Dosage Forms I PDF Fall 2024-2025

10/11/2024 Dosage Forms I M. Mehanna, B.S.Pharm, M.S., Ph.D. School of Pharmacy Lebanese American University Fall 2024-2025 Pharmaceutical Solutions 1  10/11/20...

10/11/2024 Dosage Forms I M. Mehanna, B.S.Pharm, M.S., Ph.D. School of Pharmacy Lebanese American University Fall 2024-2025 Pharmaceutical Solutions 1  10/11/2024 Intended learning outcomes  Describe disperse systems and their general properties  Describe the different types of liquid pharmaceutical preparations and compare their characteristics  Identify the ingredients used in the formulations  Describe the basic manufacturing processes performed during their large-scale preparation Dispersed systems They are consist of particulate matter, known as the dispersed phase, distributed throughout a continuous or dispersion medium. The dispersed material may range in size from particle of atomic and molecular dimensions to particles whose size measured in millimeter. 2  10/11/2024 Dispersed systems Dispersed systems are classified according to their particle size into a. Molecular dispersions b. Colloidal dispersions c. Coarse dispersions 3  10/11/2024 Pharmaceutical solutions Solution is a homogeneous, molecular, mixture of two or more components. The simplest solution consists of two components, a solute dissolved in a solvent such as solid solutes (drug and excipients) are dissolved in a liquid solvent system. Water is the most common solvent, although organic solvents are used in combination with water or on their own. In industry, solutions are prepared in large mixing vessels which are thermostatically controlled should a specific temperature be desired. The solvent system i. Aqueous solvents Water is the most commonly used solvent due to its lack of toxicity and low cost. Naturally occurring water is impure. Purified for drinking usually contains less than 0.1% of total solids. Drinking water must meet the U.S. Public Health Service regulations with respect to bacteriologic purity. It is not acceptable for the manufacture of aqueous pharmaceutical preparations or for the extemporaneous compounding. Different types of ‘water’ have been defined in the pharmacopoeias. 4  10/11/2024 Purified Water, USP Obtained by distillation, ion exchange treatment, or reverse osmosis. It is prepared from water complying with the federal Environmental Protection Agency with respect to drinking water. Purified Water, USP, has fewer solid impurities than ordinary drinking water (0.001%) Purified Water, USP, is intended for use in the preparation of non-parenteral aqueous dosage forms. ii. Non-aqueous solvents Nonaqueous solvent systems are used when the drug is insufficiently soluble or stable in aqueous systems. Although there are a huge number of organic liquids in which drugs can dissolve, the majority are toxic, and consequently only a few are used in pharmaceutical solutions. Examples of commonly used organic liquids are: i. Alcohol ii. Glycerin iii. Propylene glycol 5  10/11/2024 1. Alcohol, USP: Ethyl Alcohol, Ethanol Alcohol is the most useful non-solvent in pharmacy used either as a primary solvent or as a hydroalcoholic mixture. Alcohol, USP, is 94.9-96.0%v/v. Dehydrated Alcohol, USP, also called absolute alcohol, contains not less than 99.5%v/v. Alcohol is preferred because of its miscibility with water and its ability to dissolve many water-insoluble ingredients, and antimicrobial preservatives. U.S. Food and Drug Administration (FDA) has proposed that as possible manufacturers of over-the-counter (OTC) oral drug products restrict the use of alcohol and include appropriate warnings on the label. 2. Glycerin, USP (Glycerol) Clear viscous liquid with a sweet taste. It is miscible with both water and alcohol. Glycerin is often used as a stabilizer and as an auxiliary solvent in conjunction with water or alcohol. 3. Propylene Glycol, USP, 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. 6  10/11/2024 Preparation of solutions 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 (drug deterioration), reducing the particle size of the solute, using a solubilizing agent, and/or subjecting the ingredients to vigorous agitation. 