Pharmaceutical Dosage Forms-3 Lecture 3 PDF

Department of Pharmaceutics & Pharmaceutical Technology PHARMACEUTICAL DOSAGE FORMS-3 (CPT 505) For 3rd Level Pharm-D Clinical Program Solid Dosage Forms By Dr. Mohamed Abd El-Hamid Ismail Lecturer of pharmaceutics Department of...

Department of Pharmaceutics & Pharmaceutical Technology PHARMACEUTICAL DOSAGE FORMS-3 (CPT 505) For 3rd Level Pharm-D Clinical Program Solid Dosage Forms By Dr. Mohamed Abd El-Hamid Ismail Lecturer of pharmaceutics Department of Pharmaceutics & Pharmaceutical Technology Lecture 3 By Dr. Mohamed Abd El-Hamid Ismail Lecturer of pharmaceutics C-Solid Dosage Forms 3 III-Tablets 10/16/2024 Overview In this chapter the following points will be discussed: an overview/description of the various types of solid-dosage forms and the rationale for their use formulation strategies for solid-dosage forms an overview/description of the methods of manufacture of solid-dosage forms, including post-manufacture processes (e.g. coating) the advantages and disadvantages of the different methods that are used to manufacture solid-dosage forms a detailed description of the excipients used in the formulation and manufacture of solid dosage forms.  Solid-dosage forms encompasses the largest category of dosage forms that are clinically used. There are several types of tablet solid dosage form that are designed to optimize the absorption rate of the drug, increase the ease of KeyPoints administration by the patient, control the rate and site of drug absorption and mask the taste of a therapeutic agent. The formulation of tablets involves the use of several components, each of which is present to facilitate the manufacture or to control the biological performance of the dosage form. There are three main methods by which tablets may be manufactured: (1) Wet granulation; (2) dry granulation (slugging or roller compaction); and (3) direct compression; There are advantages and disadvantages associated with the use of these methods. Introduction Solid-dosage forms broadly encompass two types of formulation, namely tablets and capsules. It has been estimated that solid-dosage forms constitute circa 90% of all dosage forms used to provide systemic administration of therapeutic agents. This highlights the importance of these dosage forms in the treatment and management of disease states. 16 October 2024 Introduction  Definition  Tablets are solid dosage forms usually prepared with the aid of suitable pharmaceutical excipients.  They may vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture.  Most tablets are used in the oral administration of drugs.  Many of these are prepared with colorants and coatings of various types. 16 October 2024 Advantages and disadvantages of tablets as dosage forms As stated in the introduction, tablets are the most popular dosage form used today and therefore there are several advantages associated with their use. However it is also important to highlight the disadvantages associated with their use. Advantages Tablets are convenient to use and are an elegant dosage form. A wide range of tablet types is available, offering a range of drug release rates and durations of clinical effect. Tablets may be formulated to offer rapid drug release or controlled drug release, the latter reducing the number of daily doses required (and in so doing increasing patient compliance). Tablets may be formulated to release the therapeutic agent at a particular site within the gastrointestinal tract to reduce side effects, promote absorption at that site and provide a local effect (e.g. ulcerative colitis). This may not be easily achieved by other dosage forms that are administered orally. Advantages and disadvantages of tablets as dosage forms Advantages Tablets may be formulated to contain more than one therapeutic agent (even if there is a physical or chemical incompatibility between each active agent). Moreover, the release of each therapeutic agent may be effectively controlled by the tablet formulation and design. With the exception of proteins, all classes of therapeutic agents may be administered orally in the form of tablets. It is easier to mask the taste of bitter drugs using tablets than for other dosage forms, e.g. liquids. Tablets are generally an inexpensive dosage form. Tablets may be easily manufactured to show product identification, e.g. exhibiting the required markings on the surface. The chemical, physical and microbiological stability of tablet dosage forms is superior to other dosage forms. Advantages and disadvantages of tablets as dosage forms Disadvantages The manufacture of tablets requires a series of unit operations and therefore there is an increased level of product loss at each stage in the manufacturing process. The absorption of therapeutic agents from tablets is dependent on physiological factors, e.g., gastric emptying rate and shows interpatient variation. The compression properties of certain therapeutic agents are poor and may present problems in their subsequent formulation and manufacture as tablets. The administration of tablets to certain groups, e.g., children and the elderly, may be problematic due to difficulties in swallowing. These problems may be overcome by using effervescent tablet dosage forms. Different Types of Tablets The widespread use of tablets has been achieved as a result of their convenience and also the diversity of tablet types. Examples of tablet types available include: (1) conventional compressed tablets; (2) multiple compressed tablets; (3) enteric-coated tablets; (4) sugar-coated tablets; (5) film-coated tablets; (6) chewable tablets; (7) effervescent tablets; (8) buccal and sublingual tablets; and (9) vaginal tablets. 