An appropriate manufacturing process and testing regimen help ensure that a dosage form can meet the appropriate quality attributes for the intended route of administration.

In some cases, testing for heavy metal impurities is appropriate. (Official 1-Dec-2015)

Aerosols are dosage forms packaged under pressure and contain therapeutic agent(s) and a propellant that are released upon actuation of an appropriate valve system. Upon actuation of the valve system, the drug substance is released as a plume of fine particles or droplets. Only one dose is released from the preparation upon actuation of a metered valve. In the case of topical products and depending on the nature of the drug substance and the conditions being treated, actuation of the valve may result in a metered release of a controlled amount of the formulation or the continuous release of the formulation as long as the valve is depressed.

The aerosol dosage form refers only to those products packaged under pressure that release a fine mist of particles or droplets when actuated (see Glossary). Other products that produce dispersions of fine droplets or particles will be covered in subsequent sections (e.g., Powders and Sprays).

Capsules are solid dosage forms in which the drug substance and/or excipients are enclosed within a soluble container or shell or coated on the capsule shell. The shells may be composed of two pieces (a body and a cap), or they may be composed of a single piece. Two-piece capsules are commonly referred to as hard-shell capsules, and one-piece capsules are often referred to as soft-shell capsules. This two-piece and one-piece capsule distinction, although imprecise, reflects differing levels of plasticizers in the two compositions and the fact that one-piece capsules typically are more pliable than two-piece capsules.

The shells of capsules are usually made from gelatin. However, they may also be made from cellulose polymers or other suitable material. Most capsules are designed for oral administration. When no deliberate effort has been made to modify the drug substance release rate, capsules are referred to as immediate-release.

(See Emulsions.)

An emulsion is a dispersed colloidal system consisting of two immiscible liquid phases generally stabilized with one or more suitable agents.

Typical pharmaceutical emulsions are prepared from immiscible aqueous and organic (oil) liquids. Complex multiple-phase systems may exist in an emulsion. Whether the organic or the aqueous phase is the dispersed phase depends on the volumes of the two phases, the emulsifier chosen, and the method of preparation. When an oil phase is dispersed in an aqueous phase, the emulsion is termed an oil in water (O/W) emulsion and water is referred to as the continuous phase. When water is dispersed in oil, the emulsion is referred to as a water in oil (W/O) emulsion. Emulsions have dispersed phases typically ranging from 0.1 to 100 µm. Emulsions are opaque while microemulsions are usually transparent or translucent. Microemulsions have dispersed phases less than 0.1 µm.

Emulsions may exhibit three types of instability: flocculation, creaming, and coalescence. Flocculation describes the process by which the dispersed phase comes out of suspension in the form of flakes. Coalescence is another form of instability—small droplets within the media continuously combine to form progressively larger droplets. Emulsions can also undergo creaming, where one of the phases migrates to the top (or the bottom, depending on the relative densities of the two phases) of the emulsion. To prevent flocculation, creaming, and coalescence of the emulsions, manufacturers commonly add surfactants, pH-modifying agents, or emulsifying agents to increase the stability of emulsions so that the emulsion does not change significantly with time.

Emulsions are widely used as pharmaceutical dosage forms. Oral emulsions have been prepared to improve taste, solubility, stability, or bioavailability. Emulsions for topical administration are referred to as creams, lotions, and sometimes ointments. Parenteral emulsions have been used for anaesthetics, parenteral nutrition, and to deliver poorly water-soluble drugs.

Films are thin sheets that are placed in the oral cavity. They contain one or more layers. A layer may or may not contain the drug substance. Typically, these thin sheets are formed by casting or extrusion which results in a dispersion of the components through the film. Films are classified by the site of application. “Oral films” can be formulated to deliver medication to the mouth such as oral hygiene products or to deliver medication to the gastrointestinal tract for absorption. “Buccal films” and “sublingual films” are formulated to facilitate absorption through the proximal mucosal membranes avoiding first pass metabolism or degradation in the gastrointestinal tract and providing a quick onset of action.

Films can be formulated with edible polymers such as pullulan or with water-soluble polymers such as modified cellulose, edible gums, and copolymers. The dissolution rate of the film is controlled to facilitate incorporation of the medication into saliva or for absorption by the proximal mucosa. These films must be substantial enough to maintain their integrity during manufacture and packaging, and permit handling by the patient. Because of the rapid dissolution, taste and mouth feel are important considerations.

