Pharmaceutics I (PT 303) Liquid Dosage Forms Lecture 1 PDF

Pharmaceutics I (PT 303) Liquid dosage forms lecture 1 Solutions Dr. Al Zahraa Gamil Al Ashmawy Lecturer of pharmaceutics and pharmaceutical technology Email: [email protected]  Aim of the course This course...

Pharmaceutics I (PT 303) Liquid dosage forms lecture 1 Solutions Dr. Al Zahraa Gamil Al Ashmawy Lecturer of pharmaceutics and pharmaceutical technology Email: [email protected]  Aim of the course This course is a study of the system of weights, measures, mathematical expertise and pharmaceutical calculations requisite to the compounding, dispensing, and utilization of drugs in pharmacy practice. It is also concerned with all manufacturing formulations aspects, packaging, storage and stability of liquid dosage forms including solutions (aqueous and non-aqueous), suspensions, emulsions and colloids with emphasis on the technology and pharmaceutical rationale fundamental to their design and development. The incompatibilities occurring during dispensing are also considered. Course Learning Outcomes: 1. List the different types of solutions, colloids, suspensions and emulsions. 2. Recall excipients required for preparation of solutions. colloids, suspensions and emulsions and their role in formulation. 3. Utilize the pharmaceutical abbreviations properly. 4. Illustrate the procedures and techniques used to prepare solutions, colloids, suspensions and emulsions. 5. Distinguish different incompatibilities occurring during preparation and dispensing of liquid dosage form. 6. Apply pharmaceutical calculations necessary for formulation of liquid dosage forms. 7. Utilize properly suitable glassware for preparation of liquid dosage forms. 8. Utilize chemicals properly for preparation of liquid dosage forms according to safety regulations. 9. Justify time management skills. 10. Solve problems encountered during formulation of liquid dosage forms. Weighting of Assessments Final Written Examination 50 % Oral Examination 10 % Practical Exam 25 % Semester Work (Quizzes & Assignment)15 % Total 100 %  Liquid Dosage Forms 1. Monophasic Aqueous and non-aqueous solutions 2. Polyphasic Colloids Suspensions Emulsions  Liquid Dosage Forms 1. Solutions (Molecular dispersion): Clear liquid preparations containing one or more active ingredients dissolved in a suitable vehicle. 2. Colloids (Colloidal dispersion): A system in which finely divided particles, which are approximately less than 1 µm in size, are dispersed within a continuous medium in a manner that prevents them from being filtered easily or settled rapidly. 3. Suspensions (Solid in liquid dispersion): Liquid preparations containing one or more active ingredients suspended in a suitable vehicle. 4. Emulsions (Liquid in liquid dispersion): Usually two phase system in which one liquid is dispersed throughout another liquid in the form of small particles.  Emulsion https://www.youtube.com/watch?v=XEAiLm2zuvc Let’s see this video https://www.youtube.com/watch?v=i4lTvRNkRP4 Give the scientific term: Clear liquid preparations containing one or more active ingredients dissolved in a suitable vehicle. (Solutions)  Pharmaceutical solutions Solution is a homogenous mixture composed of two or more substances. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvents are aqueous or non aqueous. A common example is a solid, such as salt or sugar, dissolved in a liquid, such as water.  Classification of solutions 1. Classification of the solutions according to pharmaceutical use (route of administration):  An oral solution : (ingested) through oral route  Otic solution : (instilled in the ears)  Ophthalmic solution: (instilled into the eye)  Nasal solution: (instilled into the nose)  Topical solution: applied over skin surface  Rectal and vaginal solutions (enema and douche) 2. Classification of the solutions according to their composition 1. Syrups: aqueous solutions containing a sugar. 2. Elixirs: sweetened (sugar) hydroalcoholic (combinations of water and ethanol). 3. Spirits: alcoholic or hydroalcholic solution of volatile substance. 4. Tinctures: are alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical substances. 3. Classification of the solutions according to solvent (Vehicle) used Aqueous solutions -Solutions that contain water as the solvent. e.g. sugar in water, carbon dioxide in water, etc. Non-aqueous solutions - Solutions that contain a solvent other than water. e.g., ether, benzene. e.g. naphthalene in benzene.  Advantages of solutions Disadvantages of solutions 1. Easy to swallow for young children and some 1. Unpleasant taste or odor is difficult to mask adults especially elderly who have difficulty in swallowing tablets and capsules. 2. They give more rapid action than tablets and 2. They are bulky to carry around. capsules (solutions> suspensions> capsules> tablets). 3. They give uniform dose than suspension due 3. It needs an accurate measuring device to to homogeneous distribution of medicament get the correct dose. throughout the solution, no need for shaking 4. They dilute the irritant action of some drugs 4. Drugs in aqueous solution are poorly stable (e.g., KCl and aspirin). rather than if they were formulated as a tablet or capsule. 5. Suitable medium for the growth of M.O.  