1-Conventional compressed tablets These tablets are designed to provide rapid disintegration and hence rapid drug release and represent a significant proportion of tablets that are clinically used. The manufacture of these tablets involves the compression of granules or powders (both containing drug) into the required geometry. Following ingestion, the tablets will disintegrate within the gastrointestinal tract (stomach), allowing the drug to dissolve in the gastric fluid and, ultimately, be absorbed systemically. 2-Multiple compressed tablets These are tablets that are composed of at least two layers. Typically there are two designs of multiple compressed tablets: (A) compression coated; and (B) multiple-layered. In the former design the first layer is formed by a relatively light compression of the drug containing powder mix/granules. The next layer is then formed by compression of the powder/granule mix (containing drug) on top of the lightly compressed first layer. Additional layers are formed in a similar fashion. In the second approach the initial layer is prepared by light compression (as described above), removed and located in a second tablet press. The granules/powders of the second coat are fed into the press and allowed to form a constant mass around the surface (and edges) of the pressed tablet prior to compression to form the finished product. It is, of course, possible to prepare tablets containing more than two layers although, in so doing, the complexity of the manufacturing process is dramatically increased. A: a core of one drug and a shell of another. B: a layered tablet of two drugs. 2-Multiple compressed tablets There are several applications of the use of multiple compressed tablets, including: the separation of drugs into separate layers that may be incompatible when formulated as a (single-layer) conventional tablet the delivery of therapeutic agents at different rates or to different sites within the gastrointestinal tract from a single tablet. The dissolution of the layers of the tablet or, indeed, the dissolution/diffusion of the drug from the layer may be controlled by the inclusion of polymeric excipients the production of tablets that are coated. This is important in cases where the drug has a bitter taste or where the drug is irritant to the stomach (e.g. non-steroidal anti-inflammatory drugs) or is chemically unstable under acidic conditions. A: a core of one drug and a shell of another. B: a layered tablet of two drugs. 3-Enteric-coated tablets These are tablets that are coated with a polymer that does not dissolve under acidic conditions (i.e. the stomach) but does dissolve under the more alkaline conditions of the small intestine. Enteric polymers are primarily employed as coatings of conventional tablet dosage forms and, by inhibiting the dissolution of the therapeutic agent within the stomach, offer protection against possible drug degradation (e.g., erythromycin) or irritation of the gastric mucosa (e.g., non- steroidal anti-inflammatory drugs). Following dissolution of the coating, the tablet will disintegrate, and the drug will dissolve in the gastric fluids (thereby facilitating absorption). Examples of polymers that are used for this purpose include: (1) cellulose actetate phthalate/cellulose acetate butyrate; Dissolution of the polymer occurs in solutions where the pH 6. (2) hydroxypropylmethyl cellulose succinate; Dissolution of this polymer occurs within the intestine, as it is insoluble in the stomach. (3) Methacrylic acid co-polymers (Eudragit). which is soluble in the intestinal fluid from pH 5.5 - 7. 4-Sugar-coated tablets These are conventional tablets that have been coated with a concentrated sugar solution to improve the appearance of the formulation and/or to mask the bitter taste of the therapeutic agent. The use of sugar coatings has dramatically decreased due to the advent of film-coated tablets (as a result of the improved mechanical properties of the latter coating). 