Fundamentals Of Pharmaceutics (PHT 220) PDF

FUNDAMENTALS OF PHARMACEUTICS (PHT 220) Course coordinator: Adel Al Fatease, Ph.D. Office hours: By appointment [email protected] 10/1/2024  Understand Understand the dif...

FUNDAMENTALS OF PHARMACEUTICS (PHT 220) Course coordinator: Adel Al Fatease, Ph.D. Office hours: By appointment [email protected] 10/1/2024  Understand Understand the different dosage forms and route of administration. Explain parts of prescription and labelling requirements of compounding and Explain controlled substances. Course Recall Recall Latin numerals and abbreviations used in prescriptions. Recognize Objectives Recognize intersystem conversions between metric and imperial systems. Understand the various basic pharmaceutical calculations important in Understand compounding prescriptions including % concentration, molarity, dilution and concentration and allegation. Describe the science and the correct procedures for compounding Describe extemporaneous preparation. Define Define ADME, analyze, and overcome pharmaceutical incompatibilities. 10/1/2024 Introduction To Dosage Forms 10/1/2024  Terminology Pharmaceutics (The science of dosage form design): The general area of study which concerns itself with the physical, chemical and biological factors which influence the formulation, manufacture, stability and effectiveness of pharmaceutical dosage form. Dosage form: The final form in which the drug is presented to the patients that is unique in its physical and pharmaceutical characteristics. 10/1/2024  Terminology Dose of a drug: The amount which may be expected ordinarily to produce, in adults, the medicinal effect for which it was officially recognized. Dosage regimen: The schedule of the dosage is frequently given or the manner in which the drug is taken (e.g. three times per day for a week). 10/1/2024  Dosage Forms The final form in which the drug is presented to the patients that is unique in its physical and pharmaceutical characteristics. It provides the manufacturing pharmacist with the challenges of formulation and the physician with the choice of pharmaceutical types. 10/1/2024  Reasons For The Need of Dosage Forms 1. A mechanism for safe and convenient delivers of accurate dosage. 2. Protection of a drug from the destructive influences of atmospheric oxygen or moisture (e.g., coated tablets, sealed ampoules). 3. Protection of a drug substance from the destructive influence of gastric acid after oral administration (e.g., coated tablets). 4. Conceal the bitter, salty or obnoxious taste or odor of a drug substance (capsules, coated tablets, flavored syrup). 10/1/2024 5- Liquid preparations of substances that are either insoluble or unstable in the desired vehicle (suspension). 6- Liquid preparations of substances soluble in the desired vehicle (e.g., solution). 7- Extended drug action through controlled release mechanism (e.g., various controlled release tablets, capsules and suspension). 8- Optimal drug action from topical administration sites (e.g., ointments, cream, ophthalmic, ear and nasal preparations). 9- For the insertion of a drug into one of the body’s orifices (e.g., rectal or vaginal suppositories). 10- For the placement of drugs within body tissues (e.g., injection). 11- For optimal drug action through inhalation therapy (e.g., inhalants 10/1/2024 and inhalation aerosols).  CLASSIFICATION: I- Liquid Dosage Forms: a-Solutions b-Colloids (Dispersion) c-Suspensions d-Emulsions 2-Semisolid Dosage Forms: Ointments, creams, pastes 3-Solid Dosage Forms: Powders, Granules, Tablets, Capsules 10/1/2024  I-Liquid Dosage Form Solution: The solutions are homogenous mixture that is prepared by dissolving a solid, liquid or gas in another liquid and represent a group of preparations in which the molecules of the solute or dissolved substance are dispersed among those of the solvent. A- Aqueous solution: A liquid preparation that contains one or more soluble chemical substances dissolved in water. Solutions are used for the specific therapeutic effect of the solute either internally or externally. 10/1/2024  Antibacterial topical solutions: Kill bacteria when applied to the skin or mucous membrane in the proper strength and under appropriate conditions (e.g., benzalkonium chloride, strong iodine, povidone-iodine solution). Aromatic waters: are clear, saturated aqueous solutions of volatile oils or other aromatic or volatile materials. Aromatic waters may be used as pleasantly flavored vehicles for a water- soluble drug or as an aqueous phase in an emulsion or suspension. Mixtures: are usually aqueous preparations that can be in the form of either a solution or a suspension. Most preparations of this type are manufactured on a small scale as required and are allocated a shelf-life of a few weeks before dispensing. 