Pharmaceutical Technology 3rd Stage - Lecture 3 & 4 PDF

Lecture 3 &4 Pharmaceutical Technology 3 rd Stage Solvent used in pharmaceutical preparation 1. Water: Good solvent for many inorganic salts and many organic compound.Its miscibility with other solvents such as alcohol and glycerin make it useful vehicle for m...

Lecture 3 &4 Pharmaceutical Technology 3 rd Stage Solvent used in pharmaceutical preparation 1. Water: Good solvent for many inorganic salts and many organic compound.Its miscibility with other solvents such as alcohol and glycerin make it useful vehicle for many pharmaceutical preparation. 2. Alcohol: Ethyl alcohol, ethanol, (94.9-96 % by volume C2H5OH).It is good solvent for many organic substances both natural and synthetic.It dissolves important plant constituents such as resins, volatile oil, alkaloids, and glycosides and it is also used in liquid product as antimicrobial preservatives alone or as a co-preservative with other preservatives like parabens. Alcohol produce solution has greater stability than their aqueous counter parts. Hydroalcoholic liquids are commonly used as solvents for plant constituents because they effectively dissolve the active principles by their negative solvent action. They don’t dissolve therapeutically inert plant material like gums and starches. Alcohol is frequently used with other solvents, as glycols and glycerin to reduce the amount of alcohol required. Since it has undesired pharmacologic and potential toxic effects when ingested in pharmaceutical products particularly by children, so the recommended alcohol content limit is as follows:  For OTC oral products intended for children under 6 years of age, the recommended alcohol limit is 0.5%  For product intended for children 6 to 12 years of age the recommended limit is 5%   For products recommended for children over 12 year and for adults, the recommended limit is 10%. 3. Diluted Alcohol, NF 49-50%: is prepared by mixing equal volume of alcohol, USP, AND Purified Watet, USP and used in manufacture of certain preparation. Such hydroalcoholic liquid or solvent is useful in various pharmaceutical processes and preparations since it dissolves both alcohol- soluble and water-soluble substances. 4. Dehydrated alcohol: 99.5% by volume C2H5OH (absolute alcohol).It is practically free from water so it has greater range of solvent power. 5. Isopropyl alcohol: Used in cosmetic and dermatologic formulation. 6. Glycerin: Glycerin is a clear syrupy liquid with a sweet taste. It is miscible with both 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 and is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. It is used in many internal preparations. It is excellent solvent for tannins, phenol and boric acid. 7. Propylen glycol: Propylene glycol, a viscous liquid, is miscible with water and alcohol. It is a useful solvent with a wide range of applications and is frequently substituted for glycerin in modern pharmaceutical formulations. 8. Polyethylen Glycol 400: It is miscible with water, aceton and alcohol.It dissolve many water soluble organic compounds and contain water insoluble substance e.g. Acetyl salicylic acid, theophylline. 9. Chloroform: It is miscible with alcohol, ether; benzene, solvent hexane, fixed and volatile oil.It dissolve in 210 volume of water. It is not flammable but its vapor is harmful and toxic. Official Solutions: Are liquid preparations that contain one or more soluble chemical substances dissolved in liquid solvent. The solvent used for preparing official solution is water; other liquids such as alcohol & glycerin are specified in some of monograph. Uses: 1. For specific therapeutic effect internally or externally. 2. Used as ingredient in compounding of Rx or in the formation of other official preparation. 3. Reagent in various processes. 4. Solvents for certain substances. 5. Coloring agents for pharmaceutical products. Preparation of Solution: Most pharmaceutical solutions are unsaturated with solute. Thus, the amounts of solute to be dissolved are usually well below the capacity of the volume of solvent employed. The strengths of pharmaceutical preparations are usually expressed in terms of percent strength, although for very dilute preparations, expressions of ratio strength may be used. These expressions and examples are shown in the following table:  The symbol % used without qualification (as with w/v, v/v, or w/w) means percent weight in volume for solutions or suspensions of solids in liquids, percent weight in volume for solutions of gases in liquids, percent volume in volume