The various types of tablets are described as follows.
- In addition to the medicinal agent or agents, compressed tablets usually contain a number of pharmaceutical adjuncts, including the following:
Diluents or fillers, which add the necessary bulk to a formulation to prepare tablets of the desired size.
- Binders or adhesives, which promote adhesion of the particles of the formulation, allowing a granulation to be prepared and maintaining the integrity of the final tablet.
- Disintegrants or disintegrating agents, which promote breakup of the tablets after administration to smaller particles for ready drug availability.
- Antiadherents, glidants, lubricants, or lubricating agents, which enhance the flow of the material into the tablet dies, minimize wear of the punches and dies, prevent fill material from sticking to the punches and dies, and produce tablets with a sheen.
- Miscellaneous adjuncts such as colorants and flavorants.After compression, tablets may be coated with various materials as described later. Tablets for oral, buccal, sublingual, or vaginal administration may be prepared by compression
MULTIPLY COMPRESSED TABLETS
Multiply compressed tablets are prepared by subjecting the ﬁll material to more than a single compression. The result may be a multiple-layer tablet or a tablet within a tablet, the inner tablet being the core and the outer portion being the shell . Layered tablets are prepared by initial compaction of a portion of ﬁll material in a die followed by additional ﬁll material and compression to form two-layered or three- layered tablets, depending on the number of separate ﬁlls. Each layer may contain a different medicinal agent, separated for reasons of chemi- cal or physical incompatibility, staged drug release, or simply for the unique appearance of the layered tablet. Usually, each portion of ﬁll is a different color to produce a distinctive-looking tablet. In preparation of tablets within tablets, special machines are required to place the pre- formed core tablet precisely within the die for application of surrounding ﬁll material. Examples include Norgesic Tablets (3M).
Compressed tablets may be coated with a col- ored or an uncolored sugar layer. The coating is water soluble and quickly dissolves after swallowing. The sugarcoat protects the enclosed drug from the environment and provides a barrier to objectionable taste or odor. The sugarcoat also enhances the appearance of the compressed tablet and permits imprinting of identifying manufacturer’s information. Among the disadvantages to sugarcoating tablets are the time and expertise required in the coating process and the increase in size, weight, and shipping costs. Sugarcoating may add 50% to the weight and bulk of the uncoated tablet.
Film-coated tablets are compressed tablets coated with a thin layer of a polymer capable of forming a skinlike ﬁlm. The ﬁlm is usually colored and has the advantage over sugarcoatings in that it is more durable, less bulky, and less time- consuming to apply. By its composition, the coating is designed to rupture and expose the core tabletatthedesiredlocationinthegastrointestinal tract.
A recent innovation is the gelatin-coated tablet. The innovator product, the gelcap, is a capsule- shaped 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 swal- lowing, and gelatin-coated tablets are more tam- per evident than unsealed capsules. Examples include Extra Strength Tylenol PM Gelcaps (McNeil-CPC).
Enteric-coated tablets have delayed-release features. They are designed to pass unchanged through the stomach to the intestines, where the tablets disintegrate and allow drug dissolution and absorption and/or effect. Enteric coatings are employed when the drug substance is destroyed by gastric acid or is particularly irritating to the gastric mucosa or when bypass of the stomach substantially enhances drug absorption. Examples include Ecotrin Tablets and Caplets (Smith- Kline Beecham).
BUCCAL AND SUBLINGUAL TABLETS
Buccal and sublingual tablets are ﬂat, oval tab- lets intended to be dissolved in the buccal pouch (buccal tablets) or beneath the tongue (sublin- gual tablets) for absorption through the oral mucosa. They enable oral absorption of drugs that are destroyed by the gastric juice and/or are poorly absorbed from the gastrointestinal tract. Buccal tablets are designed to erode slowly, whereas those for sublingual use (such as nitro- glycerin) dissolve promptly and provide rapid drug effects. Lozenges or troches are disc-shaped solid dosage forms containing a medicinal agent and generally a ﬂavoring substance in a hard candy or sugar base. They are intended to be slowly dissolved in the oral cavity, usually for local effects, although some are formulated for systemic absorption. An example would be Mycelex Troches (Bayer).
Chewable tablets, which have a smooth, rapid disintegration when chewed or allowed to dis- solve in the mouth, have a creamy base, usually of specially ﬂavored and colored mannitol. Chewable tablets are especially useful for administration of large tablets to children and adults who have difﬁculty swallowing solid dos- age forms. Examples include Pepcid Chewable Tablets (J & J Merck) and Rolaids Chewable Tablets (McNeil).
Effervescent tablets are prepared by compressing granular effervescent salts that release gas when in contact with water. These tablets generally contain medicinal substances that dissolve rapidly when added to water. The “bubble action” can assist in breaking up the tablets and enhancing the dissolution of the active drug. Examples include Alka Seltzer Original and Extra-Strength Tablets (Bayer) and Zantac EFFERdose (Glaxo- SmithKline).
