Pharmaceutical Technology - Preparation of Solutions PDF

# Pharmaceutical Technology - Preparation of Solutions Most pharmaceutical solutions are unsaturated with solute. Thus, the amounts of solute to be dissolved are usually well below the capacity of the solvent used. The strengths of these preparations are usually expressed in terms of percent streng...

# Pharmaceutical Technology - Preparation of Solutions Most pharmaceutical solutions are unsaturated with solute. Thus, the amounts of solute to be dissolved are usually well below the capacity of the solvent used. The strengths of these preparations are usually expressed in terms of percent strength, though for very dilute preparations, expressions of ratio strength may be used. The symbol "%" used without qualification (as with "/v", "/w", or "/w") represents: - **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. - **Weight in weight** for mixtures of solids and semisolids. Some chemical agents in a solvent require extended time for dissolving. This may require applying heat, reducing the particle size of the solute, using a solubilizing agent, or subjecting the ingredients to vigorous agitation. Pharmacists generally prefer to avoid using heat to facilitate solution, and when they do, they are careful not to exceed the minimally required temperature to avoid medicinal agents destruction and drug deterioration. If volatile solutes are to be dissolved or if the solvent is volatile, heat should be avoided as it may encourage the loss of these agents to the atmosphere. Pharmacists are aware that certain chemical agents, particularly calcium salts, undergo exothermic reactions as they dissolve and give off heat. 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 can be accomplished by comminution with a mortar and pestle on a small scale or with an industrial micronizer on a larger scale. The reduced particle size increases the surface area of the solute, so if the powder is placed in a suitable vessel with a portion of the solvent, the rate of solution may be increased by continued circulation of fresh solvent to the drug's surface. Most solutions are prepared by simple mixing of the solutes with the solvent. On an industrial scale, solutions are prepared in large mixing vessels with ports for mechanical stirrers. Thermostatically controlled mixing tanks may be used when heat is desired. **Note:** Pharmaceutical preparations are stable if they have no loss in therapeutic activity or undesirable chemical and physical changes over extended periods of time. Drug expiration dates reflect the time period during which the product is known to remain stable, meaning it retains its strength, quality, and purity when stored according to the labeled conditions. Shelf life can be defined as the time required for the drug level in a product stored at room temperature (normally 25°C) to degrade to 90 percent of its labeled potency. # Oral Solutions Most solutions intended for oral administration contain flavorants and colorants to make the medication more attractive and palatable. 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 pharmacist must be wary of chemical interactions between the various components of a solution that may alter the preparation's stability and/or potency. Liquid pharmaceuticals for oral administration are usually formulated such that the patient receives the usual dose of the medication in a small volume, such as 5 mL (one teaspoonful), 10 mL, or 15 mL (one tablespoonful). **Properties of Oral Solutions:** * **Palatable** - means that the preparations must be acceptable by the patient in terms of taste, appearance, and odor to a reasonable degree. This is affected by many factors like the age of the patient, pharmaceutical dosage form, whether or not the taste needs to be improved, and the color of the drug. * **Stability** - the drug should be stable enough to ensure that the patient will receive the stated amount on the label. It should also remain stable for a period of time when stored at room temperature to ensure that the patient will take the precise dose. * **Effective** - the drug should be effective when taken by the patient in terms of absorption, distribution, and other properties. # Dry Mixtures for Solution A number of medicinal agents, particularly certain antibiotics, lack sufficient stability in aqueous solution to meet extended shelf life periods. Thus, commercial manufacturers of these products often provide them to the pharmacist as 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 the drug, flavorant, colorant, buffers, and others, except for the solvent. Once reconstituted, the solution remains stable when stored in the refrigerator for the labeled period, usually 7 to 14 days, depending on the preparation. This is typically a sufficient period for the patient to complete the regimen usually prescribed. However, in case medication remains after the patient completes the course of therapy, the patient should be instructed to discard the remaining portion. # Oral Solutions The pharmacist may: * 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. * Compound an oral solution from bulk components. In each instance, pharmacists should be aware about the dispensed product to advise the patient of the proper use, dosage, method of administration, and