for solutions of liquids in liquids, and weight in weight for mixtures of solids and semisolids. Some chemical agents in a given solvent require an extended time to dissolve. To hasten dissolution, a pharmacist may employ one of several techniques, such as applying heat, reducing the particle size of the solute, using a solubilizing agent, and/or subjecting the ingredients to vigorous agitation. Most chemical agents are more soluble at elevated temperatures than at room temperature or below because an endothermic reaction between the solute and the solvent uses the energy of the heat to enhance dissolution. Pharmacists are reluctant to use heat to facilitate solution, and when they do, they are careful not to exceed the minimally required temperature, for many medicinal agents are destroyed at elevated temperatures and the advantage of rapid solution may be completely offset by drug deterioration. If volatile solutes are to be dissolved or if the solvent is volatile (as is alcohol), the heat would encourage the loss of these agents to the atmosphere and must therefore be avoided. Pharmacists are aware that certain chemical agents, particularly calcium salts, undergo exothermic reactions as they dissolve and give off heat. For such materials, the use of heat would actually discourage the formation of a solution. The best pharmaceutical example of this type of chemical is calcium hydroxide, which is used in the preparation of Calcium Hydroxide Topical Solution, USP. In addition to or instead of raising the temperature of the solvent to increase the rate of solution, a pharmacist may choose to decrease the particle size of the solute. This may be accomplished by comminution (grinding a solid to a fine state of subdivision) with a mortar and pestle on a small scale or industrial micronizer on a larger scale. Methods for preparation of solution: 1. Solution prepared by simple solution. 2. Solution prepared by chemical reaction. 3. Solution prepared by simple solution with sterilization. 4. Solution prepared by extraction. The first method is the easiest method and simplest method of preparation. Sometimes if a solution could be prepared by simple solution and by chemical reaction, then solution prepared by simple solution is preferred. This is because chemical reaction is not easy method; it involves using many reagents resulting in many compounds hard to be purified. It contains all the products of the reaction that have taken place during the method of preparation. However, there is still some substances can be form solution by both simple solution and chemical reaction. For example Ca(OH)2 solution which known as lime water is prepared according to simple solution by dissolving Ca(OH)2 in water and by chemical reaction by shaking lime CaO with un excess of water as shown in Equation 1 CaO + H O → Ca(OH) ------------- (1) Although simple solution is preferred, sometimes chemical reaction has to be chosen for the following reasons: 1. The pure solute may not dissolve from a solid state in other way than chemical reaction. E.g. Aluminum subacetate which is used as astringent used in wet dressing of eczema. 2. The active constituent is not obtained or not readily usable in a form other than that of solution e.g. formaldehyde solution (active constituent is gas). Formaldehyde solution (formalin) used as disinfectant. Hydrogen peroxide solution (H2O2): is topical anti-infective using to clean wounds, also used as softening ear wax in certain dilution. H2O2 solution liberates 10 times its volume oxygen hence; it is called 10 volume peroxide. 3. Some by products are desired like Mg citrate, which is used as cathartic. Examples of solution prepared by simple solution:  Amaranth solution USP 1%: prepared by dissolving amaranth in purified water. It is used as coloring agent to impart color to clear liquid preparation.  Gentian violet solution USP 1%: gentian violet in hydroalcoholic solution (10% alcohol v/v). It is used as topical local anti-infective it is used topically in undiluted form in infections caused by gram-positive bacteria or by certain parasitic fungi.  Iodine solution NF: it is used as local anti-infective for skin and surgical disinfectant.  Tolnaftate solution USP 1% in a non aqueous homogeneous vehicle of polyethylene glycol 400.  