Certain tablets, such as tablet triturates, may be prepared by molding rather than by compres- sion. The resultant tablets are very soft and soluble and are designed for rapid dissolution.
Tablet triturates are small, usually cylindrical, molded or compressed tablets containing small amounts of usually potent drugs. Today, only a few tablet triturate products are available com- mercially, with most of these produced by tablet compression. Since tablet triturates must be readily and completely soluble in water, only a minimal amount of pressure is applied during their manufacture. A combination of sucrose and lactose is usually the diluent. The few tablet triturates that remain are used sublingually, such as nitroglycerin tablets.
Pharmacists also employ tablet triturates in compounding. Forexample, triturates are inserted into capsules or dissolved in liquid to provide accurate amounts of potent drug substances.
Hypodermic tablets are no longer available in the United States. They were originally used by phy- sicians in extemporaneous preparation of paren- teral solutions. The required number of tablets was dissolved in a suitable vehicle, sterility attained, and the injection performed. The tablets
were a convenience, since they could be easily carried in the physician’s medicine bag and injec- tions prepared to meet the needs of the individual patients. However, the difﬁculty in achieving ste- rility and the availability of prefabricated inject- able products, some in disposable syringes, have eliminated the need for hypodermic tablets.
Dispensing tablets are no longer in use. They might better have been termed compounding tablets because the pharmacist used them to compound prescriptions; they were not dis- pensed as such to the patient. The tablets contained large amounts of highly potent drug substances, so the pharmacist could rapidly obtain premeasured amounts for compounding multiple dosage units. These tablets had the dangerous potential of being inadvertently dis- pensed as such to patients.
Immediate-release tablets are designed to disin- tegrate and release their medication with no special rate-controlling features, such as special coatings and other techniques.
INSTANTLY DISINTEGRATING OR DISSOLVING TABLETS
Instant-release tablets (rapidly dissolving tablets, or RDTs) are characterized by disintegrating or dissolving in the mouth within 1 minute, some within 10 seconds (e.g., Claritin Reditabs [lorata- dine], Schering). Tablets of this type are desig- ned for children and the elderly or for any patient who has difﬁculty in swallowing tablets. They liq- uefy on the tongue, and the patient swallows the liquid. A number of techniques are used to pre- pare these tablets, including lyophilization (e.g., Zydis, R.P. Scherer), soft direct compression (e.g., Wow-Tab, Yamanouchi-Shaklee Pharma), and other methods (e.g., Quicksolv, Janssen). These tablets are prepared using very water- soluble excipients designed to wick water into the tablet for rapid disintegration or dissolution. They have the stability characteristics of other solid dosage forms.
The original fast-dissolving tablets were molded tablets for sublingual use. They generally consisted of active drug and lactose moistened with an alcohol–water mixture to form a paste.
The tablets were then molded, dried, and packaged. For use, they were simply placed under the tongue to provide a rapid onset of action for drugs such as nitroglycerin. Also, they have been used for drugs that are destroyed in the gastrointestinal tract, such as testosterone, administered sublingually for absorption to mini- mize the ﬁrst-pass effect.
These RDTs are more convenient to carry and administer than an oral liquid. They are gen- erally packaged in cards or bubble-type packag- ing with each individual tablet in its own cavity. As these tablets are often soft, the backing is peeled back to reveal the tablet where it is then removed, as opposed to attempting to press the tablet through the backing material as is com- mon with standard compressed tablets. There are no standards that deﬁne an RDT, but one possibility is dissolution in the mouth within approximately 15 to 30 seconds; anything slower would not be categorized as rapidly dissolving.
Notwithstanding these advantages, there are a number of disadvantages and difﬁculties asso- ciated with formulating RDTs, including drug loading, taste masking, friability, manufacturing costs, and stability of the product.
Drug loading is incorporation of the drug into the dosage form. Some RDTs are made as blanks to which a drug is post-loaded, or added after the blank is made. Generally the drug is in solu- tion, often in an organic solvent (alcohol), and is added to the tablet, after which the solvent evaporates. It is also possible for the drug to be added as a dry powder electrostatically at this stage. Most drugs, however, are incorporated into the tablets during manufacturing.
Taste masking poses numerous challenges for RDTs. Since the drug product dissolves in the mouth, any taste of the drug must be covered, either by a ﬂavoring technique or by microencap- sulation or nanoencapsulation. The product also should not be gritty, which necessitates very small particle sizes if microencapsulation is used.
Friability is an inherent problem in RDTs. For a product to dissolve instantly, it may be quite friable. Making it more ﬁrm and less fria- ble may increase dissolution time. A balance generally must be achieved between friability and the speed of dissolution.