Foams are preparations that comprise gas bubbles distributed in a liquid. The liquid contains the drug substance and suitable excipients. Medicated foams may be packaged in pressurized containers or in other special dispensing devices. For medicated foams dispensed from nonpressurized containers, the use of mechanical force is required to generate the foam. Foams are intended for application to the skin or mucous membranes. The medicated foam is formed at the time of application. Surfactants are used to ensure the distribution of the gas in the liquid and to stabilize the foam. Medicated foams have a semisolid consistency and can be formulated to quickly break down into liquid or to remain as foam to ensure prolonged contact.

Medicated foams intended to treat severely injured skin or open wounds must be sterile.

Medical gases are products that are administered directly as a gas. A medical gas has a direct pharmacological action or acts as a diluent for another medical gas. Gases used as excipients for administration of aerosol products, as an adjuvant in packaging, or produced by other dosage forms, are not included in this definition.

Gels are semisolids consisting either of suspensions of small inorganic particles or of organic molecules interpenetrated by a liquid. Jellies are a type of gel that typically have a higher water content. Gels can be classed either as single-phase or two-phase systems.

A two-phase gel consists of a network of small discrete particles (e.g., Aluminum Hydroxide Gel or Psyllium Hemicellulose). These gels may be thixotropic, forming semisolids on standing and becoming less viscous on agitation. They should be shaken before use to ensure homogeneity and should be so labeled.

Single-phase gels consist of organic macromolecules uniformly distributed throughout a liquid in such a manner that no apparent boundaries exist between the dispersed macromolecules and the liquid. Single-phase gels may be made from natural or synthetic macromolecules (e.g., Carbomer, Hypromellose, or Starch) or natural gums (e.g., Tragacanth). The latter preparations are also called mucilages. Although these gels are commonly aqueous, alcohols and oils may be used as the continuous phase.

Gels can be administered by the topical or mucosal routes. In veterinary medicine, gels can be administered via mammary infusion.

Granules are solid dosage forms that are composed of agglomerations of smaller particles. These multicomponent compositions are prepared for oral administration and are used to facilitate flexible dosing regimens as granules or as suspensions, address stability challenges, allow taste masking, or facilitate flexibility in administration (for instance, to pediatric patients, geriatric patients, or animals). Granular dosage forms may be formulated for direct oral administration and may facilitate compounding of multiple drug substances by allowing compounding pharmacists to blend various granular compositions in the retail or hospital pharmacy. More commonly, granules are reconstituted to a suspension by the addition of water or a supplied liquid diluent immediately prior to delivery to the patient. Effervescent granules are formulated to liberate gas (carbon dioxide) upon addition of water. Common examples of effervescent granules include antacid and potassium supplementation preparations. Common therapeutic classes formulated as granule dosage forms include antibiotics, certain laxatives (such as senna extract products), electrolytes, and various cough and cold remedies that contain multiple drug substances.

Medicated gum is a pliable dosage form that is designed to be chewed rather than swallowed. Medicated gums release the drug substance(s) into the saliva. Medicated gums can deliver therapeutic agents for local action in the mouth or for systemic absorption via the buccal or gastrointestinal routes (e.g., nicotine or aspirin). Most gums are manufactured using the conventional melting process derived from the confectionary industry or alternatively may be directly compressed from gum powder. Medicated gums are formulated from insoluble synthetic gum bases such as polyisoprene, polyisobutylene, isobutyleneisoprene copolymer, styrene butadiene rubber, polyvinyl acetate, polyethylene, ester gums, or polyterpenes. Plasticizers and softeners such as propylene glycol, glycerin, oleic acid, or processed vegetable oils are added to keep the gum base pliable and to aid in the incorporation of the drug substance(s), sweeteners, and flavoring agents. Sugars as well as artificial sweeteners and flavorings are incorporated to improve taste, and dyes may be used to enhance appearance. Some medicated gums are coated with magnesium stearate to reduce tackiness and improve handling during packaging. A preservative may be added.