Clindamycin phosphate topical solution: used in treatment of acne vulgaris. Solutions prepared by extraction: for example epinephrine solution (adrenalin chloride USP) diluted to 1:1000 in purified water. It is prepared with the help of hydrochloric acid; it is used as vasoconstrictor to increase blood pressure, to prevent hemorrhage and to prolong action of local anesthetic for dentistry purposes. Solution prepared by simple solution with sterilization  Anti-coagulants: 1. Heparin solution USP sterile solution of 75,000 units of sodium heparin in sodium chloride injection. 2. Citrate, phosphate, dextrose solution: it is sterile solution consist from 3% citric acid, 26.3% sodium citrate, 2.22% sodium biphosphate and 25.5% dextrose.  Irrigating solution: it is used to flush or bathe wounds or surgical tissues, should be sterilized because is used for sensitive areas of the body. Example of irrigating solution aminoacetic acid sterile solution (NF): it consists from sterile solution of 1.5 and 15%.15% aminoacetic acid in water for injection is used for irrigating solution in operation such that of prostate (prostatectomy).  Physiologic solutions: Ringer's solution (NF), it is Isotonic solution consists from 6.6% NaCl , 0.3% KCl, 0.33% CaCl2 diluted in purified water. It cannot be used as parenteral solution, because its solvent is purified water (not water for injection). Ringer's could be considered as irrigating and physiologic solutions, and used as solvent for compound used topically for delicate membrane, use to keep living tissues to reverse all reflexes for a period of time. Ringer's solution, sometimes called trichloride solution (Isotonic solution of trichloride). According to the pharmaceutical used solution may be classified into: 1. Oral solution. 2. Ophthalmic solution.  3. Otic and nasal solution. 4. Topical solution. 5. Parenteral solution. According to their composition solution may be classified into: 1. Syrups (Aqueous solution containing sugar). 2. Elixer (sweetened hydroalcoholic solution). 3. Spirits (solution of aromatic material with alcohol solvent). 4. Aromatic water (solution of aromatic material in water as solvent). 5. Tinctures or fluid extract (prepared by extracting active constituent from crude drug). Oral Solution Most solutions intended for oral administration contain flavorants and colorants to make the medication more attractive and palatable. When needed, they may also contain stabilizers to maintain the chemical and physical stability of the medicinal agents and preservatives to prevent the growth of microorganisms in the solution. The formulation pharmacist must be wary of chemical interactions between the various components of a solution that may alter the preparation’s stability and/or potency. For instance, esters of p-hydroxybenzoic acid (methyl-, ethyl-, propyl-, and butylparabens), frequently used preservatives in oral preparations, have a tendency to partition into certain flavoring oils. This partitioning effect could reduce the effective concentration of the preservatives in the aqueous medium of a pharmaceutical product below the level needed for preservative action Dry Mixtures for Solution: A number of medicinal agents, particularly certain antibiotics, for example, penicillin V, have insufficient stability in aqueous solution to meet extended shelf- life periods. Thus, commercial manufacturers of these products provide them to the pharmacist in dry powder or granule form for reconstitution with a prescribed amount of purified water immediately before dispensing to the patient. The dry powder mixture contains all of the formulative components, including drug, flavorant, colorant, buffers, and others, except for the solvent. Once reconstituted by the pharmacist, the solution remains stable when stored in the refrigerator for the labeled period, usually 7 to 14 days, depending on the preparation. This is a sufficient period for the patient to complete the regimen usually prescribed. However, in case the medication remains after the patient completes the course of therapy, the patient should be instructed to discard the remaining portion, which would be unfit for use at a later time. Oral Solutions The pharmacist may be called on to dispense a commercially prepared oral solution; dilute the concentration of a solution, as in the preparation of a pediatric form of an adult product; prepare a solution by reconstituting a dry powder mixture; or extemporaneously compound an oral solution from bulk ingredients. Knowledge of the solubility and stability characteristics of the medicinal agents and the solvents employed in the commercial products is useful to the pharmacist for informing the patient of the advisability of mixing the solution with juice, milk, or other beverage upon administration. Oral Rehydration Solutions Rapid fluid loss