Lecture1 Preformulation (1).pptx uuuuuuu

preformulation study

1. Aim of the course After Completing this course, the student will be able to: 1- Know various considerations in development of pharmaceutical dosage forms. 2- Design the dosage form based on Pre-formulation parameters. 3- Understand the concept and objective of controlled release. 4- Explain various physicochemical characteristics of drug substances and their importance in formulation of dosage form

2. Students evaluation

3. Assessment methods Midterm exam 20 marks Quiz I : 20/10/2024 10 marks Quiz 2 : 10/11/2024 10 marks Assignment 10 marks Reports about preformulation studies for different marketed drug. A report for each student individually Deadline for submitting reports 1/11/2024 Practical exam 30 marks Practical exam 1 10/11/2024 15 marks Practical exam 2 29/12/2024 15 marks Oral exam 15 marks Final Written 75 marks

4. Week Theoretical Topics Practical Topics Lecturer 1 Preformulation studies Flowability evaluation Ass. Prof / Mahmoud omr   Ass. Prof / Omaya Ali 2 Solubility Solubility determination 3 Dissolution Determination of dissolution rate 4 Partition coefficient Determination of partition coefficient 5 Melting point Particle size determination 6 Stability Stability 7 Controlled release Practical exam I 8 Matrix tablets Determination of drug release 9 Osmotic pump Kinetics 10 Matrix tablets Preparation of microspheres 11 Microcapsules Rate and order of reaction 12 Nanotechnology Transdermal patches 13 Transdermal patches Transdermal patches   14 Practical exam II 15 Final Written Exam

5. After completing this lecture, the students ... Know the concept of Preformulation. Understand different factors considered in preformulation. Differentiate between flowability and compressibility. Understand each step of preformulation. Realize the properties to be studied in preformulation.

6. Preformulation testing is the first step in the development of dosage forms of a drug substance. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients. The overall objective of Preformulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms.

7. Goals of Preformulation

8. To formulate an elegant, safe, efficacious dosage form with good bioavailability. To formulate new dosage form of already existing drug. Determination of all the properties of drug and the best suitable dosage form for the drug.

9. Pharmaceutical factors affecting preformulation studies

10. 1. Flow properties

11. Flow properties is an importance when handling a drug powder . Sufficient flow is required for uniformity of dosage form , so it is necessary to determine the flow of material in preformulation stage. Extreme increase in flow may improve weight uniformity but may reduce content uniformity through increased segregation.

12. Flowability evaluation By angle of repose

13. A static heap of powder with only gravity acting upon it will tend to a form a conical shape. There is an empirical relationship between θ and the ability of the powder to flow.

14. Relationship between angle of repose and Carr's index

15. 2. Density

16. The density of a substance is the relationship between the mass of the substance and how much space it takes up (volume). The mass of atoms, their size, and how they are arranged determine the density of a substance. Density equals the mass of the substance divided by its volume. D = m/v For the measurement of density of materials. Such techniques can be used: 1. Hydrometer (a buoyancy method for liquids). 2. Hydrostatic balance (a buoyancy method for liquids and solids).

17. 3. Compressibility

18. Compressibility is the ability of powder to decrease in volume under pressure. % compressibility = Tapped -Bulk density/Tapped density × 100

19. 4. Hygroscopicity Hygroscopicity: is the tendency of material to absorb moisture from atmosphere. Deliquescent: is the hygroscopic substance which absorb moisture from air and they can be liquefied partially or wholly forming solution. Efflorescent: a substance which loses water to form lower hydrate or become anhydrous.

20. 5. Electrostatic charge

21. Electrostatic charges are the consequence of classic attraction & repulsion effect between charges. Electrostatic charge is produced by: 1. Mechanical impact 2. Friction between two surfaces 3. Rupturing of particles Method of determination: 1. ELP (Electrical lower pressure impactor ) give detailed charge profile of aerosole particles 2. Electrostatic tester: which consists of electrostatic voltage sensing probs.