5-Film-coated tablets These are conventional tablets that have been coated with a polymer or a mixture of polymers (and, when required, a plasticizer to render the coating flexible). Film coatings show improved mechanical properties when compared to sugar coatings and, furthermore, film coatings may be deposited over embossed markings on the tablet surface. Film coatings are generally less elegant than sugar coatings. Examples of polymers that are used to film-coat tablets (and which dissolve in the stomach to enable tablet disintegration and drug dissolution) include: hydroxypropylmethylcelluose hydroxypropylcellulose Eudragit E100 5-Film-coated tablets In addition to improving the appearance of conventional tablets, film coatings are employed to control the rate and duration of drug release or to target drug release to certain regions of the gastrointestinal tract, e.g. the colon. If the film coating is insoluble, the tablet will retain its shape during transit along the gastrointestinal tract. Drug release occurs by diffusion through the insoluble coating and subsequent partitioning into the gastrointestinal fluids. Examples of polymers that may be used for this purpose include: (1) ethylcellulose; and (2) Eudragit RS and RL. 6-Chewable tablets As indicated by the name, these tablets are chewed within the buccal cavity prior to swallowing. The main applications for this dosage form are: for administration to children and adults who have difficulty in swallowing conventional tablets antacid formulations in which the size of the tablet is normally large, and the neutralization efficacy of the tablet is related to particle size within the stomach. Conversely, chewable tablets are not conventionally used if the drug has issues regarding taste acceptability. 7-Effervescent tablets Effervescent tablets are added to aqueous solutions where they will rapidly disintegrate and produce either a drug suspension or an aqueous solution. The disintegration of the tablet is due to a chemical interaction that occurs between two components: (1) An organic acid (e.g. citric acid); and (2) sodium bicarbonate in the presence of water. The evolution of carbon dioxide from this reaction results in tablet disintegration. The patient then consumes the solution/suspension. The main advantage of the use of effervescent tablets is the production of a dosage form from which the therapeutic agent is more rapidly absorbed than from alternative solid-dosage forms (e.g. conventional tablets). Conversely, the main disadvantages of this type of dosage form are the possible (un)availability of water and the need to package these tablets in moisture-impermeable packaging (typically aluminium foil), to inhibit the interaction between the acid and sodium bicarbonate due to the presence of environmental moisture. 8-Buccal and sublingual tablets Buccal and sublingual tablets are dosage forms that are held within the oral cavity and slowly dissolve; the drug is absorbed across the buccal mucosa to produce a systemic effect. The type of tablet dictates the location within the oral cavity. Accordingly buccal tablets are positioned between the cheek and the gingiva whereas sublingual tablets are positioned underneath the tongue. These tablets are employed to achieve either rapid absorption into the systemic circulation (e.g. glyceryl trinitrate sublingual tablets) or, alternatively, to enable systemic drug absorption in situations where oral drug delivery is inappropriate, e.g. nausea. Drug absorption across the buccal mucosa avoids first-pass metabolism. Typically buccal and sublingual tablets should be formulated to dissolve slowly in vivo (and not disintegrate) and to be retained at the site of application and should not contain components that stimulate the production of saliva. 9-Vaginal tablets These are ovoid-shaped tablets that are inserted into the vagina (using a special inserter). Following insertion, retention and slow dissolution of the tablet occur, releasing the therapeutic agent to provide the local pharmacological effect (e.g. for the treatment of bacterial or fungal infection). Vaginal tablets may also be used to provide systemic absorption of therapeutic agents. In a similar fashion to buccal/sublingual tablets, it is important that dissolution, and not disintegration, of the tablet occurs in vivo, as disintegration will reduce tablet retention within the vagina. 10-Gelatin-Coated Tablets Gelcap is a capsule-shaped (Caplet) gelatin coated compressed tablet that allows the coated product to be about one-third smaller than a capsule filled with an equivalent amount of powder. The gelatin coating facilitates swallowing. According to the drug release characteristics or rate: 1-Immediate Release Tablets (IR Tablets) are designed to disintegrate and release their medication with no special rate- controlling features, such as special coatings and other techniques. 2-Modified Release Tablets (MR Tablets) or Controlled Release Tablets (CR Tablets) include: Sustained/Extended Release (SR/ XR Tablets) or Delayed Release (Enteric Coated Tablets) 3- Rapidly Disintegrating or Dissolving Tablets (RD Tablets), Rapid-release Tablets or Oro-Dispersible Tablets (ODT) are characterized by disintegrating or dissolving in the mouth within 1 minute, some within 10 seconds. Tablets of this type are designed for children and the elderly or for any patient who has difficulty in swallowing tablets. They liquefy on the tongue, and the patient swallows the liquid. Tips The different types of solid-dosage forms are designed to provide flexible platforms for the delivery of therapeutic agents to the gastrointestinal tract. Coating tablets with polymers offers opportunities for the release of the therapeutic agent at particular regions within the gastrointestinal tract, e.g. the small intestine, colon. Effervescent tablets are used to enhance the absorption of poorly soluble drugs. The use of multilayered tablets has decreased in recent years.