USP 1151 GENERAL

CHAPTERS
 USP 1151 PHARMACEUTICAL DOSAGE FORMS

GENERAL CONSIDERATIONS: This chapter provides general descriptions of and

definitions for drug products, or dosage forms, commonly used to administer the drug
substance (active pharmaceutical ingredient; API). It discusses general principles involved in
the manufacture or compounding of these dosage forms
A dosage form is a pharmaceutical preparation consisting of drug substance(s) and/or
excipient(s) to facilitate dosing, administration, and delivery of the content of the drug
product or placebo to the patient. The design, materials, manufacturing, and testing of all
dosage forms target drug product quality. A testing protocol must consider not only the
physical, chemical, microbiological, and biological properties of the dosage form as
appropriate, but also the administration route and desired dosing regimen.
Tests to ensure compliance with USP standards for dosage form performance fall into one
of the following areas.
Dose Uniformity Consistency in dosing for a patient or consumer requires that the variation
in the drug substance content of each dosage unit be accurately controlled throughout the
manufactured batch or compounded lot of drug product. Uniformity of dosage units typically
is demonstrated by one of two procedures: content uniformity or weight variation. The
procedure for content uniformity requires the appropriate assay of the drug substance content
of individual units. The procedure for weight variation uses the weight of the individual units
to estimate their content. Weight variation may be used where the underlying distribution of
the drug substance in the blend is presumed to be uniform and well-controlled, as in
solutions. In such cases, the content of the drug substance may be adequately estimated by
the net weight. Content uniformity does not rely on the assumption of blend uniformity and
can be applied in all cases. Successful development and manufacture of dosage forms
requires careful evaluation of the drug substance particle or droplet size, incorporation
techniques, and excipient properties.
Stability Drug product stability involves the evaluation of chemical stability, physical
stability, and performance over time. The chemical stability of the drug substance in the
dosage form matrix must support the expiration dating for the commercially prepared dosage
forms and a beyond-use date for a compounded dosage form.
Test procedures for potency must be stability indicating Degradation products should be
quantified. In the case of dispersed or emulsified systems, consideration must be given to
the potential for settling or separation of the formulation components. Any physical
changes to the dosage form must be easily reversed (e.g., by shaking) prior to dosing or
administration. For tablets, capsules, oral suspensions, and implants, in vitro release test
procedures such as dissolution and disintegration provide a measure of continuing
consistency in performance over time
Bioavailability Bioavailability is influenced by factors such as the method of manufacture or
compounding, particle size, crystal form (polymorph) of the drug substance, the properties of
the excipients used to formulate the dosage form, and physical changes as the drug product
ages. Assurance of consistency in bioavailability over time (bioequivalence) requires close
attention to all aspects of the production (or compounding) and testing of the dosage form.

1
With proper justification, in vitro release testing (e.g., disintegration and dissolution) may be
used as a surrogate to demonstrate consistent availability of the drug substance from the
formulated dosage.