The ﬁrst entry into the RDT ﬁeld was the Zydis delivery system. The tablets are prepared by foaming a mixture of gelatin, sugar or sugars, drug, and any other components and by pouring the foam into a mold. The mold also serves as the unit dose dispensing package. The foam is lyophilized , and the tablets in the mold are packaged. This system is the fastest disinte- grating system on the market, as the tablets will dissolve on the tongue in a matter of a few seconds. One disadvantage of this method is that taste masking can be a problem, since the drug is incorporated during the formation of the tablet itself. Another difﬁculty is that these tablets are sometimes difﬁcult to remove from the packag- ing, since they are soft and one should not press on the dosage unit to remove it but should peel off the material, exposing the tablet in its mold.
Claritin (loratadine) rapidly disintegrating tablets (Reditabs, Schering Corporation) contain 10 mg of micronized loratadine in a base con- taining citric acid, gelatin, mannitol, and mint ﬂavor formed with the Zydis technology. It disin- tegrates within seconds after being placed on the tongue, with or without water. Claritin Reditabs have been shown to provide at least equivalent pharmacokinetic parameters to those of tradi- tional tablets; in some cases, the Reditabs pro- vided greater maximum concentration (Cmax) and
area under the curve values. Claritin Reditabs
are blister-packaged tablets that should be stored in a dry place at 2°C to 25°C. They should be used within 6 months of opening the protective laminated foil pouch containing the blister cards; each foil pouch contains one blister card con- taining 10 individually sealed tablets (1). Other commercial products using this technology include the Maxalt-MLT (Merck), Zofran ODT (GlaxoSmithKline), Zyprexa Zydis (Eli Lilly) tablets, and Tylenol Meltaways (McNeil). It should be noted that the Clarinex Reditabs (Desloratadine, Schering) use a different formu- lation principle, despite the same dosage form designation. The excipients consist of mannitol, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, magnesium stearate, butylated methacrylate copolymer, crospovi- done, aspartame, citric acid, sodium bicarbon- ate, colloidal silicon dioxide, ferric oxide red, and tutti frutti ﬂavoring (2).
Another method of preparation is using standard tableting technology with a composition that will enhance ﬂuid uptake and tablet disintegration and dissolution. For example, superdisintegrants incorporated with a small quantity of efferves- cent material will lead to intermediately fast dis- integration. The tablets are compressed a little thinner than standard tablets to allow for a larger surface area exposed to the saliva in the mouth. Upon placement in the mouth, the disintegrant
starts wicking water into the tablet. The effervescent materials start dissolving and aid in the breakup. This continues until the tablet has disintegrated.
An example product is the Dimetapp ND Orally Disintegrating Tablet (Nondrowsy Allergy Tablets). These tablets contain loratadine 10 mg in a vehicle of artiﬁcial and natural ﬂavor, aspar- tame, citric acid, colloidal silicon dioxide, corn syrup solids, crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, modiﬁed food starch, and sodium bicarbonate (3).
One product using the DuraSolv and OraSolv technologies by Cima Labs is Tempra Quicklets containing acetaminophen 80 mg. These tablets also contain aspartame, citric acid, D&C Red No. 27 Lake, FD&C Blue No. 1 Lake, ﬂavor, magnesium stearate, mannitol, potassium car- bonate, silicon dioxide, and sodium bicarbonate. They are somewhat slower than the Zydis tablet, taking about 30 to 45 seconds, unless some tongue pressure is used. These tablets come in a ﬁrm molded plastic package to prevent break- age (4). Other commercial products using the same technology include the Alavert (Wyeth Consumer Healthcare), NuLev FasTabs(Schwarz Pharma), Symax FasTabs (Capellon), Remeron SolTabs (Organon Teknika), Triaminic Softchews (Novartis Pharmaceutical), Abilify Discmelt (Bristol-Myers Squibb), Tylenol Meltaways (McNeil), and the Zomig Rapidmelt (Zeneca Pharmaceuticals).
The Flashtab technology by Ethypharm is used in Excedrin QuickTabs and an example of the Wowtab technology by Yamanouchi Pharma is the Benadryl Fastmelt.
Extended-release tablets (sometimes called controlled-release tablets) are designedto release their medication in a predetermined manner over an extended period. They are discussed in Chapter 9.
Vaginal tablets, also called vaginal inserts, are uncoated, bullet-shaped or ovoid tablets inserted into the vagina for local effects. They are pre- pared by compression and shaped to ﬁt snugly on plastic inserter devices that accompany the product. They contain antibacterials for the treatment of nonspeciﬁc vaginitis caused by Haemophilus vaginalis or antifungals for the treatment of vulvovaginitis candidiasis caused by Candida albicans and related species.
Source : Solid Dosage Forms and Solid Modified Release Drug Delivery System