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. When heat is desired, thermostatically controlled mixing tanks may be used. 7  10/11/2024 I. Oral Solutions Oral rehydration solution (ORT) Rapid fluid loss associated with diarrhea can lead to dehydration and ultimately death in some patients, particularly infants, mostly due to hypovolemic shock. The treatment approach is to allow the diarrhea to proceed and not to terminate it too quickly but promptly replace the lost fluid and electrolytes to prevent dehydration. Glucose is actively absorbed from the small intestine. Its active transport is coupled with sodium absorption which in turn promotes anions and water absorption. The optimal concentrations of glucose and sodium in an isotonic solution are 110 mM (2%) glucose and 60 mEq/L of sodium ion, respectively. 8  10/11/2024 Oral Colonic Lavage Solution To prepare the gastrointestinal tract for colonoscopy. Oral administration of a balanced solution of electrolytes with polyethylene glycol. Before dispensing it to the patient, the pharmacist reconstitutes this powder with water, creating an iso-osmotic solution having a mildly salty taste. The PEG acts as an osmotic agent in the GIT, 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. Oral colonic lavage solution: PEG-3350 240.00 g Sodium sulfate 22.72 g Sodium bicarbonate 6.72 g Sodium chloride 5.84 g Potassium chloride 2.98 g in 4,000 mL disposable container Dose: drink 240 mL of solution every 10 minutes until about 4 L is consumed. Storage: product must be stored in the refrigerator after reconstitution, and this aids somewhat in decreasing the salty taste of the product 9  10/11/2024 II. Syrups Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. These syrups are intended to serve as pleasant-tasting vehicle. Any water-soluble drug that is stable in aqueous solution may be added to a flavored syrup but ensure compatibility. Flavored acidic syrups may affect the solubility and the stability of any added drug. Medicated syrups are antitussive agents and antihistamines. Components of Syrups: (a) the sugar, usually sucrose, or sugar substitute used to provide sweetness and viscosity (b) antimicrobial preservative (c) Flavorants (d) Colorants (e) others, including alcohol, solubilizing agents, thickeners, or stabilizers. 10  10/11/2024 1. Sucrose- and non-sucrose-based syrups Sucrose is the sugar most frequently employed. It may be replaced partially or totally by sorbitol, glycerin, and propylene glycol. In some cases, glycogenetic substances, are replaced by non- glycogenetic substances, such as methylcellulose or hydroxyethylcellulose for diabetic patients and others whose diet must be controlled and restricted. Their viscosities are much like that of a sucrose syrup. The addition of one or more artificial sweeteners usually produces an excellent true syrup The viscosity together with the sweetness and flavorants, results in a type of pharmaceutical preparation that masks the taste of added drug. For antitussive syrups, the thick, sweet syrup has a soothing effect on the irritated tissues of the throat. increase osmotic pressure of water Syrup, NF, also called simple syrup. It is prepared by dissolving 85 g of sucrose in enough purified water to make 100 mL of syrup Microbial stability of syrups; dilute sucrose solutions is an efficient nutrient medium for the growth of microorganisms, On the other hand, concentrated sugar solutions are quite resistant to microbial growth due to osmotic effect and water unavailability. 11  10/11/2024 The resulting preparation generally requires no additional preservation, in the official syrup. If the syrup were completely saturated with sucrose, in cool storage, some sucrose might crystallize from solution. Sorbitol Solution, USP, is employed as shown in the following example formulation: 2. Antimicrobial Preservative preservatives commonly used in syrups with the usually effective concentrations are benzoic acid (0.1-0.2%), sodium benzoate (0.1-0.2%), and various combinations of methylparabens, propylparabens, and butylparabens totaling about 0.1%. alcohol is used in syrups to assist in dissolving the alcohol- soluble ingredients, but normally, it is not present in the final product in amounts that would be considered to be adequate for preservation (15% to 20%). 12  10/11/2024 3. Flavorant Most syrups are flavored with synthetic flavorants or with naturally occurring materials, such as volatile oils (e.g., orange oil), and vanillin, to render the syrup pleasant tasting. The flavorant should be water soluble. However, sometimes a small amount of alcohol is added to a syrup to ensure the continued solution of a poorly water-soluble flavorant. 