Release Profile Two principal categories of drug release are recognized: immediate-release
and modified-release.
“Immediate-release” is observed when no deliberate effort has been made to modify
the drug substance release profile. For example, capsules and tablets are considered
immediate-release even if a disintegrating agent or a lubricant has been used.
“Modified-release” is a term used when the rate and/or time of release of the drug
substance is altered as compared to what would be observed or anticipated for an
immediate-release product. Two modified-release profiles, delayed-release and
extended-release, are recognized.
“Delayed-release” is used when deliberate formulation achieves a delay in the release
of the drug substance for some period of time after initial administration. For oral
products, expressions such as “enteric-coated” or “gastro-resistant” also have been
used where release of the drug substance is prevented in the gastric environment but
promoted in the intestinal environment. However, the term “delayed-release” is used
for official article titles.
“Extended-release” is used when the deliberate formulation achieves prolongation of
drug substance release compared to that observed or anticipated for an immediate-
release dosage form. Expressions such as “prolonged-release”, “repeat-action”,
“controlled-release”, “long-acting”, and “sustained-release” also have been used to
describe such dosage forms. However, the term “extended-release” is used for official
article titles
Route of administration the primary routes of administration for pharmaceutical dosage
forms can be defined as parenteral, gastrointestinal, topical, mucosal, and inhalation. Each
has subcategories as needed. Many tests used to ensure quality generally are applied across
all of the administration routes, but some tests are specific for individual routes.
For example, products intended for injection must be evaluated using Sterility Tests
Bacterial Endotoxins Test, or Pyrogen Test, and the manufacturing process (and
sterilization technique) employed for parenteral (by injection) should ensure
compliance with these tests. Tests for particulate matter may be required for certain
dosage forms depending on the route of administration (e.g., by injection—Particulate
Matter in Injections mucosal—Particulate Matter in Ophthalmic Solutions or
inhalation.
Additionally, dosage forms intended for the inhalation route of administration must be
monitored for particle size and spray pattern (for a metered-dose inhaler or dry
powder inhaler) and droplet size (for nasal sprays)
Packaging and Storage Suitable packaging is determined for each product. For additional
information about meeting packaging requirements listed in the individual labelling, refer to
Packaging and Storage Requirements 659, Containers—Performance Testing 671, and Good
Repackaging Practices 1178. Product labelling must specify storage requirements that
describe environmental conditions, limitations, and restrictions. For instance, exposure to

2
excessive temperature, humidity, and light can influence the ability of the packaging to
protect the product.
Labelling Statements Some dosage forms or articles have mandatory labelling statements
that are given in the Code of Federal Regulations (e.g., 21 CFR 201.320 and 21 CFR 369.21).
The text of 21 CFR should be consulted to determine the current recommendations.

PRODUCT QUALITY TESTS, GENERAL International Council for Harmonisation

(ICH) Guidance Q6A recommends specifications (list of tests, references to analytical
procedures, and acceptance criteria) to ensure that drug products are safe and effective at the
time of release and over their shelf life. Tests that are universally applied to ensure safety,
efficacy, strength, quality, and purity include description, identification, assay, and
impurities.
Description The Definition section in a USP monograph describes the drug product and
specifies the range of acceptable assayed content of the drug substances present in the dosage
form. For certain products, the Definition includes any relevant additional information, such
as the presence or absence of other components, excipients, or adjuvants, and cautionary
statements on toxicity and stability. While appearance information to aid in identification is
used in a regulatory submission (e.g., a qualitative description of size, shape, colour, etc.) it is
typically not required as part of a USP monograph. This information is drug product specific
Identification Identification tests should establish the identity of the drug substance(s)
present in the drug product and should discriminate between compounds of closely related
structure that are likely to be present. Identification tests should be specific for the drug
substance(s). For example, the infrared absorption spectrum is often used
If no suitable infrared spectrum can be obtained, other analytical methods can be
used. Near-infrared (NIR) or Raman spectrophotometric methods also could be
acceptable as the sole identification method of the drug product formulation.
Identification by a chromatographic retention time from a single procedure is not
regarded as specific. The use of retention times from two chromatographic procedures
for which the separation is based on different principles or a combination of tests in a
single procedure can be acceptable
Assay A specific and stability-indicating test should be used to determine the strength (drug
substance content) of the drug product. Some examples of these procedures are Antibiotics—
Microbial Assays, or Assay for Steroids. In cases when the use of a nonspecific assay is
justified (e.g., Titrimetric), other supporting analytical procedures should be used to achieve
specificity. When evidence of excipient interference with a nonspecific assay exists, a
procedure with demonstrated specificity should be used.
Impurities Process impurities, synthetic by products, and other inorganic and organic
impurities may be present in the drug substance and excipients used in the manufacture of the
drug product. These impurities are evaluated by tests in the drug substance and excipients
monographs. Impurities arising from degradation of the drug substance or from the drug-
product manufacturing process should be monitored.
Physicochemical Properties Examples include pH (791), Viscosity—Capillary Methods
(911) or Viscosity—Rotational Methods (912), and Specific Gravity (841)