Implants are long-acting dosage forms that provide continuous release of the drug substance often for periods of months to years. They are administered by the parenteral route. For systemic delivery they may be placed subcutaneously, or for local delivery they can be placed in a specific region in the body (e.g., in the sinus, in an artery, in the eye, in the brain, etc.).

Several types of implants are available. Pellet implants are small, sterile, solid masses composed of a drug substance with or without excipients. They are usually administered by means of a suitable special injector (e.g., trocar) or by surgical incision. Release of the drug substance from pellets is typically controlled by diffusion and dissolution kinetics. The size of the pellets and rate of erosion will influence the release rate, which typically follows first-order kinetics. Drug substance release from pellets for periods of 6 months or more is possible.

Resorbable microparticles are a type of implant that provides extended release of a drug substance over periods varying from a few weeks to months. They can be administered subcutaneously or intramuscularly for systemic delivery, or they may be deposited in a desired location in the body for site-specific delivery. Injectable resorbable microparticles (or microspheres) generally range from 20 to 100 µm in diameter. They are composed of a drug substance dispersed within a biocompatible, bioresorbable polymeric excipient (matrix). Poly(lactide-co-glycolide) polymers have been used frequently. These excipients typically resorb by hydrolysis of ester linkages. The microparticles are administered by suspension in an aqueous vehicle followed by injection with a conventional syringe and needle. Release of the drug substance from the microparticles begins after physiological fluid enters the polymer matrix, dissolving some of the drug substance that is then released by a diffusion-controlled process. Drug release also can occur as the matrix erodes.

Polymer implants can be formed as a single-shaped mass such as a cylinder. The polymer matrix must be biocompatible (see The Biocompatibility of Materials Used in Drug Containers, Medical Devices, and Implants 1031), but it can be either biodegradable or nonbiodegradable. Shaped polymer implants are administered by means of a suitable special injector. Release kinetics are typically not zero-order, but zero-order kinetics are possible. Drug substance release can be controlled by the diffusion of the drug substance from the bulk polymer matrix or by the properties of a rate-limiting polymeric membrane coating. Polymer implants are used to deliver potent small molecules like steroids (e.g., estradiol for cattle) and large molecules like peptides [e.g., luteinizing hormone-releasing hormone (LHRH)]. Example durations of drug substance release are 2 and 3 months for biodegradable implants and up to 3 years for nonbiodegradable implants. An advantage of biodegradable implants is that they do not require removal after the release of all drug substance content. Nonbiodegradable polymer implants can be removed before or after a drug substance release is complete or may be left in situ. An implant can have a tab with a hole in it to facilitate suturing it in place (e.g., for an intravitreal implant for local ocular delivery). Such implants may provide therapeutic release for periods as long as 2.5 years.

Drug substance-eluting stents combine the mechanical effect of the stent to maintain arterial patency with the prolonged pharmacologic effect of the incorporated drug substance (to reduce restenosis, inhibit clot formation, or combat infection). As an example, a metal stent can be coated with a nonbiodegradable or biodegradable polymer-containing drug substance. The resultant coating is a polymeric matrix that controls the extended release of the drug substance.

In veterinary medicine, drug substance(s) in pellets may be implanted subcutaneously in the animal's ear (cattle).

(See Emulsions, Powders, Solutions, and Suspensions.)

Injections are not treated as a dosage form in this chapter. Chapter 1 provides quality and other information about injectable products. Information on specific dosage form terminology can be found in the Glossary. For appropriate injection nomenclature, see Nomenclature 1121.

Inserts are solid dosage forms that are inserted into a naturally occurring (nonsurgical) body cavity other than the mouth or rectum (see Suppositories). The drug substance in inserts is delivered for local or systemic action. Vaginal inserts are usually globular or oviform and weigh about 5 g each. Inserts intended to dissolve in vaginal secretions are usually made from water-soluble or water-miscible vehicles such as polyethylene glycol or glycerinated gelatin.

As a dosage form, a liquid consists of a pure chemical in its liquid state. Examples include mineral oil, isoflurane, and ether. This dosage form term is not applied to solutions.

(See Emulsions.)