10/1/2024  Draughts: are mixtures of which only one or two doses of about 50 ml are given although smaller doses are often necessary for children. Oral drops: are oral solutions or suspensions, which are administered, in small volumes, using a suitable measuring device. Douches: are aqueous solution directed against a part or into a cavity of the body (e.g., eye douches, pharyngeal douches, nasal douches and vaginal douches). The most common type of douches is vaginal douches which used for cleansing the vagina. 10/1/2024  Enema: are rectal preparations employed to evacuate the bowel (evacuation enema), influence the general system by absorption or to affect locally the seat of disease (retention enemas). Retention enemas may possess anthelmintic, nutritive, sedative or stimulating properties or they may contain radiopaque substances for examination of the lower bowel. Parenteral products: Sterile solutions for injection or infusion into the body. Gargles: are aqueous solutions frequently containing antiseptics, antibiotics and/or anesthetics used for treating the pharynx and nasopharynx by forcing air from the lungs through the gargle which is held in the throat; subsequently the gargle is expectorated. Many gargles must be diluted with water before use. 10/1/2024  Mouth washes: are solutions used for cleansing the mouth or treating diseased conditions of the oral mucous membrane. They frequently contain alcohol or glycerin to aid in dissolving the volatile ingredients and more often used cosmetically than therapeutically. Nasal solutions: are usually aqueous solutions designed to be administered to the nasal passages in drops or sprays. Many of drugs are administered for their local sympathomimetic effect such as ephedrine sulphate or naphazoline hydrochloride to reduce nasal congestion. Few preparations are administered in spray form for their systemic effect. 10/1/2024  Otic solutions (aural preparations): Aqueous solution for topical application in the ears. The main classes of drugs used for ear include analgesics, antibiotics and anti-inflammatory agents. Irrigation solutions: The solutions are used to wash or bathe surgical incisions, wounds or body tissues. 10/1/2024  Sweet or other viscid aqueous solutions Syrups: are concentrated solutions of sugar such as sucrose in water or another aqueous liquid. Simple syrup: When purified water alone is used in making the solution of sucrose. Flavored syrup: Is one which usually is not medicated but which contains various aromatic or pleasantly flavored substances and intended to be used as a vehicle or flavor for prescription. Medicated syrup: When aqueous preparation contains some added-medicinal substances. 10/1/2024  Linctuses:  are viscous preparations usually prescribed for the relief of cough.  It is normally consists of a simple solution of the active agent in a high concentration of sucrose, often with other sweetening agents. This type of product should be sipped slowly and not be diluted beforehand. The syrup content has a demulcent action on the mucous membranes of the throat. 10/1/2024  B-Non aqueous solutions  Collodions: Are liquid preparations containing pyroxylin (a nitrocellulose) in a mixture of ethyl ether and ethanol. They are applied to the skin by means of a soft brush or other suitable applicator and when ether and ethanol have evaporated, leave a film of pyroxylin on the surface. Example: Salicylic acid collodion (10% salicylic acid), used as a keratolytic agent in the treatment of corns and warts.  Liniments: liquid preparations are intended for massage into the skin and can contain such ingredients as methyl salicylate as counter irritants. 10/1/2024  Paints: liquids for application to the skin or mucous membranes in small amounts with a small brush. The solvent is normally alcohol, acetone or ether which evaporates quickly leaving a film on the skin that contains the active agent. Elixirs: are clear, pleasantly flavored, sweetened hydro alcoholic liquids intended for oral use. The main ingredients in elixirs are ethanol and water but glycerin, sorbitol, propylene glycol, flavoring agents, preservatives and syrups often are used in the preparation of final products. 10/1/2024  Intermediate products Tinctures: Alcoholic or hydro alcoholic solutions of chemicals or soluble constituents of vegetable drugs. Although tinctures vary in drug concentration (up to 50%), those prepared from potent drugs are usually 10% in strength (i.e., 100 ml of the tincture has the activity of 10 gm of the drug). 