storage of the product. Knowledge of the solubility and stability characteristics of the medicinal agents and the solvents employed is useful to the pharmacist for informing the patient of the advisability of mixing the solution with juice, milk, or other liquids. # Oral Rehydration Solutions Rapid fluid loss associated with diarrhea can lead to dehydration and ultimately death in some patients, particularly infants. Diarrhea is characterized by an increased frequency of loose, watery stools, and because of the rapid fluid loss, dehydration can be an outcome. The loss of fluid during diarrhea is accompanied by depletion of sodium, potassium, and bicarbonate ions; if severe, the loss can result in acidosis, hyperpnea, and vomiting as well as hypovolemic shock. If continuous, vomiting and diarrhea can cause malnutrition as well. The goal of rehydration is to replace lost fecal water with an oral rehydration solution and use nutritional foods, such as soybean formula and bran. Oral rehydration salts solutions (ORS) 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. # Oral Colonic Lavage Solution Traditionally, preparation of the bowel for procedures such as a colonoscopy consisted of administration of a clear liquid diet for 24 hours preceding the procedure, administration of an oral laxative such as magnesium citrate or bisacodyl the night before, and a cleansing enema administered 2 to 4 hours prior to the procedure. However, while the results have been satisfactory, that is, the bowel is cleared for the procedure, poor compliance with and acceptance of this regimen can cause problems during the procedure. Also, additive effects of malnutrition and poor oral intake prior to the procedure can cause more patient problems. Consequently, an alternative method has been devised. This procedure requires less time and dietary restriction and obviates cleansing enemas. This method entails oral administration of a balanced solution of electrolytes with polyethylene glycol (PEG-3350). Before dispensing it to the patient, the pharmacist reconstitutes this powder with water, creating an iso-osmotic solution having a mild salty taste. The PEG acts as an osmotic agent in the gastrointestinal tract, and the balanced electrolyte concentration results in virtually no net absorption or secretion of ions. Thus, a large volume of this solution can be administered without a significant change in water or electrolyte balance. The formulation of this oral colonic lavage solution is as follows: | Composition | Amount | |---|---| | PEG-3350 | 236.00 g | | Sodium sulfate | 22.74 g| | Sodium bicarbonate | 6.74 g | | Sodium chloride | 5.86 g | | Potassium chloride | 2.97 g | The recommended adult dose of this product is 4 L of solution before the gastrointestinal procedure. The patient is instructed to drink 240mL of solution every 10 minutes until about 4 L is consumed. The patient is advised to drink each portion quickly rather than sipping it continuously. Usually, the first bowel movement will occur within 1 hour. Several regions are used, and one method is to schedule patients for a midmorning procedure, allowing the patient 3 hours for drinking and a 1 hour waiting period to complete bowel evacuation. # 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. It is required to contain an amount of magnesium citrate equivalent to 1.55 to 1.9 g of magnesium oxide in each 100 mL. 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. (MgCO3)4 Mg(OH)2 + 5H3C6H5O7 → 5MgHC6H5O7 + 4CO2 + 6H2O 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. # Sodium Citrate and Citric Acid Oral Solution This official solution contains sodium citrate 100 mg and citric acid 67 mg in each milliliter of aqueous solution. The solution is administered orally in doses of 10 to 30 mL as frequently as four times daily as a systemic alkalinizer. Systemic alkalinization is useful for patients for whom long-term maintenance of an alkaline urine is desirable, such as those with uric acid and cystine calculi of the urinary tract. It is also a useful adjuvant when administered with uricosuric agents in gout therapy, since urates tend to crystallize out of an acidic urine. # Miscellaneous Solutions ## Aromatic Waters Aromatic waters are clear, aqueous solutions saturated with volatile oils or other aromatic or volatile substances. * Aromatic waters provide a pleasantly flavored medium for the administration of water-soluble drugs and for the liquid phase of emulsion and suspensions. * Aromatic waters are not therapeutically potent because of the very small proportion of active ingredient present in them. * Aromatic waters were prepared from a number of volatile substances, including orange flower oil, peppermint oil, rose oil, anise oil, spearmint oil, wintergreen oil, camphor, and chloroform. ## Diluted Acids Diluted acids are aqueous solutions prepared by diluting the concentrated acids with purified water. The strength of a diluted acid is generally expressed on a percent weight-to-volume (% w/v) basis, whereas the strength of a concentrated acid is generally expressed in terms of percent weight to weight (% w/w). There is very little use of diluted acids in medicine today. However, because of its antibacterial effects, acetic acid finds application as a 1% solution in surgical dressings.