Lozenges are solid oral dosage forms that are designed to dissolve or disintegrate slowly in the mouth. They contain one or more drug substances that are slowly liberated from the, typically, flavored and sweetened base. They are frequently intended to provide local action in the oral cavity or the throat but also include those intended for systemic absorption after dissolution. The typical therapeutic categories of drug substances delivered in lozenges are antiseptics, analgesics, decongestants, antitussives, and antibiotics. Molded lozenges are called cough drops or pastilles but these terms are not used in naming pharmacopeial articles. Lozenges prepared by compression or by stamping or cutting from a uniform bed of paste are sometimes known as troches (a term not used in naming pharmacopeial articles). Compressed or stamped lozenges are often produced in a circular shape.

Lozenges can be made using sugars such as sucrose and dextrose, or can provide the benefits of a sugar-free formulation that is usually based on sorbitol or mannitol. Polyethylene glycols and hypromellose are sometimes included to slow the rate of dissolution.

Ointments are semisolid preparations generally intended for external application to the skin or mucous membranes. Drug substances delivered in ointments are intended for local action or for systemic absorption. Ointments usually contain less than 20% water and volatiles, and more than 50% hydrocarbons, waxes, or polyols as the vehicle. Ointment bases recognized for use as vehicles fall into four general classes: hydrocarbon bases, absorption bases, water-removable bases, and water-soluble bases.

The choice of an ointment base depends on the action desired, the characteristics of the incorporated drug substance, and the latter's bioavailability if systemic action is desired. The product's stability may require the use of a base that is less than ideal in meeting other quality attributes. Drug substances that hydrolyze rapidly, for example, are more stable in hydrocarbon bases than in bases that contain water.

Pastes are semisolid preparations of stiff consistency and contain a high percentage (20%–50%) of finely dispersed solids. Pastes are intended for application to the skin, oral cavity, or mucous membranes. Pastes ordinarily do not flow at body temperature and thus can serve as occlusive, protective coatings. As a consequence, pastes are more often used for protective action than are ointments.

Fatty pastes that have a high proportion of hydrophilic solids appear less greasy and are more absorptive than ointments. They are used to absorb serous secretions and are often preferred for acute lesions that have a tendency toward crusting, vesiculation, or oozing.

Dental pastes are applied to the teeth. Other orally administered pastes may be indicated for adhesion to the mucous membrane for a local effect.

In veterinary medicine, pastes are typically administered orally and are intended for systemic delivery of drug substances. The paste is squeezed into the mouth of the animal, generally at the back of the tongue, or is spread inside the mouth.

Pellets are dosage forms composed of small, solid particles of uniform shape sometimes called beads, although the use of the term “beads” as a dosage form is not preferred. Typically, pellets are nearly spherical but this is not required. Pellets may be administered by the oral (gastrointestinal) or by the injection route (see also Implants). Pellet formulations may provide several advantages, including physical separation for chemically or physically incompatible materials, extended release of the drug substance, or delayed release to protect an acid-labile drug substance from degradation in the stomach or to protect stomach tissues from irritation. Extended-release pellet formulations may be designed with the drug substance dispersed in a matrix, or the pellet may be coated with an appropriate polymer coating that modifies the drug-release characteristics. Alternatively, the pellet design may combine these two approaches. In the case of delayed-release formulations, the coating polymer is chosen to resist dissolution at the lower pH of the gastric environment but to dissolve in the higher pH intestinal environment. Injected or surgically administered pellet preparations (see Implants) are often used to provide continuous therapy for periods of months or years.

Pellet dosage forms may be designed as single or multiple entities. Often, implanted pellets will contain the desired drug substance content in one or several units. Oral pellets are typically contained within hard gelatin capsules for administration. Although there are no absolute requirements for size, the useful size range of pellets is governed by the practical constraints of the volume of commonly used capsules and the need to include sufficient numbers of pellets in each dose to ensure uniform dosing of the drug substance. As a result, many pellets used for oral administration fall within a size range of 710 µm to 2.5 mm. Pellet formulations are sometimes used to minimize variability associated with gastric retention of larger dosage forms.

Delayed-release pellet formulations and some extended-release formulations are prepared by applying a coating to the formulated particles. The coating must be applied as a continuous film over the entire surface of each particle. Because a small population of imperfectly coated particles may be unavoidable, oral pellets are designed to require the administration of a large number in a single dose to minimize any adverse influence of imperfectly coated pellets on drug delivery.