4. Colorant To enhance the appeal of the syrup, a coloring agent that correlates with the flavorant employed (i.e., green with mint, brown with chocolate) is used. Generally, the colorant is water soluble, non-reactive with the other syrup components, and color stable at the pH range and under the intensity of light that the syrup is likely to encounter during its shelf life. 13  10/11/2024 Preparation of Syrups Syrups are most frequently prepared by one of four general methods, depending on the physical and chemical characteristics of the ingredients. 1. Solution of the ingredients with the aid of heat (invert sugar) 2. Solution of the ingredients by agitation 3. Addition of sucrose to a prepared medicated liquid (extract) 4. Percolation of either the source of the medicating substance or the sucrose. III. Elixirs Clear, sweetened hydroalcoholic solutions intended for oral use and are flavored to enhance their palatability. Compared with syrups, elixirs are less sweet and less viscous. As a results of its hydroalcoholic character, elixirs are better to solubilize both water- and alcohol-soluble components. E.g Digoxin Elixir 14  10/11/2024 The proportion of alcohol in elixirs varies widely due to solubility of the drugs. Glycerin and propylene glycol, may be employed as adjunctive solvents. Elixirs having a high alcoholic content usually use an artificial sweetener, such as saccharin, which is required only in small amounts, rather than sucrose. Elixirs containing more than 10% to 12% of alcohol are usually self-preserving. The disadvantage of elixirs for children and for adults who choose to avoid alcohol is their alcoholic content due to its pharmacological and toxicological effects. Due to the presence of volatile content as oils and alcohol, elixirs should be stored in tight, light-resistant containers and protected from excessive heat. 15  10/11/2024 IV. Tinctures Alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical substances. Depending on the preparation, alcohol concentration is 15%- 80% thus it protects against microbial growth and keeps the alcohol-soluble extractives in solution. Tinctures must be tightly stoppered and not exposed to excessive temperatures. Opium Tincture, USP, contains 10% opium (1% morphine) and camphorated tincture of opium contains (0.04% morphine). Topical solutions and tinctures Topical solutions and tinctures should be packaged in containers that make them convenient to use. E.g. Chlorhexidine gluconate solution and Povidone Iodine topical solution mouth wash and betadine 16  10/11/2024 Aluminum subacetate topical solution In the subacetate solution, the ratio of aluminum oxide to acetic acid is 1:2.35, whereas in the acetate solution, the ratio is 1:3.52. subacetate is used to make aluminum Aluminum subacetate topical solution, is used in preparation acetate and we dilute it of aluminum acetate topical solution. with water Aluminum acetate topical solution, diluted first with 20 to 40 parts of water, is used externally as an astringent wash and wet dressing (modified Burow solution). 17  10/11/2024 H2O2 Hydrogen peroxide topical solution The solution contains 2.5- 3.5% (w/v) hydrogen peroxide. it is an oxidizing agent that releases The dilute solution, which contains about 3% hydrogen oxygen we measure the amount of peroxide, liberates 10 times its volume of oxygen (10-volume oxygen released and call it 10-volume peroxide). Hydrogen peroxide solution is used as a local anti-infective for use topically Germicidal activity is based on the release of active oxygen on contact with the tissues also its ability to cleanse wounds by mechanical action through the the release of oxygen. Iodine Tincture Iodine tincture is prepared by dissolving 2% iodine crystals and 2.4% sodium iodide in an amount of alcohol equal to half the volume of tincture to be prepared and diluting the solution to volume with sufficient purified water. Triiodide form of iodine is its water solubility. Local anti-infective agent applied to the skin in general household first aid. The tincture should be stored in a tight container to prevent loss of alcohol. 18  10/11/2024 Dental solutions Benzocaine: topical anesthetic for temporary relief of pain, soreness, and irritation in the mouth associated with teething. Nystatin oral suspension: antifungal Saliva substitutes: electrolytes in a carboxymethylcellulose base. They are indicated for relief of dry mouth and throat. Some of these products are medicated, whereas others are used for hygienic purposes, such as dentifrices, and denture products. Vaginal and Rectal solutions Vaginal douches Solutions may be prepared from powders or from liquid solutions or liquid concentrates. Products are used to prepare solutions for vaginal douche, that is, for irrigation cleansing of the vagina. A few douche products containing specific therapeutic anti- infective agents. 