Easy to swallow Poorly stable Uniform dose than suspension Unpleasant taste or odor Give more rapid action Bulky Growth of M.O Accurate Dilute the irritant action measuring of some drugs device Solutions are classified according to the type of solvent used: 1. Aqueous solvents 2. Non-aqueous solvents  1. Aqueous solvents Water is the most widely used solvent for use as a vehicle for pharmaceutical products due to: 1. Lack of toxicity. 2. Physiological compatibility. 3. Ability to dissolve a wide range of materials.  Types of water Tap water Purified water  Tap water Purified water Is suitable for drinking. Has fewer solid impurities than ordinary It contains dissolved inorganic salts (e.g Na, K, Ca, Mg) drinking water, (1mg of solid per 100 ml of along with dissolved and undissolved organic matter and water) microorganisms (100 mg of solids per 100 ml of water). It’s use is permitted in washing, in extraction of crude Used for preparation of aqueous dosage vegetable drugs, or in the preparation of certain forms, except those intended for parenteral products for external use. administration (injections). Is not acceptable for the manufacture of most aqueous Water for Injection, Sterile Water for pharmaceutical preparations because of possible chemical Injection are used. which need highly pure, incompatibilities between dissolved solids and the sterile and pyrogen free water medicinal agents added. Signs of such incompatibilities are precipitation, discoloration and effervescence. The methods of preparation of purified water 1. Distillation 2. Ion exchange 3. Reverse osmosis 1. Distillation Simple distillation can be carried out in flasks equipped with condensers. Water is heated to boiling. Generated water vapor is allowed to pass through the condenser and return to liquid state, leaving behind salts in the distillation flask. The first amount of distillate is discarded as it contains foreign volatile substances usually found in drinking water. The last amount of distillate is discarded as it contains heavy metals. Distilled water is not sterile. https://www.youtube.com/watch?v=V5ep0-ojPGw https://www.youtube.com/watch?v=7Ax5B2veHUo 2. Ion exchange The resins are mainly of two types: a. The cation, or acid exchangers which permit the exchange of the cations in water with hydrogen ion from the resin. H-resin + M+ + X- + H2O ՜ M-resin + H+ + X- + H2O (Pure) b. The anion, or base exchangers which permit the removal of anions from water. Resin-NH2+ H+ + X- + H2O- ՜ Resin-NH2. HX + H2O(Pure) or [Resin-NH3+.X-]  These two processes are successively employed to remove both cations and anions from water.  Advantages of ion exchange 1. No heat is required 2. Ease of operation 3. Simple equipment It is possible to remove ions from water through the use of ion exchange resins. 3. Reverse osmosis A pressurized stream of water is passed parallel to the inner side of a filter membrane core. A portion of the feed water, permeates the membrane as filtrate, while the rest of water exits the system without being filtered. The filtered portion is called the “permeate" because it has permeated the membrane. The water that has passed through the system is called the "concentrate" because it contains the concentrated contaminants rejected by the membrane.  Solubility Definition:- the maximum amount of solute that can be dissolved in a certain volume of solvent at a given temperature. When a solvent at a given temperature, has dissolved all of the solute it can, it is said to be saturated. Attractive forces between atoms leads to the formation of molecules and ions. These forces includes vander wal forces, ion dipole and ion-induced dipole forces) and hydrogen bonding,  Explanation for solubility Three types of interactions are considered in the solution process: solvent-solvent interaction, solute-solute interaction and solvent-solute interaction. Consider the solution process taking place in three distinct steps 1. Separation of solvent molecules 2. Separation of solute molecules 3. Mixing of solvent and solute molecules In the process of making solutions, intermolecular forces become rearranged.  Factors affecting the solubility 1. Temperature is an important factor in determining the solubility of a drug and in preparing its solution. Most chemicals absorb heat when they are dissolved and are said to have a positive heat of solution, resulting in increased solubility with an increase in temperature. (Endothermic solubility) A few chemicals have a negative heat of solution and exhibit decrease in solubility with a rise in temperature. (Exothermic solubility) 2. Chemical and physical properties of both the solute and solvent 3. Pressure. 4. pH of the solution. 5. The physical agitation applied to the solution during the solubility process. Approaches to the improvement of aqueous solubility 1. Co-solvency 2. pH control 3. Solubilization 4. Complexation 5. Chemical modification 6. Particle size control 1. Co-solvency The addition of a water-miscible solvent to increase the solubility of a weak electrolyte or non-polar compound in water is called “Co solvency”. The solvents used in combination to increase the solubility are called “Co solvents". Suitable blends should possess dielectric constant between 25& 80. Examples of Co-solvents: Water / ethanol blend, also other suitable solvents are sorbitol, glycerol, & propylene glycol. Examples of Co-solvency: A blend of propylene glycol and water is used to improve the solubility of co-trimoxazole (Antibiotic).  2. pH control The solubility of a weak base is at low pH of solution. The Solubility of a weak acid is at high pH of solution. e.g: 1.Chemical stability of a drug: It depends on pH so sometimes the pH of optimum solubility does not coincide with the pH of optimum stability. 