10/1/2024  Spirits: (also called essences) are alcoholic or hydro alcoholic solutions of volatile substances containing 50%-90% alcohol. This high alcoholic content maintains the water-insoluble volatile oils in solution. Some spirits are medicinal spirits as aromatic ammonia spirit. Another spirits as compound orange spirit and compound cardamom spirit are used as flavoring agent. Fluidextracts: are liquid extracts of vegetable drugs containing alcohol as a solvent, preservative or both. Fluidextracts are prepared by percolation so that each milliliter contains the therapeutic constituents of 1 gm of the standard drug. Fluidextracts of potent drugs are usually 10 times as concentrated as the corresponding tincture. 10/1/2024  Dispersions When two different substances are mixed together so that they mingle intimately, a two-component system is produced. When one component is distributed uniformly throughout the second, the first component is called the dispersed phase and the second, the dispersion medium or continuous phase. Either phase may be solid, liquid, or gas. a-Molecular dispersions (e.g. Glucose in water) b-Colloidal dispersions (e.g. butter, milk) c-Fine dispersions ▪ Size 0.5 μm – 10 μm. ▪ Examples are magmas, gels, powder aerosols d-Coarse dispersions ▪ Size 10 μm – 50 μm or greater ▪ Examples are suspensions, emulsions, foams, some aerosols 10/1/2024  Emulsion: An emulsion is a thermodynamically unstable two-phase system consisting of at least two immiscible liquids, one of which is dispersed in the finely subdivided and uniformly distributed as droplets (diameters ranging from about 0.2-50 μm) throughout the other. The system is stabilized by the presence of a third substance termed emulsifying agent (emulgent). Suspension: are preparations of finely divided drugs held in suspension throughout a suitable vehicle. Suspension taken orally generally is employing an aqueous vehicle, whereas those employed for other purposes may utilize a different vehicle. 10/1/2024 Advantages of liquid dosage forms: 1. The drug might be more effective in liquid dosage forms (e.g., adsorbents, antacids). 2. They can be useful for patients who have trouble swallowing solid dosage forms (e.g., pediatric and geriatric dosage forms). Disadvantages of liquid dosage forms: 1. Bulkier dosage forms. 2. Degrade more readily. 3. More likely to interact with constituents than those in solid forms. 10/1/2024  II-Semisolid Dosage Forms: Ointments: are semisolid preparations in which the drug is contained in a suitable base which is itself semisolid and either hydrophilic or hydrophobic in character. Those intended for application to the eye are specially prepared and termed “ophthalmic ointments”. Creams: are semisolid emulsions and are generally less viscid and lighter than ointments. Creams are considered to have greater esthetic appeal due to their non-greasy character and their ability to “vanish” into the skin upon rubbing. C:\Users\DELL\Desktop\New Folder\ALLLLLLLLL\Mohamed\Ointments_files\ointtubt.jpg 10/1/2024  Gels: are semisolid systems consisting of dispersion made up of either small inorganic molecules or large organic molecules enclosining and interpenetrated by a liquid. Pastes: Like ointments, are intended for external application to the skin. They differ than ointments primarily in that they generally contain more solid materials than do ointments and are therefore stiffer and less penetrating. Pastes are usually applied for their ability to absorb serous discharges from skin lesions. Thus when protective rather than therapeutic action. 10/1/2024  III-Solid Dosage Form Powders: are mixtures of finely divided drugs and/or chemicals in dry form. This should be differentiated from the general use of the term “powder” or “powdered” which is commonly used to describe the physical state of a single chemical substance or a drug. Granules: are prepared agglomerates of smaller particles. They are generally irregular in shape and behave as single larger particles. Effervescent salts: are granules or coarse to very coarse powders containing a medicinal agent in a dry mixture usually composed of sodium bicarbonate, citric acid and tartaric acid. When added to water, the acids and base react to liberate carbon dioxide resulting in effervescence. 