Tiêu đề 4. Liquid orals.pdf ✅

(3.1) Chapter 3 ... LIQUID ORALS Upon completion of the chapter, students will be able to understand: • The key building blocks of liquid dosage forms. • The technologies used in preparation and evaluation of various liquid dosage forms . • The knowledge to develop liquid dosage forms with desired safety, sensory, stability and efficacy. 3.1 INTRODUCTION Liquid orals are the liquid dosage formulations containing one or more active ingredients with or without additives dissolved in a suitable vehicle, meant for oral administration. Examples of liquid orals are syrups, elixirs, linctuses, mixtures, oral drops, solutions, suspensions, emulsions etc. Here formulation of monophasic liquids is discussed. Liquid orals are the big category of formulations in the pharmaceutical dosage formulations market. 25-30% of monographs in pharmacopoeia are liquids. They are used so widely even though solid dosage formulations are dominating now-a-days because of certain advantages mentioned below. Advantages of Liquid Orals: 1. Liquid dosage formulations are preferred dosage formulations for the children who feel difficulty in swallowing solids. This is also true with elderly patients. 2. Bioavailability of liquids is more than solids, sometimes equal to that of intra muscular injections. 3. The solution is the only form in which certain compounds can be obtained. For example hydrogen peroxide solution. 4. The liquid, sometimes, is more stable and convenient than the solid compound. For example, ferric chloride solution. 5. The substance is formed by chemical interaction in solution, and as the latter is the form in which it is most frequently required, there would be no advantage gained in isolating the solid compound. For example, strong ammonium acetate solution. 6. A liquid provides a convenient form for prescribing and dispensing substances the dose of which is a small fraction of a grain. For example solution of strychnine hydrochloride. 7. Sometimes the patients expect the drug in liquid dosage formulation for certain diseases. Examples are cough syrups and antacids.
Industrial Pharmacy-I 3.2 Liquid Orals 8. Liquid dosage formulations can be made more pleasant by adding suitable colours, flavours and sweeteners, if necessary viscolizers can be added to increase the viscosity. 9. The drug is uniformly distributed, therefore, no need to shake the container. 10. Some drugs are irritating to the gastric mucosa. When given in a tablet or capsule form. This irritation may be reduced when the drug is given in solution because of the dilution factor. Disadvantages of Liquid Orals: 1. Most of the drugs are known to undergo reactions like hydrolysis, oxidation etc. Such reactions are more severe in liquids. 2. Many drugs pose problems in solubilizing them in the given solvent. Special techniques should be followed to dissolve such poorly soluble drugs. 3. Formulation of liquids, sometimes, includes more number of steps than solids. 4. Liquids are stored in the containers which create problems like sorption, leaching, air permeability etc. 5. It is difficult to mask unpleasant flavours. 6. The bulk and weight of dosage form are high. 7. Contents are vulnerable loss by breakage of the container. 8. Patient is instructed to measure the dose. Hence drug administered depends on the measurer and accuracy of the patient. 9. Liquids are more prone to bacterial contamination. 10. The pleasant taste of liquid formulations may result in overdosage. This is especially hazardous with children. Preformulation of Liquid Orals: A successful liquid oral is one that is developed to satisfy the ideal requirements of stability, therapeutic effectiveness, and pleasing appearance. The knowledge of the factors influencing the manufacture of liquid orals is essential to solve the formulation problems. 3.2 SOLUBILITY In the preparation of liquids the drug is dissolved in the solvent of intended use. But the dissolution of drug depends on; • Nature of solvent • Nature of solute • Intensity of the forces present in solute-solvent • Solute-solvent interactions • Steric factors • Electronic factors
Industrial Pharmacy-I 3.3 Liquid Orals Determination of Solubility: Before attempting to formulate a solution the solubilities of any ingredients must be determined. This can be done by placing an excess of finely divided drug in a tightly closed container along with the solvent. This container is then agitated at constant temperature bath for 72 hours. Samples are withdrawn to determine the solubility of the drug by suitable analytical technique. Factors Influencing Solubility: 1. pH: Most of the drugs are either weak acids or weak bases. They are insoluble or slightly soluble in water while their salts are soluble. The solubility of these agents is markedly influenced by pH of their environment. The values for the solubility constant Ks and the dissociation constants Ka or Kb that are reported in the literature are usually for the drug in distilled water. These values are not always helpful as such. Because these values differ for the dosage formulation like elixir containing more amount of solid and cosolvents. In general, cosolvents such as alcohol or glycerin have the effect of increasing solubility constant and decreasing the dissociation constant. The drug’s pH environment should be fixed by keeping certain points in mind. • The solvent used for the dosage formulation. • The concentration of the drug required in the formulation. • pH should not decrease the stability of the product. • pH should encourage physiologic compatibility. During the formulation of solutions of acidic and basic drugs, the following factors must be considered. • The solubility of ionized and unionized forms of the drug. • The chemical stability of the drug as functions of the pH and the buffer components. • The therapeutic or pharmaceutical efficacy of the drug. The buffer pH and buffer type are selected to maintain a proper balance between these three variables. 2. Buffers: After fixing pH of the drug’s environment, the formulation must be supplied in such a way as to maintain the pH throughout its life. But in certain cases there is a possibility of change in the pH. To avoid consequences of pH change, suitable buffers must be added. The selection of a buffer must be consistent with the following criteria: • The buffer must have adequate capacity in the desired pH range. • The buffer must be biologically safe for the intended use. • The buffer should have little or no deleterious effect on the stability of the final product. • The buffer should permit acceptable flavouring and colouring of the product. • The pKa of the acid used in buffer should be close to the desired pH of the final dosage form.