PREFORMULATION – PARTICLE SIZE

1. PREFORMULATION – PARTICLE SIZE Dr. Dinesh M. Biyani, M. Pharm. Ph.D. DBM, DIRPM, Dip TD Associate Professor, SKB College of Pharmacy, Kamptee dineshbiyani10@gmail.com

2. PREFORMULATION Preformulation testing encompasses all studies enacted on a new drug compound in order to produce useful information for subsequent formulation of a stable and Biopharmaceutically suitable dosage form AKER’S Do not neglect these foundations. Good Preformulation will inevitably lead to simple and elegant formulations and successful commercial products WELLS

3. PREFORMULATION STUDIES Physical Description Purity – Identification and Evaluation of…..properties Chemical - Structure, Form, Reactivity Physical - Physical description, Particle size (and distribution), Crystalline structure, Melting Point and Solubility Biological – Ability to get to a site of action & elicit a biological response

4. Liquids – Although seldom but important (if volatile! ) Strategies Conversion…….NTG Softgel…….vitamins, cyclosporin Solid ester/salt , capsule/tablet……scopolamine HBr Mixing with solid/melted semisolid……high m.p. PEGs

5. PREFORMULATION STUDIES Microscopic Examination Melting point depression Phase rule Particle size

6. PARTICLE SIZE Particle size affects formulation characteristics as well as absorption Dissolution rate Bioavailability Content uniformity Taste, texture, color & stability Flow characteristics & sedimentation rates Crystal growth Pulmonary delivery tabletting

7. BP AND BPC CLASSIFICATION COARSE POWDER – All particles passes through 1700 µm aperture 40% (weight) through 355 µm MODERATELY COARSE POWDER – All 710 µm 40% (weight) through 250 µm MODERATELY FINE POWDER – All 355 µm 40% (weight) through 180 µm FINE POWDER – All 180 µm 40% (weight) through 125 µm VERY FINE POWDER – All 125 µm 40% (weight) through 45 µm MICROFINE POWDER - 90% passes through 45 µm SUPERFINE POWDER - 90% by no. of particles are < 10 µm ULTRAFINE POWDER – 90% of particles have diameter 5 µm & No particle have a diameter 50 µm

8. Particle size reduction milling – ball mill and other micronization Methods to detect surface properties Dynamic vapour sorption (DVS), XRD, DSC Micro calorimetric techniques – Inverse gas chromatography (IVG)

9. PARTICLE SIZE DISTRIBUTION MEASURMENT METHOD SIZE RANGE (µm) Sieving (woven wire) 20- 1,25,000 Sieving (electroformed) 5- 120 Sieving (perforated plate) 1000- 1,25,000 Microscopy (optical) 0.5- 150 Microscopy (electron) 0.001- 5 Sedimentation (gravity) 1- 50 Sedimentation (centrifugal) 0.01- 5 Electron zone sensing (Coulter counter) 1- 200 Laser light scattering (Fraunhofer) 1- 1000 Laser light scattering (quasi electric) 0.001- 1

10. Dispersion medium plays important role in these analyses. Dispersion medium - have a suitable absorbency - not swell the particles - disperse a wide range of particles - slow sedimentation of particles - homogenous dispersion - safe and easy to use Sub micron particles – method of choice is quasi electric light scattering photon correlation spectroscopy (PCS) and single particle optical sizing (SPOS) also are good

11. COLOUR Different batch reproducibility Degradation products Subtle difference in colour due to variation in particle size distribution Qualitative – subjective perception Quantitative – tristimulus calorimetry Shelf life of formulation can be specified using Commission Internationale de’ Ecalarge (CIE)