10/1/2024  Tablets: are solid dosage forms prepared by compression or molding and contain medicinal substances with or without suitable diluents, disintegrants, coating, colorants and other pharmaceutical adjuncts. Image:Eff tablets.jpg Capsules: are solid dosage forms in which the drug substances and such appropriate pharmaceutical adjuncts as fillers are enclosed in either a hard or a soft “shell” which is generally composed of a form of gelatin 10/1/2024  Pills: are small, round solid dosage forms containing a medicinal agent and intended to be administered orally. Pellets: are sterile, small, usually cylindrical shaped solid objects, prepared by compression and intended to implant subcutaneously for the purpose of providing the continuous release of medication over prolonged period of time. 10/1/2024  Lozenges (Troches): are disc shaped solid dosage forms containing a medicinal substance and generally flavoring and sweetening agents intended to be dissolved slowly in the oral cavity for local effect. Suppositories: are solid dosages forms intended for insertion into body orifices where they melt, soften or dissolve and exert localized or systemic effects. 10/1/2024  IV-Miscellaneous Lotions: are generally suspensions of solid materials in an aqueous vehicle although certain emulsions and some true solutions have been designated as lotion because of their appearance or applications. Lotions may be preferred over semisolid preparations because of their non-greasy character and their increased spreadability over large areas of skin. Aerosols: are pressurized dosage forms containing one or more active ingredients which upon actuation give a fine dispersion of liquid and/or solid materials in a gaseous medium. Sprays: are aqueous solutions in the form of coarse droplets or as finely divided solids to be applied topically, most usually to the nasal pharyngeal tract or to the skin. 10/1/2024  Inhalations: are intended to be fine enough to reach the respiratory tree. The particles must generally be a few microns or less in size. Magmas or (Milk): Are two-phase system in which the gel mass consist of floccules of small distinct particles. Gel and magma are considered colloidal dispersions since they each contain particles of colloidal dimension. 10/1/2024  Plasters: are solid or semisolid adhesive masses spread upon a suitable application to a part of the body to provide prolonged contact at that site. They are used to provide: – Protection. – Mechanical support (non-medicated plasters). – Localized or systemic effects (medicated plasters). 10/1/2024  Routs of Drug Administration Inhalation Oral Buccal/Sublingual Transdermal/Subcutaneous Intravenous Rectal Intramuscular 10/1/2024  Routes of drug administration 1-Parenteral administration: A-Intravenous bolus injection: The drug is injected directly into the blood stream, distributes throughout the body and acts rapidly. B-Intravenous infusion: The drug is given intravenously at a constant input rate. Constant rate intravenous infusion maintains a relatively constant plasma drug concentration. 10/1/2024 C-Intramuscular injection: The drug is injected deep into a skeletal muscle. The rate of absorption depends on the vascularity of the muscle site, the lipid solubility of the drug and the formulation matrix. D-Subcutaneous injection: The drug is injected beneath the skin. Because the subcutaneous region is less vascular than muscle tissue, drug absorption is less rapid. 10/1/2024 E-Intradermal (intracutaneous) injection: The drug is injected into the dermis (i.e., the vascular region of the skin below the epidermis). F-Intrathecal injection: The drug is injected into the spinal fluid. 10/1/2024 G-Intra-articular injection: The drug is injected into the joint. 10/1/2024 F-Intra-arterial injection: The drug is injected into a specific artery to achieve a high drug concentration in a specific tissue before drug distribution occurs throughout the body. Intra-arterial injection is used for diagnostic agents and used occasionally for chemotherapy. 10/1/2024  2-Enteral administration A-Buccal and sublingual administration: A tablet or lozenge is placed under the tongue (sublingual) or in contact with the mucosa (buccal) surface of cheek. This type of administration allows a non-polar, lipid soluble drug to be absorbed across the epithelial lining of the mouth. After buccal or sublingual administration, the drug is absorbed directly into the systemic circulation, bypassing the liver and any first-pass effect. 10/1/2024  Peroral (Oral) drug administration: The drug is administered orally, is swallowed, and undergoes absorption from the gastrointestinal tract through the mesenteric circulation to the hepatic portal vein into the liver and then to the systemic circulation. The peroral route is the most convenient and the safest route. 10/1/2024  Disadvantages of the peroral route:  The drug may not be absorbed from the gastrointestinal tract consistently or completely.  The drug may be digested by gastrointestinal enzymes or decomposed by the acid pH of the stomach.  The drug may irritate the mucosal epithelial cells or complex with the contents of the gastrointestinal tract.  