objective, goal, Physical properties, polymorphism, particle size shape surface, flow properties, solubility, pKa, pH

1. Preformulation Studies Part 1
By
Dr Mrs Shruti Rathore
Professor and Principal
LCIT School of Pharmacy
Bilaspur CG

9. Product must be – good in
appearance
color must be appealing/attractive
to eye
taste and odor must be good or
overcome by using appropriate
flavor and sweeteners

10. Physical Properties

37. After 2 mints sample will be taken from 100mm height by Anderson’s
pipette. Keep assembly at constant temp.

38. Sample withdrawn
Sample added to a dish
Dried in oven

45. Particle surface area measurement
Brunauer, Emette and Teller (BET) nitrogen
adsorption method.
A layer of nitrogen molecules is adsorbed to the
sample surface at -190°C. Once surface is
saturated, the sample is heated to room
temperature, the nitrogen gas is desorbed, and its
volume is measured and converted to the number
of adsorbed molecules via gas Law. Since each
N2 molecule occupies an area of 16A2, one can
easily determine the surface area.

46. Characterization of Particle surface
morphology
The scanning electron microscope creates magnified images by
using electrons instead of light waves. The images are black and
white.

49. Angle of Repose
When bulk granular materials are poured onto a horizontal surface, a conical pile will
form. The internal angle between the surface of the pile and the horizontal surface is
known as the angle of repose and is related to the density, surface area and shapes of
the particles, and the coefficient of friction of the material. Material with a low angle of
repose forms flatter piles than material with a high angle of repose.

51. Fixed Funnel Method
The material is poured through a funnel to form a cone. The tip of the funnel
should be held close to the growing cone and slowly raised as the pile grows, to
minimize the impact of falling particles. Stop pouring the material when the pile
reaches a predetermined height or the base a predetermined width. Rather than
attempt to measure the angle of the resulting cone directly, divide the height by
half the width of the base of the cone. The inverse tangent of this ratio is the
angle of repose.

55. The Hausner ratio is a number that is correlated to the flowability
of a powder or granular material. It is named after the engineer Henry H.
Hausner (1900–1995).[
The Hausner ratio is calculated by the formula
where p bulk is the freely settled bulk density of the powder, and p tapped
is the tapped bulk density of the powder. The Hausner ratio is not an
absolute property of a material; its value can vary depending on the
methodology used to determine it.
The Hausner ratio is used in a wide variety of industries as an indication
of the flowability of a powder. A Hausner ratio greater than 1.25 is
considered to be an indication of poor flowability. The Hausner ratio (H)
is related to the Carr index (C), another indication of flowability, by the
formula .

58. •An important Physical-Chemical property of drug especially aqueous
solubility.
•A drug must possess some aq solubility for therapeutic effect between
pH range 1 to 8.
•Drug must first convert in solution form so solubility is require – if it is
less than considerable – so it must be increased.
•Insoluble compounds exhibit incomplete absorption.
•Breaking of solute-solute force and solvent-solvent forces has to be
overcome by solute-solvent forces.
•Drugs with an aqueous solubility less than 1% (10mg/ml) will suffer from
bio absorption problems.

62. pKa – Dissociation constant of drug
•Many drugs are either weakly acidic or basic compounds.
•In solution, depending on pH it is either ionized or unionized
species.
•The unionized species are more lipid soluble and more readily
absorbed.
•The git absorption of weakly basic or acidic drug – to that fraction of
drug in solution that is unionized.
•The factors important to consider for such drugs are
•pH at the site of absorption
•the ionization constant
•lipid solubility of unionized drug

63. These factors together constitute – pH partition theory.
The relative concentration ionized and unionized forms of weakly acidic
and basic drug can be calculated by Henderson-Hasselbalch equations:
For Acids,
Weakly acidic compounds having pKa value 4.3 are absorbed relatively
rapidly.
Those having pKa value range between 2.0 to 4.3 are absorbed slowly.
Strong acidic compounds having pKa value less than 2.4 get hardly
absorbed.

64. For bases,
Weakly basic compounds having pKa value smaller than 8.5
are absorbed relatively rapidly.
Those having pKa value range between 9 to 12 are
absorbed more slowly.
Ionized bases cannot absorbed.
Absorption, elimination and distribution depends on
ionization of drug.
The extent of pKa is highly dependent on pH.

66. If the drug substance is acidic or basic, its solubility can
be influence by pH.
Through the application of Law of Mass Action, the
solubility of weakly acidic or basic drug substance can
be predicted as a function of pH with a considerable
degree of accuracy.
Using following equation for weakly acidic or basic
drugs :