Pharmaceutical Solutions - Part 1 PDF

PHARMACEUTICAL SOLUTIONS DR.SHERY JACOB 1 Learning objectives After completion of this topic, the student will be able to ▪ Define and classify pharmaceutical solution dosage form ▪ Define solubility and describe how different factors increase or decrease solute...

PHARMACEUTICAL SOLUTIONS DR.SHERY JACOB 1 Learning objectives After completion of this topic, the student will be able to ▪ Define and classify pharmaceutical solution dosage form ▪ Define solubility and describe how different factors increase or decrease solute solubility in a given solvent ▪ Evaluate and select an appropriate solvent for a given solute, purpose, and/or patient population 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". According to USP42/NF37 pharmaceutical solutions are “Liquid preparations, intended for oral administration, that contain one or more substances with or without flavoring, sweetening, or coloring agents dissolved in water or co-solvent water mixtures”.  Classification  Solutions can be classified based on their use: 1. Oral solution; 2. Otic solution; 3. Ophthalmic solution; 4. Topical solution; 5. Injection (parenteral) solution. Solubility Expression Solubility may be expressed as grams of solute dissolving in milliliters of solvent. For e.g.,“1 g of sodium chloride dissolves in 2.8 mL of water.” When the exact solubility has not been determined, general expressions of relative solubility may be used. These terms are defined in the USP and presented in Table 1. DESCRIPTIVE TERMS PARTS OF SOLVENT REQUIRED FOR 1 PART OF SOLUTE Very soluble 10000 8  Factors Affecting Solubility  Temperature  Chemical and physical properties of solute and solvent  Pressure  pH  Particle size  Agitation Drugs Weak acids Weak base Salts Weak bases like codeine,morphine,atropine are not very water soluble, but they are soluble in dilute solutions of acids to form salts e.g., morphine HCl Weak acids like barbiturate drugs (e.g.,phenobarbital) are not very water soluble, but they are soluble in dilute solutions of bases to form salts e.g.,Phenobarbitone sodium Solvents For Liquid Preparations ▪ Alcohol ▪ Glycerin ▪ Propylene glycol ▪ Isopropyl alcohol ▪ Water ▪ Fixed oils ▪ Liquid paraffin Alcohol,USP;Ethyl Alcohol,Ethanol, C2H5OH 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. Used for extraction of active constituents from crude drugs. Alcohol,USP,is 94.9% to 96.0% C2H5OH by volume (v/v) when determined at I5.56C Dehydrated Alcohol, USP Dehydrated Alcohol,USP,contains not less than 99.5% C2H5OH by volume and is used when an essentially water-free alcohol is desired. For over-the-counter (OTC) oral products intended for children under 6 years of age, the recommended alcohol content limit is 0.5% Children 6 to 12 years of age-recommended limit is 5% Over 12 years and adults-recommended limit is 10% Diluted Alcohol,NF Prepared by mixing equal volumes of Alcohol,USP,and Purified water,USP It is a useful hydroalcoholic solvent in various pharmaceutical processes and preparations.  Rubbing Alcohol  It contains about 70% ethyl alcohol by volume  It contains not less than 355 mg of sucrose octa-acetate or 1.4 mg of denatonium benzoate,bitter substances that discourage accidental or abusive oral ingestion.  Volatile and flammable  Employed as a rubefacient externally and as a soothing rub for bedridden patients,a germicide for instruments,and a skin cleanser prior to injection.  Vehicle for topical preparations Glycerin, USP (Glycerol),CH2OH-CHOH-CH2 OH Glycerin is a clear syrupy liquid with a sweet taste. It is miscible with both water and alcohol. Because of its viscosity, solutes are slowly soluble in it It has preservative qualities Used as stabilizer and cosolvents Used in many internal preparation Isopropyl rubbing alcohol Contains 70% by volume isopropyl alcohol Used as a rubefacient externally and as a soothing rub Vehicle for topical products Used in diabetic patients in preparing needles and syringes for hypodermic injections of insulin and for disinfecting the skin Propylene glycol,USP,CH3CH(OH)CH2OH It is a viscous liquid miscible with water and alcohol Useful solvents with wide range of applications Frequently substituted for glycerin in modern pharmaceutical formulations Purified water,USP H2O  Purified water,USP,is obtained by distillation, ion exchange treatment,reverse osmosis,or other suitable process.  When evaporated to dryness,it must not yield more than 0.001% of residue (1 mg of solids per 100 mL water)  Purified water,USP,is intended for use in the preparation of aqueous dosage forms except those intended for parenteral administration (injections).  Water for injection,USP;Bacteriostatic water for injection,USP;or Sterile Water for Injection,USP,is used for injections. Pyrogens Water used in parenteral,ophthalmic and irrigating sols should be free of pyrogens. Pyrogens are products of metabolism of microorganisms. The fever response to pyrogens in rabbits is the basis for the official pyrogen tests. Recently,an in vitro test method (LAL Test-Limulus Amebocyte Lysate Test) for pyrogens has been developed utilizing the gelling property of the Lysate of the Amebocytes of Limulus polyphemus (the horseshoe crab) within 60 min, when incubated at 37C.  Oral solutions and Preparations for Oral Solution Most solutions intended for oral administration contain flavourants and colorants to make the medication more attractive and palatable. Stabilizers:To maintain chemical and physical stability of medicinal agents Preservatives:To prevent the growth of microorganisms in the solution (e.g.,esters of p-hydroxybenzoic acid like methyl, ethyl, propyl and butylparabens) Dry Mixtures for Solution A number of medicinal agents,particularly certain antibiotics e.g.,pencillin V, have insufficient stability in aqueous solutions to meet extended shelf-life periods. Therefore,they are avaialble as dry powders mixtures. It contain all the formulative components, including drug, flavorant, colorant, buffers and others, except for the solvent. Once reconstituted by the pharmacist, the solution remains stable for 7-14 days. E.g.,Cloxacillin Sodium for Oral Solution,USP-an anti-infective antibiotic Pencillin V Potassium for Oral Solution,USP,an anti-infective antibiotic Potassium chloride for Oral Solution,USP,a potassium supplement Stavudine for Oral Solution,USP,antiretroviral medication -HIV/AIDS 24 25  Oral Rehydrating Solutions (ORS) Rapid fluid loss associated with diarrhea can lead to dehydration and untimely death in some patients, particularly infants. Oral rehydration solutions are usually effective in treatment of patients with mild volume depletion,5%-10% of body weight. These are available OTC and are relatively inexpensive. A liter of typical oral rehydration solution contains 45 mEq Na+,20 mEq K+,35 mEq Cl-,30 mEq citrate,and 25 g dextrose. It is available in liquid or powder packet form for reconstitution.