Pills are drug substance-containing small, spherical, solid bodies intended for oral administration. The pill dosage form has been largely replaced by compressed tablets and by capsules. Unlike tablets, pills are usually prepared by a wet massing, piping, and molding technique. This term is frequently incorrectly used as a general term to describe solid oral dosage forms, such as tablets and capsules.

A plaster is a semisolid substance for external application that is supplied on a support material. Plasters are applied for prolonged periods to provide protection, support, or occlusion (maceration). This term is not preferred and should not be used for new drug product titles. Plasters consist of an adhesive layer that may contain active substances. This layer is spread uniformly on an appropriate support that is usually made of a rubber base or synthetic resin. Unmedicated plasters are designed to provide protection or mechanical support to the site of application. Plasters are available in a range of sizes or cut to size to effectively provide prolonged contact to the site of application. They adhere firmly to the skin but can be peeled off the skin without causing injury.

Powders are defined as a single solid or a mixture of solids in a finely divided state. Powders used as pharmaceutical dosage forms may contain one or more drug substances and can be used as is or can be mixed with a suitable vehicle for administration. Powders are grouped according to the following terms: very coarse, coarse, moderately coarse, fine, and very fine (see Powder Fineness 811). Powders can be intended for internal or external use. Powders for external use are typically dusted onto the skin or applied to bandages or clothing. Powders for internal use can be applied to accessible mucous membranes with suitable applicators or are entrained in air streams for application to the nose or lungs.

The performance of powder dosage forms can be affected by the physical characteristics of the powder. For example, particle size can influence the dissolution rate of the particles and thus the bioavailability and/or effectiveness at the site of action. Externally applied powders should have a particle size of 150 µm or less (typically in the 50- to 100-µm range to prevent a gritty feel on the skin that could further irritate traumatized skin). The particle size of powders delivered to the lung or nose influences where the powder is deposited. Particle size can influence the mixing, segregation, and aggregation of the particles, which can affect the delivery and unformity of the dosage form.

In veterinary medicine, a powder that needs to be reconstituted prior to administration has been called a concentrate (e.g., drug products administered via drinking water). Such use of the term “concentrate” is no longer preferred.

Soaps and shampoos are solid or liquid preparations intended for topical application to the skin or scalp followed by subsequent rinsing with water. Soaps and shampoos are emulsions, suspensions, or surface-active compositions that readily form emulsions, micelles, or foams upon the addition of water followed by rubbing. Incorporation of drug substances in soaps and shampoos combines the cleansing/degreasing abilities of the vehicle and facilitates the topical application of the drug substance to affected areas, even large areas, of the body. The surface-active properties of the vehicle facilitate contact of the drug substance with the skin or scalp. Medicated soap and shampoo formulations frequently contain suitable antimicrobial agents to protect against bacteria, yeast, and mold contamination.

A solution is a preparation that contains one or more dissolved chemical substances in a suitable solvent or mixture of mutually miscible solvents. Because molecules of a drug substance in solution are uniformly dispersed, the use of solutions as dosage forms generally provides assurance of uniform dosage upon administration and good accuracy when the solution is diluted or otherwise mixed.

Substances in solutions are more susceptible to chemical instability than they are in the solid state and, dose-for-dose, are generally heavier and more bulky than solid dosage forms. These factors increase the cost of packaging and shipping relative to that of solid dosage forms. Solution dosage forms can be administered by injection, inhalation, and the mucosal, topical/dermal, and gastrointestinal routes. A solution administered by injection is officially titled “injection” (see 1).

Some solutions are designed to form a mass in situ. These solutions comprise polymer, drug substance, and solvent for the polymer. The polymer solvent can be water or an organic solvent. After administration of the solution to a patient by subcutaneous or intramuscular administration, it forms a gel or a solid polymeric matrix that traps the drug substance and extends the drug substance release for days or months.

Solutions intended for oral administration usually contain flavorings and colorants to make the medication more attractive and palatable for the patient or consumer. When needed, they also may contain stabilizers to maintain chemical and physical stability and preservatives to prevent microbial growth.

Solutions are sometimes placed on devices such as swabs, cloths, or sponges, that aid application.

In veterinary medicine, a solution that needs to be diluted prior to administration has been called a concentrate (e.g., drug products administered via drinking water). Such use of the term “concentrate” is no longer preferred.