2. The pH of solutions for parenteral & ophthalmic use: It must also be controlled as extremes can cause pain and irritation. 3. Preservative activity: Is affected due to altering the degree of its ionization. 4. Concentration of co solvent : The inclusion of co solvents i.e. alcohol or propylene glycol will lower the dielectric constant of the vehicle so increase the solubility of unionized form of the drug. 3. Solubilization The solubility of a drug (insoluble or poorly soluble in water) can be improved by the addition of a surface active agent (SAA). Properties of SAA used: 1. Possessing HLB values >15. 2. It must be non-toxic, non volatile & non-irritant. 3. It must also be miscible with the solvent, compatible with other ingredients, 4. free from disagreeable odor,taste. Examples:  Solubilization of fat-soluble vitamins using polysorbates (Tweens). 4. Complexation It is the interaction of a poorly soluble drug with a soluble material to form a soluble “intermolecular complex” The term "hydrotropy", is defined as the increase in aqueous solubility of a material by the inclusion of additives. Examples of water-soluble complexes: Complexation of iodine with 10-15 % solution of polyvinyl pyrrolidone (PVP) [BETADINE]. 5. Chemical modification It is the production of a water soluble derivative of the drug. Example:  The water soluble chloramphenicol sodium succinate has no antibacterial activity of its own but is suitable for parenteral administration as a solution (conversion to the active base). 6. Particle size control As particle size decreases, the surface area increases and the solubility will increase. 2. non-aqueous solvents Advantages of using non-aqueous systems: Difficulty in solubility or unstability of drugs in aqueous systems. Depot Therapy: Intramuscular injection of solutions of drugs in oils remains as a discrete entity within the muscle tissue, releasing the drug slowly. Points of consideration when choosing a suitable non-aqueous solvent: Toxicity, irritancy, Sensitizing potential. Flammability Cost Stability Compatibility with other excipients. Some solvents for liquid preparations 1- Alcohol, USP (Ethyl Alcohol, Ethanol( Next to water, Alcohol is the most useful solvent in pharmacy. It is used as a primary solvent for many organic compounds. Together with water it forms a hydroalcoholic mixture that dissolves both alcohol-soluble and water-soluble substances and it is useful in the extraction of active constituents from crude drugs. By varying the proportion of two agents (water and alcohol), the active constituents may be selectively dissolved and extracted. Alcohol, USP, is 94.9 to 96.0% C2H5OH v/v. Dehydrated Alcohol, USP, contains not less than 99.5 % C2H5OH by volume. Advantages: 1. Miscibility with water. 2. Ability to dissolve many water- insoluble ingredients, drugs, flavorants & antimicrobial preservatives. 3. Used as preservative alone or with parabens, benzoates. Disadvantages: 1. Undesired pharmacologic effects. Oral use 2. Potential toxic effects. Content limit (FDA): 1. 0.5% for OTC oral products intended for children 12 years. 2- Diluted Alcohol Mixing equal volumes of Alcohol and Purified Water. The final volume of such mixtures is not the sum of the individual volumes of the two components, because the liquids contract upon mixing. The final volume is generally 3% less than what would be expected. Then, 50 ml water + 50 ml alcohol = or measures approx. 97 ml 3- Alcohol, Rubbing Rubbing Alcohol contains about 70 % of ethyl alcohol by volume, the remainder consisting of water, denaturants with or without color additives, perfume oils, and stabilizers. 4- Isopropyl Rubbing Alcohol It is about 70 % by volume isopropyl alcohol, the remainder is water with or without color additives, stabilizers and perfume oils. It is used externally as a rubefacient (stimulating blood flow to rubbed area) and as a vehicle (carrier in which substance is dissolved) for topical products. It is commercially available as 91% v/v and used by diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin. 5- Glycerin, USP (Glycerol), CH20H.CHOH.CH20H Glycerin is a clear viscous liquid with a sweet taste. It is miscible both with water and alcohol. As a solvent, it is comparable with alcohol, but because of its viscosity, solutes are slowly soluble in it unless it is rendered less viscous by heating. Glycerin has preservative qualities. 6- Propylene Glycol It is a viscous liquid, miscible with water and alcohol. It is a commonly used drug solubilizer in topical, oral, and injectable medications. It is also used as stabilizer for vitamins, and as a water- miscible cosolvent. 7- Fixed oils of vegetable origin  These are non-volatile oils which consist mainly of fatty acid esters of glycerol Examples:  Olive oil, sesame oil, maize oil, cotton seed oil, soya oil & castor oil, are suitable for parenteral use.  Almond oil (glycerides mainly of oleic acid), solvent for oily phenol injection (caustic nature of aqueous phenol solutions).  Some fixed oils are tasteless & odorless which is suitable for oral use. (i.e. solvents for compounds as vitamins (A) & (D) ). 8. Liquid paraffin It is used as a solvent for the topical application of drugs in emulsion formulations (*unpleasant oily nature). Internally, it is indigestible & absorbed only to a limited extent, it is used as an emollient cathartic in the form of emulsion.