1. In order to enter the systemic circulation to exert therapeutic effect, it must first be in solution. So, the drug must posses some aqueous solubility for therapeutic efficacy.
2. Purity
2.1. Is another testing parameter for comparison with subsequent batches
2.2. It's necessary to detect the purity or homogeneity of the drug substance as
2.2.1. Affect stability
2.2.2. Affect appearance
2.2.3. Shift the optimum wavelength for determination of conc.of the main component
2.2.4. May be toxic, carcinogenic
2.3. Techniques for detecting purity of medicinal substance
2.3.1. TLC
2.3.1.1. USP impurity index
2.3.1.1.1. Ratio of responses due to impurities to that response due to a defined conc.of a standard of the main component
2.3.2. HPLC
2.3.2.1. Impurity index II
2.3.2.1.1. Is the ratio of responses due to components other than the main one to the total response
2.3.2.2. Homogeneity index HI
2.3.2.2.1. Is the ratio of responses due to the main component to the total response
2.3.3. GC
2.3.4. Differential scanning calorimetry
2.3.5. Melting point depression
2.3.5.1. Melting point is the temperature at which the pure liquid and solid exist in equilibrium
2.3.5.2. Molar heat of fusion
2.3.5.2.1. Is the quantity of heat absorbed when one mole of solid melt
2.3.6. Phase solubility analysis
3. Flow, cohesiveness, compressibility
3.1. Factors affecting the flow of the powder
3.1.1. Density
3.1.2. Particle size
3.1.3. Shape
3.1.4. Electrostatic charge
3.1.5. Absorbed moisture
3.2. Reasons for good powder flow
3.2.1. Uniform feeding
3.2.2. Reproducible filling of tablet
3.2.3. Uneven powder result in excess entrapment of air do cause capping and lamination
3.3. Determination of powder flow properties
3.3.1. Angle of repose
3.3.2. Bulk density measurements
3.4. To improve flowability
3.4.1. Reduce electrostatic charge by Mg stearate and silicon dioxide
3.4.2. Remove fine powder by granulation
3.4.3. Using glidant to reduce adhesion and cohesion
3.4.4. Reduce moisture by Mg oxide
4. Ionization constant(pKa)
4.1. Is the pH at which the ionized and unionized form of the drug exist in equilibrium
5. Solubility
5.1. Aqueous solubility
5.2. Determination of solubility
5.2.1. By equilibrium solubility method
5.2.1.1. By employing a saturated solution of the substance, obtained by stirring an excess of material in the solvent at constant temperature until equilibrium achieved
5.2.1.2. Solubility ideally measured at two temperatures:4°C and 37°C
5.3. Intrinsic solubility
5.3.1. Is the fundamental solubility of the substance when completely unionized
6. Dissolution
6.1. Is a process in which a solid substance solubilizes in a given solvent
6.2. Dissolution rate
6.2.1. Is the amount of drug substance that goes in solution per unit time under standardized conditions
6.2.2. Factors affecting dissolution rate
6.2.2.1. Physicochemical properties of drug
6.2.2.2. Drug product formulation factors
6.2.2.3. Processing factors
6.2.2.3.1. Method of granulation
6.2.2.3.2. Compression force
6.2.2.3.3. Drug excipient interaction
6.2.2.4. Factors relating to dissolution apparatus and parameters
6.2.2.4.1. Agitation
6.2.2.4.2. Temperature
6.2.2.4.3. Dissolution medium
6.3. Intrinsic dissolution rate
6.3.1. Is the dissolution rate under the condition of constant surface area
7. They should be stored in a well closed container preferably with a Desiccant
8. Organoleptic properties
8.1. Are those properties which are evaluated after impression on the organs of sense
8.2. As
8.2.1. Color
8.2.2. Odor
8.2.3. Taste
9. Hygroscopicity
9.1. Is the measurement of the material ability to absorb or release water as a function of humidity
9.2. Materials can be
9.2.1. Hygroscopic
9.2.1.1. Material which are in dynamic equilibrium with water in the atmosphere
9.2.2. Deliquescent
9.2.2.1. A substance that absorb sufficient moisture from the atmosphere to dissolve itself
9.2.3. Efflorescent
9.2.3.1. A substance that loses water to form a lower hydrate or become anhydrous
9.3. Precautions for formulating and storage of hygroscopic compound
9.3.1. Non aqueous granulating solvent are used for granulation
10. Particle size
10.1. It is essential to establish as early as possible how the particle size of the drug substance may affect formulation and product efficacy
10.2. Methods of determination of particle size
10.2.1. Optical microscopy
10.2.1.1. Slow, tedious as it must measure at least 300_500 particle
10.2.1.2. Size is expressed as projected diameter
10.2.2. Sieving
10.2.2.1. Size is expressed as sieve diameter
10.2.2.2. Inexpensive, simple and rapid
10.2.3. Sedimentation
10.2.3.1. Size is expressed as stock diameter
10.2.4. Coulter counter
10.2.4.1. Size is expressed as volume diameter
10.2.5. Determination of surface area
10.2.6. Zetasizer
10.2.6.1. Particle size is determined by reduction in light reaching the sensor and scattering of incident laser light by particle dispersed in a liquid or gas, passes through the sensing zone
10.2.7. Scanning electron microscope
11. Partition coefficient
11.1. Is the measurement of a drug lipophilicity and it's ability to cross cell membrane
12. Polymorphism
12.1. Is the ability of the compound to exist as two or more crystalline phases that have different arrangements of the molecules in the crystal lattice
12.2. Polymorph are 2 Types
12.2.1. Enantiotropic
12.2.2. Monotropic
12.3. Pseudopolymorph or solvates
12.3.1. It is the incorporation of solvent molecule into crystal lattice of solid
12.4. Differentiation between pseudopolymorph and true polymorph
12.4.1. By hot stage microscopy