Spray preparations may deliver either accurately metered or nonmetered amounts of formulation.

A spray drug product is a dosage form that contains a drug substance in the liquid state as a solution or suspension and is intended for administration as a mist. Sprays are distinguished from aerosols in that spray containers are not pressurized. Most of the sprays are generated by manually squeezing a flexible container or actuation of a pump that generates the mist by discharging the contents through a nozzle.

Depending on the design of the formulation and the valve system, the droplets generated may be intended for immediate inhalation through the mouth and deposition in the pulmonary tree, or for inhalation into the nose and deposition in the nasal cavity.

The mechanism for droplet generation and the intended use of the preparation distinguish various classes of sprays. A spray may be composed of a pump, container, actuator, valve, nozzle, or mouthpiece in addition to the formulation containing the drug(s), solvent(s), and any excipient(s). The design of each component plays a role for the appropriate performance of the drug product and in determining the critical characteristics of the droplet size distribution. Droplet and particle size distributions, delivered dose uniformity, plume geometry, and droplet velocity are critical parameters that influence the efficiency of drug delivery. When the preparation is supplied as a multidose container, the addition of a suitable antimicrobial preservative may be necessary. Spray formulations intended for local or systemic effect typically have an aqueous base and may contain excipients to control pH and viscosity. In addition, depending on the route of administration, the formulation may be isotonic. For additional information, see 5 and 601.

A strip is a dosage form or device in the shape of a long, narrow, thin, absorbant, solid material such as filter paper. Typically it is sterile and it may be impregnated with a compound or be gauged to allow measurements for diagnostic purposes, such as in measuring tear production. The term “strip” should not be used when another term such as “film” is more appropriate.

Suppositories are dosage forms adapted for application into the rectum. They melt, soften, or dissolve at body temperature. A suppository may have a local protectant or palliative effect, or may deliver a drug substance for systemic or local action.

Suppository bases typically include cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, mixtures of polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. The suppository base can have a notable influence on the release of the drug substance(s). Although cocoa butter melts quickly at body temperature, it is immiscible with body fluids and this inhibits the diffusion of fat-soluble drug substances to the affected sites. Polyethylene glycol is a suitable base for some antiseptics. In cases when systemic action is desired, incorporating the ionized rather than the nonionized form of the drug substance may help maximize bioavailability. Although nonionized drug substances partition more readily out of water-miscible bases such as glycerinated gelatin and polyethylene glycol, the bases themselves tend to dissolve very slowly, which slows drug substance release. Cocoa butter and its substitutes (e.g., Hard Fat) perform better than other bases for allaying irritation in preparations intended for treating internal hemorrhoids. Suppositories for adults are tapered at one or both ends and usually weigh about 2 g each.

A suspension is a biphasic preparation consisting of solid particles dispersed throughout a liquid phase. Suspension dosage forms may be formulated for specific routes of administration such as oral, topical, inhalation, ophthalmic, otic, and injection. Some suspensions are prepared and ready for use, and others are prepared as solid mixtures intended for reconstitution with an appropriate vehicle just before use.

Inhalation suspensions (see 5), ophthalmic suspensions, injectable suspensions, and some otic suspensions are prepared in sterile form. Suspensions are generally not injected intravenously, epidurally, or intrathecally unless the product labeling clearly specifies these routes of administration.

Some liposomal drug products are referred to as suspensions because they can settle and require resuspension prior to administration (see 1).

Some suspensions are designed to form a mass in situ. These suspensions comprise polymer, drug substance, and solvent for the polymer. The polymer solvent can be water or an organic solvent. After administration of the suspension to a patient by subcutaneous or intramuscular administration, it forms a gel or a solid polymeric matrix that traps the drug substance and extends the drug substance release for days or months.

Historically, the term “milk” was sometimes used for suspensions in aqueous vehicles intended for oral administration (e.g., Milk of Magnesia). The term “magma” is often used to describe suspensions of inorganic solids, such as clays in water, that display a tendency toward strong hydration and aggregation of the solid, giving rise to gel-like consistency and thixotropic rheological behavior (e.g., Bentonite Magma). In the past, the term “lotion” referred to both topical suspensions and topical emulsions. Now the term only refers to topical emulsions (see Emulsions).

