The development of a new chemical entity (NCE) requires the testing of its biological activity at various stages of development. For systemically acting drugs, animal studies are carried out at early stages of development using parenteral administration of a solubilized form of the drug. As drug development proceeds to later stages, human clinical studies are preferred with an orally administered dosage form that is both simple to formulate and provides adequate bioavailability.
Preferred drug product (DP) dosage form choices are determined based on the drug substance’s (DS’s) physicochemical properties, patient and disease state constraints and preferences, dose, manufacturability, and commercial factors such as other therapeutic options available to the patient.
An oral tablet dosage form is usually the most preferred dosage form because of patient convenience and acceptance. Most drugs are formulated in tablet dosage forms. Tablets are available in a wide variety of shapes, sizes, colors, and surface markings.
Types of tablets
Depending on the physicochemical properties of the drug, site and extent of drug absorption in the gastrointestinal (GI) tract, stability to heat, light, or moisture, biocompatibility with other ingredients, solubility, and dose, the following types of tablets are commonly formulated.
1. Swallowable tablets
The most common types of tablets are swallowed whole. These tablets disintegrate and release their contents in the GI tract.
2. Effervescent tablets
These tablets are formulated to allow dissolution or dispersion in water prior to administration and should not be swallowed whole. In addition to the DS, these tablets contain sodium carbonate or bicarbonate and an organic acid such as tartaric acid. In the presence of water, these additives react, liberating carbon dioxide, which acts as a disintegrator and produces effervescence. The drug is released into the aqueous medium as a solution, if it is highly soluble, or suspension. Ingestion of a dissolved or finely dispersed drug provides a rapid rate of drug absorption. Therefore, effervescent tablets can be suitable for acute conditions that require immediate relief, such as pain and gastric acidity. For example, cephalon’s fentanyl effervescent tablet can be used to reduce the intensity of breakthrough pain in cancer patients.
3. Chewable tablets
Chewable tablets are used when a faster rate of dissolution and/or buccal absorption is desired. Chewable tablets consist of the drug dispersed throughout a saccharide base that provides mild sweetness. Flavors, sweeteners, and colors are also added to chewable tablets to improve palatability and organoleptic appeal. The drug is released from the dosage form by physical disruption associated with chewing and dissolution in the fluids of the oral cavity, and the presence of a effervescent material. For example, some antacid tablets can be chewed to obtain quick indigestion relief. Chewable tablets are typically prepared by compression and usually contain mannitol or sorbitol as saccharide, mildly sweet, fillers. Mannitol is sometimes preferred as a chewable base diluent, because it has a pleasant cooling sensation in the mouth due to negative heat of dissolution and can mask the taste of some objectionable medicaments.
4. Buccal and sublingual tablets
Buccal and sublingual tablets dissolve in the cheek pouch (buccal) or under the tongue (sublingual). Buccal or sublingual route of drug absorption bypasses hepatic metabolism, often referred to as the first-pass effect on oral administration, and is preferred for low dose drugs that have extensive hepatic metabolism. Sublingual administration also allows rapid drug absorption, which may be critical in cases such as nitroglycerin for chronic heart failure. Other examples include isoprenaline sulfate (bronchodilator), glyceryl trinitrate (vasodilator), and testosterone tablets. These tablets are usually small and flat, do not contain a disintegrant, and are intended for dissolution in the local fluids.
Lozenges are slow dissolving compressed tablets that do not contain a disintegrant. Some lozenges contain antiseptics (e.g., benzalkonium) or antibiotics for local effects in the mouth. Lozenges are also used for systemic effect, such as those containing vitamin supplements. Lozenges are palatable and organoleptically appealing by the addition of flavors, sweeteners, and colors.
6. Coated tablets
Most tablets are coated for one or more of the following reasons:
• To prevent decomposition of drugs sensitive to air (oxygen), light, or humidity
• To minimize the unpleasant taste of certain drugs that may come during partial dissolution of the drug in buccal fluids during absorption
• To improve swallowability and palatability by increasing surface smoothness in the mouth
• To provide visual appeal and consistency, smooth surface texture, and uniform distribution of color
• To serve as anticounterfeiting medium by incorporating tracer compounds in the coating material
• To allow containment of highly potent compounds in the core of the tablet and, thus, avoid exposure to personnel handling of the tablets.
Coating is not used on buccal, sublingual, chewable, effervescent, or dispersible tablets to avoid any delay in drug release due to the time required for the rupture or dissolution of the coating material.
7. Enteric coated tablets
GI fluid pH increases progressively from acidic to basic from the stomach through the intestines to the colon. The changes in GI pH can be utilized to release a drug at a particular physiological location in the GI tract. In particular, oral solid dosage forms can be coated with a polymer that is insoluble at the acidic stomach pH and soluble at basic intestinal pH. Such polymers are known as enteric polymers and such coatings are termed enteric coatings.
Enteric-coated tablets are the tablets coated with enteric polymers. Complete coating of the tablet with these polymers allows the polymer to form a barrier between the core of the tablet and the surrounding aqueous medium. Thus, the enteric-coated tablet remains insoluble in the low pH environment of the stomach, but dissolves readily on passage into the small intestine with its elevated pH.
Enteric coating is used to minimize irritation of the gastric mucosa by certain drugs and/or protect sensitive drugs against decomposition in the acidic environment of the stomach. For example, aspirin produces less gastric bleeding when formulated as enteric-coated sustained-release (SR) tablets than conventional immediate release dosage forms.
8. Immediate release tablets
Most tablets (discussed earlier) are immediate release (IR) tablets, that is, they make all the drugs available to the dissolution medium immediately on coming in contact with the aqueous medium. The drug dissolves at a rate determined by the composition of the dissolution medium (such as pH) and physicochemical properties of the drug (such as solubility and particle size).
9. Controlled release tablets
In contrast to the IR tablets, certain dosage forms, such as controlled-release (CR) or extended-release (XR) tablets, are designed to control or extend, respectively, the rate at which drug dissolves in the aqueous medium. Thus, CR tablets reduce the rate of drug release to a slow, controlled rate, which is typically zero order. XR tablets, on the other hand, extend the duration of drug release by slowing down the rate of drug release but may not have control on the rate (i.e., may not provide zero-order kinetics of drug release).
CR or XR tablets are sometimes also called SR tablets. CR tablets can reduce dosing frequency, increase patient compliance, and may reduce side effects of certain drugs. The rate-controlling feature of the CR tablets could be either the matrix or the film coating. Coformulating or mixing drugs with water-insoluble polymers prepare matrix tablets. A slow dissolving polymer matrix, such as high molecular weight HPMC, can be used to prepare SR tablets of highly water-soluble drugs.
On coming in contact with the aqueous dissolution medium, the core tablet dissolves by surface erosion, and the rate of surface erosion is controlled by the rate of dissolution of the polymer matrix. For example, metformin hydrochloride XR tablets (Glucophage XR tablets®) are matrix tablets.