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Preformulation study by Pavan B Zalte

  1. Sinhgad Technical Education Society’s Sinhgad institute of pharmacy narhe, Pune 3/17/2023 1 Presented by – Mr. Pavan B. Zalte 1st year M. Pharm (Pharmaceutics) Guided by- Prof. Supriya Nikam Department of pharmaceutics
  2. Introduction Objectives Physico-chemical properties 1. Organoleptic character 2. Bulk character 3. Solubility character 4. Stability character 3/17/2023 2 Seminar will cover…
  3. PREFORMULATION Introduction 3/17/2023 3 Investigation of physical, chemical and mechanical properties of drug molecule in order to develop safe, effective, and stable dosage form. This information may dictate many of subsequent event & approaches in formulation development. This first learning phase is called as preformulation
  4. To establish the physicochemical parameters of drug entity To determine its kinetics and stability To establish its compatibility with common excipients It provides insights into how drug products should be processed and stored to endure their quality Objectives 3/17/2023 4
  5. Physico- chemical characteristic of dug Organoleptic character Bulk character Solubility character Stability character Physicochemical properties of drug 3/17/2023 5
  6. • Colour, odour, taste of the drug must be recorded 3/17/2023 6 COLOUR ODOUR TASTE white Pungent Acidic Cream yellow Sulphurous Bitter tan Fruity Bland shiny Aromatic Intense Odourless Sweet Tasteless Organoleptic characters
  7. 3/17/2023 7 Physicochemical properties of drug Bulk character Hygroscopicity Powder flow properties Fine particle characterization Crystallinity & polymorphism
  8. Crystallinity • A crystalline particle is characterized by definite external and internal structures. • Crystal habit - external shape of a crystal • Polymorphic state - refers to the definite arrangement of molecules inside the crystal lattice. • During crystallization, molecule may arrange themselves in various geometric configurations, resulting in distinct packing arrangement or orientation in crystal structure. 3/17/2023 8
  9. 3/17/2023 9 Various crystal forms
  10. • Amorphous: Amorphous drug has atoms or molecules randomly placed (without definite structure) within them. The amorphous form is of higher thermodynamic energy, greater solubility as well a higher dissolution rate than the corresponding crystalline form. 3/17/2023 10 Low mobility (crystalline) Moderate mobility (Amorphous)
  11.  It is the ability of the compound to crystallize as more than one distinct crystalline species with different internal lattice.  Polymorphs are of 2 type • Enantiotropic • Monotropic  The polymorph which can be reversibly changed from one form into another by varying temp or pressure is called as enantiotropic polymorph. Eg. Sulphur. 3/17/2023 11 Polymorphism
  12. Polymorph which is unstable at all temperature & pressure is called as Monotropic polymorph. Eg. Glyceryl stearate. Polymorphs differ from each other with respect to their physical property such as • Solubility • Melting point • Density • Hardness • Compression characteristic Eg. Chloromphenicol exist in A,B & C forms, of these B form is more Stable & most preferable. 3/17/2023 12
  13. Methods for analysing polymorphs • Microscopy • Optical crystallography • DSC (Differential Scanning Calorimetry) • TGA (Thermogravimetric Analysis) • XRD (X Ray Diffraction) • IR (Infra Red) • SEM (Scanning Electron Microscopy) 3/17/2023 13
  14. Hygroscopicity • Many drug substances have tendency to adsorb atmospheric moisture. • Hygroscopicity classified into four classes: 1. Slightly hygroscopic: increase in weight is >0.2%w/w & <2%w/w 2. Hygroscopic: increase in weight is >2%w/w & <15%w/w 3. Very hygroscopic : increase in weight is >15%w/w. 4. Deliquescent : Sufficient water is adsorbed to form solution Change in moisture level can influence • Chemical stability • Flowability • Compactibility 3/17/2023 14
  15. •Powder flow properties 3/17/2023 15 Test to evaluate the flowability of powder Carr’s compressibility index Hausner ratio The angle of repose (θ)
  16. • A volume of powder is filled into a glass cylinder and repeatedly tapped for a known duration. • The volume of powder after tapping is measure. Bulk density = weight/ bulk volume Tapped density = weight/ true volume • Carr’s compressibility index 3/17/2023 16
  17. 3/17/2023 17
  18. • Carr’s compressibility index 3/17/2023 18 Flow description % Compressibility Excellent flow 5-15 Good 16-18 Fair 19-21 Poor 22-35 Very poor 36-40 Extremely poor >40 Relationship between powder flowability and % Compressibility
  19. Hausner ratio 3/17/2023 19 Hausner ratio was related to interparticle friction
  20. 3/17/2023 20 Hausner ratio and flow propertes Flow character Hausner ratio Excellent 1.00-1.11 Good 1.12-1.18 Fair 1.19-1.25 Passable 1.26-1.34 Poor 1.35-1.45 Very poor 1.46-1.59 Very Hauser poor >1.60
