Ceutics Lec 1 PDF

Advantages of solutions as an oral dosage form:  Liquids are easier to swallow, so they are preferred for pediatric and geriatric use.  Drugs administered in the form of a solution are immediately available for absorption.  Solutions are homogenous systems i.e the drug is unif...

Advantages of solutions as an oral dosage form:  Liquids are easier to swallow, so they are preferred for pediatric and geriatric use.  Drugs administered in the form of a solution are immediately available for absorption.  Solutions are homogenous systems i.e the drug is uniformly distributed throughout the preparation.  Irritation is reduced by administration of a solution of a drug due to the immediate dilution by the gastric contents. Disadvantages of solutions as an oral dosage form: 1. Liquids are bulky to transport and store. 2. Poor stability of ingredients in aqueous solutions. 3. Solutions often provide suitable media for the growth of M.O. and may therefore require the incorporation of a preservative. 4. The taste of a drug, is always more pronounced when in solution. Solutions can, however, easily be sweetened and flavored to make them more palatable. 5. Accurate dosage usually depends on the ability of the patient to use a spoon or, a volumetric dropper.  Definition  In pharmaceutical terms , solutions are liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of mutually miscible solvents. Solubility  Solubility  The maximum concentration of solute to which a solution may be prepared with that agent and that solvent. When a solvent at ,a given temperature , has dissolved all of the solute it can , it is said to saturated.  When a solute dissolves , the substance’s intermolecular forces of attraction must be overcome by forces of attraction between the solute and solvent molecules.  Solubility This involves breaking the solute –solute forces and the solvent – solvent forces to achieve the solute-solvent attraction.  Prediction of solubility  “like dissolves like,”  a solvent having a chemical structure most similar to that of the intended solute will be most likely to dissolve it.  Strong electrolytes (ionizable) and polar compounds are soluble in water.  Organic compounds are more soluble in organic solvents than in water.  Factors affecting solubility 1- Temperature: Most chemicals absorb heat when they are dissolved and are said to have a positive heat of solution increased solubility with an increase in temperature. A few chemicals have a negative heat of solution and exhibit a decrease in solubility with a rise in temperature. 2- pH of the solution: Many of the important organic medicinal agents are either weak acids or weak bases.  The solubility of a weak base (e.g. alkaloids , antihistamines, local anaesthetics) can be increased by lowering the pH of its solution. The Solubility of a weak acid (e.g. barbiturates and phenobarbital) is improved by a pH increase. 3- Rate of solution  the speed at which it dissolves, depends on: 1. The particle size of the substance  The finer the powder  the greater the surface area, which comes in contact with the solvent  the more rapid the dissolving process 2. The extent of agitation  the greater the agitation, the more unsaturated solvent passes over the drug and the faster the formation of the solution. Approaches to the improvement of aqueous solubility  1. Co-solvency: Used for: weak electrolyte or non-polar compound Solubility  by: addition of a water- miscible solvent in which the compound is also soluble. Vehicles used in combination to increase the solubility are called "co solvents".  2. pH control: Used for: weak acid or a weak base Solubility  by:  The solubility of a weak base can be increased by lowering the pH of its solution.  The Solubility of a weak acid is improved by a pH increase.  3. Solubilization: Used for: Insoluble or poorly soluble drug in water Solubility  by:  Addition of a surface active agent This phenomenon of micellar solubilization has been widely used for the formulation of solutions. Solubilisation begins at Critical Micelles Concentration (CMC) It is the lowest concentration of surfactant at which micelles begin to form.  4. Complexation: Used for: Poorly soluble drug Solubility  by:  Interaction of a poorly soluble drug with a soluble material to form a soluble intermolecular complex.  E.g. Complexation with cyclodextrins  5. Chemical modification:  It’s the production of water soluble derivative of drug (e.g. water soluble salt)  Examples: 1. Synthesis of the sodium phosphate salts of hydrocortisone, prednisolone and betamethasone. 2. Water soluble chloramphenicol sodium succinate has no antibacterial activity but it is suitable for parenteral administration as a solution in order to obtain high blood levels. Then it is converted back to the active base.