Solubility: Concept: The maximum extent to which a drug dissolves in a solvent at a

2. Dissolution kinetics 3. pKa 4. Partition or distribution coefficient log P or log D 5. Permeability of a drug across biological membranes 6. Solution state stability 7. Solid state stability 8. Solid state properties Derived pre­formulation properties: The properties that a drug substance should have to develop a particular dosage form like solid, oral, liquid oral or parenteral are called derived properties. Derived pre­formulation properties for solid oral dosage form like tablet, include 1. Particle size 2. Bulk density 3. Flow properties 4. Compaction behavior Derived pre­formulation properties are specific to a particular dosage form to be developed. To develop capsules, compaction behavior is not required. Drug ­ Excipients interactions: The last activity in pre­formulation studies is compatibility studies; the physical and chemical stability of the drug molecule is studied in presence of excipients. The choice of excipients selected for the study depends on the type of dosage form to be developed.

1. Solubility: Concept: The maximum extent to which a drug dissolves in a solvent at a

particular temperature is called solubility. Example: Solubility of paracetamol is 1 g in 70 ml water, solubility of NaCl is 35 g in 100 ml water. 2 Sir C.R.R College of Pharmaceutical Sciences, Eluru, Andhra Pradesh, India Importance: Solubility is an important pre­formulation property that affects the performance of a drug molecule. Solubility plays an important role during formulation development. Bioavailability of tablets and capsules depend on solubility and dissolution rate of the drug. Orally administered drug has to first dissolve in gastrointestinal fluid before it can be absorbed. Dissolved drug then passes through the intestinal membrane and enters into blood. Solubility studies in non­aqueous solvents are important for development of analytical methods, crystallization method and formulation development of soluble oral or Parenteral formulations. About 40 of drug molecules fail to come into the market because of poor aqueous solubility. Determination: Solubility of a drug is determined using shake flask method. Pre­formulation solubility studies are carried out in distilled water, 0.9 NaCl isotonic solvent, 0.01 M HCl, 0.1 M HCl, 0.1 M NaOH all at room temperature and at 37 degree centigrade. Solubility studies are also carried out in fasted state simulating intestinal fluid the fed state simulated intestinal fluid. The effect of temperature and pH on solubility of drug is also studied. If a drug is having poor solubility and dissolution rate, limited solubilization experiments are carried out using co solvency micellar solubilization complexationsolid dispersions salt formation principles. This information will be useful for the formulation scientist to formulate his dosage form. Example: Diclofenac is converted into diclofenac sodium to increase its aqueous solubility and dissolution rate. Example: Nimesulide is complexed with beta cyclo dextrin to increase its aqueous solubility, dissolution rate and bio­availability.

2. Dissolution Rate: Concept: The process by which a drug goes into a solvent to form a solution is