  21. The angle of repose • The maximum angle which is formed between the surface of pile of powder and horizontal surface is called the angle of repose. tan θ = h / r where, h = height of pile r = radius of base of pile 3/17/2023 21
  22. 3/17/2023 22 Angle of repose
  23. 3/17/2023 23 Angle of repose (degrees) Type of flow < 20 Excellent 20-30 Good 30-34 Passable >40 Very poor
  24. SOLUBILITY ANALYSIS 3/17/2023 24
  25. 3/17/2023 25 Solubility studies Descriptive term Parts of solvent required for 1 part of solute Very soluble <1 Freely soluble 1 to 10 soluble 10 to 30 Sparingly soluble 30 to 100 slightly solube 100 to 1000 Very slightly soluble 1000 to 10000 Practically insoluble or insoluble 10000 and over
  26. • Solubility and absorbtion can altered by changing pH • The Henderson -Hasselbach equation provides an estimate of the ionized and unionized durg concentration at a particular pH. For acidic compounds, pH = pKa + log (un-ionized drug) / [ionized drug] for basic compounds, pH = pKa + log (ionized drug) / [un-ionized drug] 3/17/2023 26 Ionization constant- pKa
  27. • For very weakly acidic drug (pKa >8) such as phenytoin and ethosuximide, or for very weakly basic drugs, (pKa<5), such as diazepam the unionized form is present throughout the GIT and there absorption is rapid. • For weakly acidic drug (pKa= 3-7), such as aspirin and ibuprofen, the unionized form is present within the acidic contents of the stomach, but the drug is ionized in intestinal media. Such drugs are better absorbed from stomach. • For weakly basic drug (pKa=5-8), such as morphine and choroquine the unionized form is present within the basic content of the intestine, but drug is ionized in acidic media of stomach. Such drug are better absorbed from intestine. • For strongly acidic drugs, such as cromolyn sodium or strongly basic drugs such as erythromycin ,the ionized form is in both the stomach and intestine. 3/17/2023 27
  28. An incompatibility in the dosage form can result in any of the following changes : 3/17/2023 28 Drug-excipient compatibility Changes in organoleptic properties Changes in dissolution performance Physical form conversion Decrease in potency An increase in degradation products
  29. • Dissolution of drug particle is controlled by following factors: 3/17/2023 29 Dissolution Dissolution Crystal habit Particle size Temperature Surface area
  30. Partition coefficient • The ratio of unionized drugs dispersed between the organic (n-octanol) and aqueous (water) phases at equilibrium is known as the partition coefficient (P). • This is helpful to predict drugs’ ability to cross cell membrane. 3/17/2023 30 Partition coefficient Partition coefficient =0 drug equally soluble in water and organic solvent Partition coefficient >1 = drug is lipophilic Partition coefficient <1 = drug is hydrophilic
  31. 3/17/2023 31 Seprating funnel
  32. Stability analysis 3/17/2023 32 The primary objective of this study is investigation and identification of stable storage condition for drug in the solid state and identification of compatible excipients for a formulation. Types of stability Conditions maintained during the shelf life of product Chemical Retains its chemical integrity and potency Physical Retains appearance, palatability Threapeutic effect Drug action remains unchanged
  33. • Preformulation study helps to develop safe, effective and stable dosage form. • Preformulation has an impact on the selection of the drug candidate, formulation components, physicochemical properties of drug. • Preformulation studies focus on the physicochemical properties of new compound that could affect the drug performance. • Preformulation study also focus on the stability and solubility of drug 3/17/2023 33 Conclusion
  34. Refrences 1. Vilegave K, Vidyasagar G, Chandankar P. Preformulation studies of pharmaceutical new drug molecule and products: an overview. The american journal of pharmacy. 2013;1(3):1-20. 2. Chaurasia G. A review on pharmaceutical preformulation studies in formulation and development of new drug molecules. International J. Of pharmaceutical science and research. 2016 june 1;7(6):2313-0 3. Hasan MM, Al Habib S, islam MM, Islam MM, Karim MS, Banik K, Rashid HA. Pharmaceutical preformulation for product development & analytical techniques use in new dosage form. International journal of pharmacy & therapeutics. 2017;8(1):16-32. 4. Leon lachman / Lieberman’s , The theory and practice of Industrial Pharmacy . Indian 4rth edition CBS publisher, reprint 2020, page no.217-251 3/17/2023 34
  35. 5. Michael E Aulton, Pharmaceutics- The design and manufacture of medicines, 3rd International edition, page no. 23-24 6. Remington, Pharmaceutics- The science and practice of pharmacy, Volume 1, 20th edition, Page no. 705. 7. D. M. Brahmankar and Sunil B. Jaiswal, Biopharmaceutics and Pharmacokinetics- a treatise, Vallabh Prakashan, Page no. 27-29. 3/17/2023 35
  36. 3/17/2023 36 Thank you