3
Particle Size For some dosage forms, particle size can have a significant effect on dissolution
rates, bioavailability, therapeutic outcome, and stability. Procedures such as those found in
Inhalation and Nasal Drug Products: Aerosols, Sprays, and Powders—Performance Quality
Tests (601) and Particle Size Distribution Estimation by Analytical Sieving (786) could be
used.
Microbial Limits The type of microbial tests and acceptance criteria are based on the nature
of the nonsterile drug product, method of manufacture, and the route of administration see
Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests (61),
Microbiological Examination of Nonsterile Products: Tests for Specified Microorganisms
(62), and Microbiological Examination of Nonsterile Products: Acceptance Criteria for
Pharmaceutical Preparations and Substances for Pharmaceutical Use (1111).
Antimicrobial Preservative Content Acceptance criteria for preservative content in
multidose products should be established. They are based on the levels of antimicrobial
preservative necessary to maintain the product’s microbiological quality at all stages
throughout its proposed usage and shelf life
Antioxidant Content If antioxidants are present in the drug product, tests of their content
should be performed to maintain the product’s quality at all stages throughout its proposed
usage and shelf life.
Dissolution A test to measure the release of the drug substances from the drug product
normally is included for dosage forms such as tablets, capsules, suspensions, granules for
suspensions, implants, transdermal delivery systems (TDS), and medicated chewing gums.
Single-point measurements typically are used for immediate-release dosage forms. For
modified-release dosage forms, appropriate test conditions and sampling procedures are
established as needed. In some cases, dissolution testing may be replaced by disintegration
testing
Breaking Force and Friability These parameters are evaluated as in-process controls.
Acceptance criteria depend on packaging, supply chain, and intended use.
Leachables When evidence exists that leachables from the container–closure systems (e.g.,
rubber stopper, cap liner, or plastic bottle) have an impact on the safety or efficacy of the
drug product, a test is included to evaluate the presence of leachables.
Other Tests Depending on the type and composition of the dosage form, other tests such as
alcohol content, redispersibility, particle size distribution, rheological properties,
reconstitution time, endotoxins/pyrogens, particulate matter, functionality testing of delivery
systems, delivered dose uniformity, viscosity, and osmolarity may be necessary
DOSAGE FORMS
Capsules
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-

4
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 also may be made from cellulose
polymers (e.g., Hypromellose) 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.
TWO-PIECE OR HARD-SHELL CAPSULES Two-piece capsules consist of two
telescoping cap and body pieces in a range of standard sizes
ONE-PIECE OR SOFT-SHELL CAPSULES One-piece capsules typically are used to
deliver a drug substance as a solution or suspension. Liquid formulations placed into one-
piece capsules may offer advantages by comparison with dry-filled capsules and tablets in
achieving content uniformity of potent drug substance(s) or acceptable dissolution of drug
substance(s) with poor aqueous solubility. Because the contact between the shell wall and
its liquid contents is more intimate than in dry-filled capsules, undesired interactions may
be more likely to occur (including gelatin cross-linking and pellicle formation).
MODIFIED-RELEASE CAPSULES The release of drug substance(s) from capsules
can be modified in several ways. Two categories of modified-release capsule
formulations are recognized by USP.
Delayed-release capsules: Capsules are sometimes formulated to include enteric-coated
granules to protect acid-labile drug substances from the gastric environment or to prevent
adverse events such as irritation. Enteric-coated multiparticulate capsule dosage forms
may reduce variability in bioavailability associated with gastric emptying times for larger
particles (i.e., tablets) and may minimize the likelihood of a therapeutic failure when
coating defects occur during manufacturing. Alternatively, a coating may be applied to
the capsule shell to achieve delayed release of the contents.
Extended-release capsules: Extended-release capsules are formulated in such a manner
as to make the contained drug substance available over an extended period of time
following ingestion. Requirements for dissolution are typically specified in the individual
monograph. Methods for modifying drug substance release from capsules include coating
the filled capsule shells or the contents, in the case of dry-filled capsules.
PREPARATION
Two-piece capsules: Two-piece gelatin capsules are usually formed from blends of gelatins
that have relatively high gel strength in order to optimize shell clarity and toughness or from
Hypromellose. They may also contain colorants such as Drug & Cosmetic (D&C) and Food,
Drug, & Cosmetic (FD&C) dyes or various pigments, opaquing agents such as titanium
dioxide, dispersing agents, plasticizers, and preservatives.
Gelatin capsule shells normally contain between 12% and 16% water. The shells are
manufactured in one set of operations and later filled in a separate manufacturing process.
Two-piece shell capsules are made by a process that involves dipping shaped pins into gelatin
or Hypromellose solutions, followed by drying, cutting, and joining steps.
Powder formulations for two-piece gelatin capsules generally consist of the drug substance
and at least one excipient. Both the formulation and the method of filling can affect release of

