Ansels Pharmaceutical Dosage Forms And Drug Delivery System Nineth Edition
As has been the hallmark of this
textbook since its first edition more than 40 years ago, each chapter is
written at a level consistent with the requirements of students being
introduced to this area of study. Because this textbook often is used early in
the professional curriculum, it contains important introductory topics, such
as the historical development of drugs and pharmacy, the role of the pharmacist
in contemporize practice, standards of the United States Pharmacopeia-National
Formulary, systems and techniques of pharmaceutical measurement, pharmaceutical
and biopharmaceutical principles applicable to drug product development,
current good manufacturing practice and current good compounding practice
standards, and the regulatory process by which pharmaceuticals are approved for
marketing by the federal Food and Drug Administration.
The detailed presentation of each
dosage form includes physical, physicochemical, and clinical discussions. The
new activities at the end of each chapter are designed to provide opportunities
for creative thought and application of the content.
INTRODUCTION TO DRUGS, DRUG DOSAGE FORMS, AND DRUG DELIVERY SYSTEMS
A drug is defi ned as an agent intended for use in the diagnosis, mitigation, treatment, cure, or prevention of disease in humans or in other animals (Food, Drug, and Cosmetic Act, 1938). One of the most astounding qualities of drugs is the diversity of their actions and effects on the body. This quality enables their selective use in the treatment of a range of common and rare conditions involving virtually every body organ, tissue, and cell.
Some drugs selectively stimulate the cardiac muscle, the central nervous system, or the gas-trointestinal tract, whereas other drugs have the opposite effect. Mydriatic drugs dilate the pupil of the eye, and miotics constrict or diminish pupillary size. Drugs can render blood more coagulable or less coagulable; they can increase the hemoglobin content of the erythrocytes, reduce serum cholesterol, or expand blood volume.
Drugs termed emetics induce vomiting, whereas antiemetic drugs prevent vomiting. Diuretic drugs increase the fl ow of urine; expectorant drugs increase respiratory tract fl uid; and cathartics or laxatives evacuate the bowel. Other drugs decrease the fl ow of urine, diminish body secretions, or induce constipation.
Drugs may be used to reduce pain, fever, thyroid activity, rhinitis, insomnia, gastric acid-ity, motion sickness, blood pressure, and men-tal depression. Other drugs can elevate mood, blood pressure, or activity of the endocrine glands. Drugs can combat infectious disease, destroy intestinal worms, or act as antidotes against the poisoning effects of other drugs. Drugs can assist in smoking cessation or alco-hol withdrawal or can modify obsessive– compulsive disorders.
Drugs are used to treat common infections, AIDS, benign prostatic hyperplasia, cancer, car-diovascular disease, asthma, glaucoma, Alzheimer disease, and male impotence. They can protect against the rejection of transplanted tissues and organs and reduce the incidence of measles and mumps. Antineoplastic drugs provide one means of attacking the cancerous process; radioactive pharmaceuticals provide another. Drugs may be used to diagnose diabetes, liver malfunction, tuberculosis, or pregnancy. They can replenish a body defi cient in antibodies, vitamins, hormones, electrolytes, protein, enzymes, or blood. Drugs can prevent pregnancy, assist fertility, and sus-tain life itself.
Certainly, the vast array of effective medicinal agents available today is one of our greatest scientifi c accomplishments. It is diffi cult to con-ceive our civilization devoid of these remarkable and benefi cial agents. Through their use, many of the diseases that have plagued humans through-out history, such as smallpox and poliomyelitis, are now virtually extinct. Illnesses such as diabe-tes, hypertension, and mental depression are effectively controlled with modern drugs. Today’s surgical procedures would be virtually impossible without the benefi t of anesthetics, analgesics, antibiotics, blood transfusions, and intravenous fl uids.
New drugs may be derived from plant or animal sources, as by-products of microbial growth, or through chemical synthesis, molecu-lar modifi cation, or biotechnology. Computer libraries and data banks of chemical compounds and sophisticated methods of screening for potential biologic activity assist drug discovery.
The process of drug discovery and develop-ment is complex. It entails the collective contri-butions of many scientifi c specialists, including organic, physical, and analytical chemists; bio-chemists; molecular biologists; bacteriologists; physiologists; pharmacologists; toxicologists; hematologists; immunologists; endocrinologists; pathologists; biostatisticians; pharmaceutical scientists; clinical pharmacists; physicians; and many others.