19  10/11/2024 Among the components of douche powders: 1. Boric acid or sodium borate 2. Astringents: alum, ammonium alum, and zinc sulfate 3. Antimicrobials: oxyquinoline sulfate and povidone iodine 4. Quaternary ammonium compounds: benzethonium chloride 5. Detergents: sodium lauryl sulfate 6. Oxidizing agents: sodium perborate 7. Salts: sodium citrate and sodium chloride 8. Aromatics: menthol, thymol, and eucalyptol douche mostly contain sodium borate or boric acid and main function to adjust pH of vagina and may contain oxidizer like sodium perborate Retention enemas A number of solutions are administered rectally for local effects or for systemic absorption. Clinically effective blood levels of the agents are usually obtained within 30 minutes following rectal instillation. 20  10/11/2024 Evacuation enemas Rectal enemas are used to cleanse the bowel. The agents are solutions of sodium phosphate and sodium no need to memorize biphosphate, glycerin and docusate potassium, and light mineral oil. The patient should be advised to gently insert the tip of the product with steady pressure and be told that it is not necessary to squeeze all of the contents out of the disposable plastic bottle. The patient should be told that the product will most probably work within 5 to 10 minutes. Aromatic waters Clear, aqueous solutions saturated with volatile oils or other aromatic or volatile substances. Aromatic waters such as orange flower oil, peppermint oil, rose oil, anise oil, camphor, and chloroform. Most of the aromatic substances in the preparation of aromatic waters have very low solubility in water, and even though the water may be saturated, its concentration of aromatic material is still rather small. Aromatic waters may be used for perfuming and/or flavoring. 21  10/11/2024 Spirits Alcoholic or hydroalcoholic solutions of volatile substances. With high alcoholic concentration usually over 60%. Upon mixing with water, the volatile substances present in spirits separate and form a milky preparation. Used as flavouring agents and medicinally for the therapeutic value of the aromatic solute. For medicinal purposes, spirits may be taken orally, applied externally, or used by inhalation. The spirits most recently official in the USP–NF are aromatic ammonia spirit, camphor spirit, compound orange spirit, and peppermint spirit. Non-aqueous solutions I. Liniments Alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to be rubbed on the skin. Alcoholic ones are useful when counterirritant, or penetrating action is desired. Oleaginous liniments are employed primarily when massage is desired (almond oil, peanut oil). They are less irritating to the skin than alcoholic liniments. All liniments should bear a label indicating that they are suitable only for external use and must never be taken internally. Liniments should be stored in tight containers. 22  10/11/2024 II. Collodions Liquid preparations composed of pyroxylin dissolved in a solvent mixture of alcohol and ether with or without added medicinal substances. Pyroxylin (nitrocellulose), obtained from cotton. One part of pyroxylin is slowly but completely soluble in mixture of ether and alcohol. Collodions are intended for external use. When applied to the skin, the solvent rapidly evaporates, leaving a filmy residue. This provides an occlusive protective coating to the skin. Collodions should be applied to dry tissues to adhere to the skin surface. Flexible collodion Flexible collodion is prepared by adding 2% camphor and 3% castor oil to collodion. The castor oil renders the product flexible, permitting its comfortable use over skin areas that are normally moved, such as joints, fingers, and toes. Salicylic acid collodion 10% salicylic acid in flexible collodion. It is used for its keratolytic effects, especially in the removal of corns from the toes. Because salicylic acid can irritate normal, healthy skin, every attempt must be made to ensure application directly on the corn or wart. A useful preventive measure is to line the adjacent healthy skin with some white petrolatum prior to application of the product. 23 10/11/2024 24