22. Determination of viscosity Capillary viscometer Falling sphere viscometer Cup and bob viscometer Cora and plate viscometer Broke feiled viscometer

23. 7. Wettability

24. Wettability of a solid is an important property with regards of formulation of solid dosage form. Adsorption at solid surface is involved in wetting. It may influence granulation of solid, penetration of dissolution fluid into tablet and granules and adhesion of coating material into tablets. Wettability is determined by contact angel. The contact angel is the angel between a liquid droplet and the surface over which it spreads.

25. Properties to be studied in Preformulation

26. Organoleptic Properties Purity Particle Size, Shape, and Surface Area Solubility Dissolution Absorption Stability testing Melting point Polymorphism Pseudopolymorphism Assay development Excipient compatibility

27. 1. Organoleptic Properties

28. Include taste, sight, smell, and touch. Modern medicines require that pharmaceutical dosage forms are acceptable to the patient. Unfortunately, many drug substances in use today are unpalatable and unattractive in their natural state and dosage forms containing such drugs particularly oral preparations, may require the addition of approved flavours and/or colours . The use of flavours applies primarily to liquid dosage forms intended for oral administration. Flavours are usually composed of mixtures of natural and synthetic materials.

29. Terminology to describe organoleptic properties

30. 2. Purity

31. Impurity can affect: - Stability: metal contamination in ppm - Appearance: off-color -Toxic impurities : aromatic amine often remedial action is simple: re-crystallization

32. Techniques used for characterizing purity

33. Thin layer chromatography (TLC) High-performance liquid chromatography (HPLC) Gas chromatography (GC) Differential scanning calorimetry (DSC)

34. Differential scanning calorimetry (DSC)

35. DSC can be used for purity analysis However, this is restricted to those compounds that are greater than 98% pure. It may be appropriate, if HPLC methods are not available, to use DSC to estimate purity, but it should be emphasized that DSC is much less accurate than HPLC in this respect.

36. 3. Particle Size, Shape, and Surface Area

37. Effects of particle size distribution and shape on: - Chemical and physical properties of drug. - Bioavailability of drug substances. - Flow and mixing efficiency of powders. -Stability, fine materials relatively more open to attack from atmospheric O 2 , heat, light, humidity, and interacting excipients than coarse materials.

38. Drawbacks of grinding

39. • material losses • static charge build-up • aggregation leading to increase hydrophobicity • polymorphic or chemical transformations

40. Determination of Surface Area

41. Brunauer-Emmett-Teller(BET) Called theory of adsorption. Most substances will adsorb a monomolecular layer of a gas under certain conditions of partial pressure (of the gas) and temperature. Knowing the monolayer capacity of an adsorbent (i.e., the quantity of adsorbate that can be accommodated as a monolayer on the surface of a solid, the adsorbent) and the area of the adsorbate molecule, the surface area can, in principle be calculated. Most commonly, nitrogen is used as the adsorbate at a specific partial pressure established by mixing it with an inert gas, typically helium. The adsorption process is carried out at liquid nitrogen temperature (-195 o C).

42. Brunauer-Emmett-Teller (BET) adsorption isotherm 1 = C - 1 P + λ [ ) P o /P ) -1 ] λ m C P o 1 λ m C λ = g of adsorbate per g of adsorbent λ m = maximum value of that λ ratio for a monolayer P = partial pressure of the adsorbate gas P o = vapor pressure of the pure adsorbate gas C = constant P, P o , and C are temperature-dependent

43. The values of λ (g of adsorbate/g of adsorbent) at various P values (partial pressure of the adsorbate gas) could be obtained from the experiment through instrument. P o ) v a p o r p res s u re o f t h e p u re a d s o r b a t e g a s ) ca n be obtained from the literature. Plotting the term against P/P o will obtain a straight line with slope = (C - 1)/ λ m C intercept = 1/ λ m C The term C and λ m can readily be obtained . 1 λ [ ) P o /P ) -1 ]

44. Particle Diameter and Surface Area