associated with diarrhea can lead to dehydration and ultimately death in some patients, particularly infants. During diarrhea, the small intestine secretes far more than the normal amount of fluid and electrolytes, and this simply exceeds the ability of the large intestine to reabsorb it. This fluid loss, which occurs mostly from the body’s extracellular fluid compartment, can lead to a progressive loss of blood volume culminating in hypovolemic shock. Oral rehydration solutions are usually effective in treatment of patients with mild volume depletion, 5% to 10% of body weight. These are available OTC and are relatively inexpensive, and their use has diminished the incidence of complications associated with parenterally administered electrolyte solutions. A liter of typical oral rehydration solution contains 45 mEq Na+, 20 mEq K+, 35 mEq Cl−, 30 mEq citrate, and 25 g dextrose. These formulations are available in liquid or powder packet form for reconstitution. It is important that the user add the specific amount of water needed to prepare the powder forms. Furthermore, these products should not be mixed with or given with other electrolyte containing liquids, such as milk or fruit juices. Magnesium Citrate Oral Solution Magnesium citrate oral solution is a colorless to slightly yellow clear effervescent liquid having a sweet, acidulous taste and a lemon flavor. It is commonly referred to as citrate or as citrate of magnesia. The solution is prepared by reacting official magnesium carbonate with an excess of citric acid, flavoring and sweetening the solution with lemon oil and syrup, filtering with talc, and then carbonating it by the addition of either potassium or sodium bicarbonate. The solution provides an excellent medium for the growth of molds, and any mold spores present during the manufacture of the solution must be killed if the preparation is to remain stable. For this reason, during the preparation of the solution, the liquid is heated to boiling (prior to carbonation); boiled water is employed to bring the solution to its proper volume; and boiling water is used to rinse the final container. The final solution may be sterilized. The solution is employed as a saline cathartic, with the citric acid, lemon oil, syrup, carbonation, and the low temperature of the refrigerated solution all contributing to the patient’s acceptance of the large volume of medication. For many patients, it is a pleasant way of taking an otherwise bitter saline cathartic. Ophthalmic Solutions: Requirements for Ophthalmic Solutions: 1. The sterility is one of the important consideration in their preparation.Autoclaving in the final container is the preferred method of sterilizing ophthalmic solutions. 2. Preservatives suggested for use in ophthalmic solutions include: a) Phenyl ethyl alcohol 0.5% b) Chlorobutanol 0.5% c) Benzalkonium chloride 0.01%. d) Phenyl mercuric nitrate 0.001% Ophthalmic solutions that are intended for surgical use must be sterile and must not contain any preservative.Such solution should be packaged in single –use disposable container. 3. Ophthalmic solution should be isotonic with lacrial fluid , although the eye can tolerate tonicity values above and below that corresponding to 0.9% NaCl solution is less likely to produce discomfort or irritation to the eye. The agents which is used to adjust the tonicity of solutions must be compatible with the active medicament.  4. pH: The lacrial fluid has pH 7.4 ideally, an ophthalmic solutions should have the same pH as the lacrial fluid ,this is not usually possible because at this pH many drugs are not soluble in water and most alkaloidal salts are precipitate at this level therefore a pH must be found which represents a compromise between optimum stability and maximum therapeutic effect, and this level must be held by buffers. The buffer system that used should have the pH that is nearest to the physiologic pH of 7.4 and at which precipitation of drug does not occure. The USP and NF give formulas for buffer vehicles which may be used for specific drugs. 5. Viscosity: Increase the viscosity of ophthalmic solution offers prolonged contact with the tissue thus enhancing the penetration and therapeutic effect of drug. Thickening agents such as methyl cellulose may be added to increase the viscosity. Proper packaging:  Glass containers.  Plastic containers.  Fixed and screw dropper Contact lenses solutions: 1. Hard. 2. Soft. 3. Rigid gas permeable. Contact lenses solutions:  Wetting solutions.  Cleaning solutions.  Soaking solutions.  Combined purpose solutions.