Some drugs may be incompletely absorbed because of first-pass effects or presystemic absorption (e.g., the drug is metabolized by the liver before systemic absorption occurs).  The absorption rate may be erratic because of delayed gastric emptying or changes in intestinal motility. 10/1/2024  3-Rectal administration: The drug in solution (enema) or suppository form is placed in the rectum. Drug diffusion from the solution or release from the suppository leads to absorption across the mucosal surface of the rectum. Drug absorbed in the lower two-thirds of the rectum enters the systemic circulation directly, bypassing the liver and any first-pass effects. 10/1/2024  4-Respiratory tract administration: A-Intranasal administration: The drug contained in solution or suspension is administered to the nasal mucosa, either as a spray or drops. The medication may be used for local (e.g., intranasal decongestant, intranasal spray) or systemic effect. B-Pulmonary inhalation: The drug as liquid or solid particle is inhaled perorally (with a nebulizer or a metered-dose aerosol) into the pulmonary tree. 10/1/2024  5-Transdermal and topical administration: A-Transdermal (percutaneous) drug absorption is the placement of the drug (in a lotion, ointment, cream, paste or patch) on the skin surface for systemic absorption. B-Drugs e.g., antibacterials, local anesthetic agents, are applied topically to the skin for a local effect. 10/1/2024 6-Miscellaneous routes for drug administration: - Include ophthalmic, otic, urethral and vaginal administration. - These routes of administration are generally used for local therapeutic activity. However, some systemic drug absorption may occur. 10/1/2024  Time of onset of action for different dosage forms Dosage form Time of onset of action Seconds I.V. injections I.M and S.C injections, buccal tablets, Minutes aerosols, gases Short term depot injections, solutions, suspensions, powders, granules, Minutes to hours capsules, tablets, sustained release tablets Several hours Enteric coated formulations Days Depot injections, implants Varies Topical preparations 10/1/2024  ADVANTAGES AND DISADVANTAGES FOR PRINCIPAL ROUTES OF DRUG ADMINISTRATION Route Advantages Disadvantages convenient, non-sterile route; inactivation of some drugs by Enternal good absorption for most acid/enzymes; variable Oral drugs absorption; first pass metabolism; G.I. irritation by-passes portal system and infrequent route, few Sublingual avoids first pass; avoids sublingual preparations gastric acid available Rectal as for sublingual; used for infrequent route; variable noctural administration of absorption; aesthetically some drugs unacceptable (in UK) 10/1/2024 Route Advantages Disadvantages Parenteral rapid onset (emergency) route, sterile preparation Intravenous (i/v) continuous infusion; complete required; risk of sepsis or availability; route for drugs that embolism; high drug levels cause local tissue damage at the heart Intramuscular rapid onset of lipid soluble drugs, painful; tissue damage with (i/m) and depot injection for slow prolonged some drugs; absorption subcutaneous release possible variable (s/c) Inhalational lungs ideally suited due to huge few disadvantages surface area; good for volatile agents (anaesthetic gases), aerosols etc. Ideal for local effect Topical ideal for local effect few disadvantages 10/1/2024  Table (1): Dosage forms available for different routs of drug administration. Administration route Dosage form Solutions, syrups, elixirs, suspensions, emulsions, Oral gels, powders granules, capsules, tablets. Suppositories, ointments, creams, powders, solutions. Rectal Ointments, creams, pastes, lotions, gels, solutions, topical Topical aerosols, transderm therapeutic systems (TTS). Injections (solutions, suspensions, or emulsions forms), Parenteral implants, irrigation and dialysis solutions. Aerosols (solution, suspension, emulsion, or powder Lungs forms), inhalations, sprays gases. Nasal Solutions, suspensions inhalations. Eye Solutions, suspensions, ointments. Ear Solutions, suspensions, ointments. 10/1/2024  FACTORS AFFECTING DRUG DOSAGE The dose of a drug has been described as an amount which is "enough but not too much," to produce the drug's optimum therapeutic effect in a particular patient with the lowest possible dose. I. Age. II. Body Weight. III. Body Surface Area. IV. Gender. V. Pathologic State. VI. Tolerance. VII. Concomitant Drug Therapy. VIII. Time of Administration. IX. Route of Administration. -The ability to endure the influence of a drug, particularly when acquired by a continued use of the substance, is referred to tolerance. 10/1/2024