Limited aqueous solubility of the drug substance(s) is the most common rationale for developing a suspension. Other potential advantages of an oral suspension include taste masking and improved patient compliance because of the more convenient dosage form. When compared to solutions, suspensions can have improved chemical stability. Ideally, a suspension should contain small uniform particles that are readily suspended and easily redispersed following settling. Unless the dispersed solid is colloidal, the particulate matter in a suspension will likely settle to the bottom of the container upon standing. Such sedimentation may lead to caking and solidification of the sediment and difficulty in redispersing the suspension upon agitation. To prevent such problems, manufacturers commonly add ingredients to increase viscosity and the gel state of the suspension or flocculation, including clays, surfactants, polyols, polymers, or sugars. Frequently, thixotropic vehicles are used to counter particle-settling tendencies, but these vehicles must not interfere with pouring or redispersal. Additionally, the density of the dispersed phase and continuous phase may be modified to further control settling rate. For topical suspensions, rapid drying upon application is desirable.

Temperature can influence the viscosity (and thus suspension properties and the ease of removing the dose from the bottle), and temperature cycling can lead to changes in the particle size of the dispersed phase via Ostwald ripening. When manufacturers conduct stability studies to establish product shelf life and storage conditions, they should cycle conditions (freeze/thaw) to investigate temperature effects.

Unless studies confirm that the formulation will not support microbial growth, suspension preparations packaged to provide multiple doses should contain suitable antimicrobial agents to protect against bacterial, yeast, and mold contamination (see 51) or other appropriate measures should be taken to avoid microbial contamination.

Suspensions for reconstitution are dry powder or granular mixtures that require the addition of water or a supplied formulated diluent before administration. This formulation approach is frequently used when the chemical or physical stability of the drug substance or suspension does not allow sufficient shelf life for a preformulated suspension. Typically, these suspensions are refrigerated after reconstitution to increase their shelf life. For this type of suspension, the powder blend is uniform and the powder readily disperses when reconstituted.

Injectable suspensions are generally intended for either subcutaneous or intramuscular routes of administration and should have a controlled particle size, typically in the range of 5 µm or smaller. The rationale for the development of injectable suspensions may include poor drug substance solubility, improved chemical stability, prolonged duration of action, and avoidance of first-pass metabolism. Care is needed in selecting the sterilization technique because it may affect product stability or alter the physical properties of the material.

In veterinary medicine, a suspension that needs to be diluted prior to administration has been called a concentrate (e.g., drug products administered via drinking water). Such use of the term “concentrate” is no longer preferred.

Tablets are solid dosage forms in which the drug substance is generally blended with excipients and compressed into the final dosage. Tablets are the most widely used dosage form in the United States. Tablet presses use steel punches and dies to prepare compacted tablets by the application of high pressures to powder blends or granulations. Tablets can be produced in a wide variety of sizes, shapes, and surface markings. Capsule-shaped tablets are commonly referred to as caplets, although the term is not preferred as a dosage form name. Specialized tablet presses may be used to produce tablets with multiple layers or with specially formulated core tablets placed in the interior of the final dosage form. These specialized tablet presentations can delay or extend the release of the drug substance(s) or physically separate incompatible drug substances. Tablets may be coated by a variety of techniques to provide taste masking, protection of photo-labile drug substance(s), extended or delayed release, or unique appearance (colors). When no deliberate effort has been made to modify the drug substance release rate, tablets are referred to as immediate-release.

A tape is a dosage form suitable for delivering drug substances to the skin. It consists of a drug substance(s) impregnated into a durable yet flexible woven fabric or extruded synthetic material that is coated with an adhesive agent. Typically the impregnated drug substance is present in the dry state. The adhesive layer is designed to hold the tape securely in place without the aid of additional bandaging. Unlike transdermal systems, tapes are not designed to control the release rate of the drug substance. The term “tape” is not preferred and should not be used for new drug product titles.

The drug substance content of tapes is expressed as amount per surface area with respect to the tape surface exposed to the skin. The use of an occlusive dressing with the tape enhances the rate and extent of delivery of the drug substance to deeper layers of the skin and may result in greater systemic absorption of the drug substance.

As an attribute, spray describes the generation of droplets of a liquid or solution to facilitate application to the intended area.