After a potential new drug substance is dis-covered and undergoes defi nitive chemical and physical characterization, a great deal of biologic information must be gathered. The basic phar-macology, or the nature and mechanism of action of the drug on the biologic system, must be determined including toxicologic features. The drug’s site and rate of absorption, its pattern of distribution and concentration within the body, its duration of action, and the method and rate of its elimination or excretion must be stud-ied. Information on the drug’s metabolic degra-dation and the activity of any of its metabolites must be obtained. A comprehensive study of the short-term and long-term effects of the drug on various body cells, tissues, and organs must be made. Highly specifi c information, such as the effect of the drug on the fetus of a pregnant animal or its ability to pass to a nursing baby through the breast milk of its mother, may be obtained. Many a promising new drug has been abandoned because of its potential to cause excessive or hazardous adverse effects.
The most effective routes of administration (e.g., oral, rectal, parenteral, topical) must be determined, and guidelines for the dosages rec-ommended for persons of varying ages (e.g., neo-nates, children, adults, geriatrics), weights, and states of illness have to be established. It has been said that the only difference between a drug and a poison is the dose. To facilitate administration of the drug by the selected routes, appropriate dosage forms, such as tablets, cap-sules, injections, suppositories, ointments, aero-sols, and others, are formulated and prepared. Each of these dosage units is designed to contain a specifi ed quantity of medication for ease and accuracy of dosage administration. These dosage forms are highly sophisticated delivery systems. Their design, development, production, and use are the product of application of the pharma-ceutical sciences—the blending of the basic, applied, and clinical sciences with pharmaceuti-cal technology.
Each particular pharmaceutical product is a formulation unique unto itself. In addition to the active therapeutic ingredients, a pharmaceutical formulation contains a number of nontherapeu-tic or pharmaceutical ingredients. It is through their use that a formulation achieves its unique composition and characteristic physical appear-ance. Pharmaceutical ingredients include such materials as fi llers, thickeners, solvents, suspen-ding agents, tablet coatings and disintegrants, penetration enhancers, stabilizing agents, anti-microbial preservatives, fl avors, colorants, and sweeteners.
To ensure the stability of a drug in a formula-tion and the continued effectiveness of the drug product throughout its usual shelf life, the prin-ciples of chemistry, physical pharmacy, microbi-ology, and pharmaceutical technology must be applied. The formulation must be such that all components are physically and chemically compatible, including the active therapeutic agents, the pharmaceutical ingredients, and the packaging materials. The formulation must be preserved against decomposition due to chemi-cal degradation and protected from microbial contamination and the destructive infl uences of excessive heat, light, and moisture. The thera-peutic ingredients must be released from the dosage form in the proper quantity and in such a manner that the onset and duration of the drug’s action are that which are desired. The pharma-ceutical product must lend itself to effi cient administration and must possess attractive features of fl avor, odor, color, and texture that enhance acceptance by the patient. Finally, the product must be effectively packaged and clearly and completely labeled according to legal regulations.
Once prepared, the pharmaceutical product must be properly administered if the patient is to receive maximum benefi t. The medication must be taken in suffi cient quantity, at specifi ed inter-vals, and for an indicated duration to achieve the desired therapeutic outcomes. The effectiveness of the medication in achieving the prescriber’s objectives should be reevaluated at regular inter-vals and necessary adjustments made in the dos-age, regimen, schedule, or form, or indeed, in the choice of the drug administered. Patients’ expressions of disappointment in the rate of progress or complaints of side effects to the pre-scribed drug should be evaluated and decisions made as to the continuance, adjustment, or major change in drug therapy. Before initially taking a medication, a patient should be advised of any expected side effects and of foods, bever-ages, and/or other drugs that may interfere with the effectiveness of the medication.
Through professional interaction and com-munication with other health professionals, the pharmacist can contribute greatly to patient care. An intimate knowledge of drug actions, pharma-cotherapeutics, formulation and dosage form design, available pharmaceutical products, and drug information sources makes the pharmacist a vital member of the health care team. The pharmacist is entrusted with the legal responsi-bility for the procurement, storage, control, and distribution of effective pharmaceutical products and for the compounding and fi lling of prescrip-tion orders. Drawing on extensive training and knowledge, the pharmacist serves the patient as an advisor on drugs and encourages their safe and proper use through patient counseling. The pharmacist delivers pharmaceutical services in a variety of community and institutional health care environments and effectively uses medica-tion records, patient monitoring, and assessment techniques in safeguarding the public health.
To appreciate the progress that has been made in drug discovery and development and to provide background for the study of modern drugs and pharmaceutical dosage forms, it is important to examine pharmacy’s heritage.
