangement of molecules within the solid)
- 12. • Continued…..
- 13. Crystallinity Affect on Drug Development Amorphous form of crystal Having high solubility high Dissolution but thermodynamically instable Nonstoichiometric Adducts Solvent molecule entrapment within crystal lattice, should be avoided for development. (Lack of reproducibility) Stoichiometric Adducts Conversion of anhydrous comp. to hydrats within the dosage form may reduce the dissolution rate and exent of drug absorption.
- 14. Polymorphism:
- 15. • It is the ability of a compound to cryastallize in more than one form with different internal structure. • Polymorphism affects on the solubility and chemical stability of the drug molecules, which can have a big impact on the bioavailability and its development process. • While performimg Preformulation, it it important to identify the polymorph which is stable at room temperature and to determine that whether the polymorphic conditions are possible within the temperature range used for stability studies and processing
- 16. Hygroscopicity: • Water soluble salt forms are having tendency to adsorbe water.and generally it depends on the atmospheric humidity, temperature, surface area, exposure etc. • And this mosture adsorption will generally influence on chemical stability, flowablity, comactibility. • (Test for moisture content: samples are placed in open containers by making thin powder bed for achievingmore more exposure to atm. Moisture. Then the samples are exposed to range of relative humidities prepared with saturated aq. Salt solutions. )
- 17. • Moisture uptake can be checked at time points of 0-24 hrs and storage of 0-12 weeks. • Analytical methods: TGA, Gravimetry, karl Fissure Apparstus.
- 18. Fine particle characterization: It should be tested during preformulation because, it is required to produce homogeneous dosage form and to maximise the surface area for internal actions.
- 19. • Study of particle size give an information about solubility, dissolution rate, absorption, etc. • particle size and surface area of a solid drug are inversely related to each other.
- 20. Powder flow properties • The flow properties of a powder will determine the nature and quantity of excipients needed to prepare a compressed or a powder dosage form.
- 21. Solubility Analysis • AQUEOUS SOLUBILITY • Important objective of the preformulation studies that to set a method method for making solutions of the drug. • Orally administered drug must dissolve in the aqueous fluid of the GIT prior to its absorption. • Solubility can be improved by addition of co-solvents
- 22. Drug pKa / Ionization at physiological pH • pKa is the dissociation constant of a drug. • The nonionized substances are lipid soluble thus dissolve in lipid material of the membrane and transported by passive diffusion. • Where as, the ionized substances is a lipid insoluble therefore permeation is slow.
- 23. Percent ionisation can be calculatedas For Acidic compounds: % ionized = 100/ 1+ antilog (pKa – pH) For Basic compounds: % ionized = 100/ 1+ antilog (pH – pKa) Degree of ionization depends up on the pH. for acidic drugs pKa ranges from 3-7.5. for basic drugs pKa ranges from 7-11.
- 24. Partition coefficient • Partition coefficient is the measure of lipophilicity of the drug. • Partition coefficient is a ratio of equilibrium concentration of drug in oil phase to equilibrium concentration of drug in aqueous phase . K=Co/Cw where, Co-organic phase concentration Cw-aqueous phase concentration
- 25. • Following administration, the drug must travel through a variety of membranes to gain access to the target area. • Drug with extremely high partition co- efficient (i.e. very oil-soluble ) readily penetrate the membranes. • While drugs with excessive aqueous solubility i.e. low oil/water partition co- efficient cannot penetrate the membrane.
- 26. Dissolution • To know the gastrointestinal absorption & other physicochemical properties. • The speed at which a drug substance dissolves in a medium is called its dissolution rate. • For a chemical entity, its acid, base, or salt forms, as well as its physical form (e.g., particle size), may result in substantial differences in the dissolution
- 28. Stability studies • In this study includes both solutions and solid- state experiments under various conditions for handling, formulation, storage, and in vivo administration. • Solution phase stability: The effect of pH on stability is important in the development of both oral and Parenteral dosage forms • Acid sensitive drugs protected from highly acidic environment of the stomach by coating it with suitable polymers. Solid phase stability depends on several factors like temperature, pH, humidity, hydrolysis, oxidation, etc…
- 29. Compatibility • Compatibility test play a very important role in the preformulation studies of oral dosage forms. • Problems arise because of the interaction with other drug substances and with preservatives, stabilizers, dyes, and flavors. • It is important for the formulator of a new drug substance to know with which excipients he can work and which he cannot.
- 31. Analytical Methods Various analytical techniques are available for the investigation of the physicochemical properties and determination of impurity of new drug molecules. • These includes: 1. Microscopy 2. Spectroscopy 3. Chromatography
- 32. Microscopy • In this technique substances are examined under the microscope. • It gives information about shape, thickness, particle size, etc. of drug molecules. • By this method we can study crystal morphology, difference between polymorphic character of molecule
- 33. UV Spectrometry • When organic molecules in solution, or as liquid, are exposed to light in the visible and ultraviolet light regions of spectrum, they absorb light of particular wavelengths depending on the type of electronic transition that is associated with the absorption. • Spectrophotometry can be used to study to enzyme reaction and to evalute the effect of drug on enzyme. • UV study of compounds gives information regarding unsaturation of compounds.
- 35. IR Spectroscopy • The study of the interaction of electromagnetic radiation with vibrational and rotational resonances within a molecular structure is termed as IR Spectroscopy. • IR has the ability to differentiate isomers groups such as Cis- trans double bond compound. • Gives an information regarding functional group present in new drug molecule.
- 37. X-RAY Diffraction • When a beam of non homogenous x-rays is allowed to pass through a sample the x-ray beam is diffracted & it is recorded by means of photographic plates . • Single Crystal X-ray provides the most complete information about the solid state. • It is used to differentiate the amorphous and crystalline forms.
- 39. Thermal Analysis • Differential scanning calorimetry (DSC) and differential thermal analysis(DTA) are particularly useful in preformulation studies including purity, polymorphism, solvation, degradation, and excipient compatibility. • It measures physical or chemical changes of drug molecules. Thermigravimetric analysis • Used to detect the existange and stability of solvated drug molecule.
- 40. Chromatography • In the preformulation studies, chromatographic techniques such as TLC, HPLC,GC carrying a major role. • The major advantages are direct analysis of aqueous samples, high sensitivity, and specific determination of drug concentration, separation of drug from impurities or degradation products.
- 41. References: • Loyed V. Allen, Jr. Howard C. Ansel “Ansel’s Pharmaceutical dosage forms and Drug Delivery systems”, 10th Edition, 35-38 • Leon Lachman, Herbert A. Liberman, Joseph L. Kanig, “The theory and Practice of Industrial Pharmacy”, Third Edition, Varghese Publication House, 171.
- 42. Thank You
Editor's Notes
- #14: Stoiciometric adducts also known as solvates which are basically a molecular complex which has incorporated the crystalizing solvent molecules into specific sites of crystals. When incorporated solvent is water the complex is known as hydrate. A comp. not containing any water within its crystal is anhydrous. Identificatio of hydrate comp. are imp coz their aq. Solubilities are less than anhydrous comp.