5
the drug substance. In the filling operation, the body and cap of the shell are separated before
filling. Following the filling operation, the machinery rejoins the body and cap and ensures
satisfactory closure of the capsule by exerting appropriate force on the two pieces. The joined
capsules can be sealed after filling by a band at the joint of the body and cap or by a designed
locking joint between the cap and body. In compounding prescription practice, two-piece
capsules may be hand-filled. This permits the prescriber the choice of selecting either a single
drug substance or a combination of drug substances at the exact dose level considered best
for an individual patient.
One-piece capsules: One-piece capsules are formed, filled, and sealed in a single process on
the same machine and are available in a wide variety of sizes, shapes, and colours. The most
common type of one-piece capsule is that produced by a rotary die process that results in a
capsule with a seam. The soft gelatin shell is somewhat thicker than that of two-piece
capsules and is plasticized by the addition of polyols such as glycerin, sorbitol, or other
suitable materials. The ratio of the plasticizer to the gelatin can be varied to change the
flexibility of the shell depending on the nature of the fill material, its intended usage, or
environmental conditions. In most cases, one-piece capsules are filled with liquids. Typically,
drug substances are dissolved or suspended in a liquid vehicle. Classically, an oleaginous
vehicle such as a vegetable oil was used. However, nonaqueous, water-miscible liquid
vehicles such as the lower molecular weight polyethylene glycols are now more common.
The physicochemical properties of the vehicle can be chosen to ensure stability of the drug
substance as well as to influence the release profile from the capsule shell.
Tablets
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 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 used
in official article titles.
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 or
physically separate incompatible drug substances.
Tablets may be coated by a variety of techniques to provide taste masking, protection of
photo-labile drug substances, extended or delayed release, or unique appearance.
BUCCAL TABLETS Intended to be inserted in the buccal pouch, where the drug substance
is absorbed directly through the oral mucosa. Few drug substances are readily absorbed in
this way (examples are nitro-glycerine and certain steroid hormones).
CHEWABLE TABLETS Formulated and manufactured to produce a pleasant-tasting
residue in the mouth and to facilitate swallowing.
Hard chewable tablets are typically prepared by compaction, usually utilizing mannitol,
sorbitol, or sucrose as binders and fillers, and contain colours and flavours to enhance
their appearance and taste.

6
 Soft chewable tablets are typically made by a moulding or extrusion process, frequently
with more than 10% water to help maintain a pliable, soft product.
EFFERVESCENT TABLETS Prepared by compaction and contain, in addition to the
drug substances, mixtures of acids (e.g., citric acid or tartaric acid) and carbonates, and/or
sodium bicarbonate. Upon contact with water, these formulations release carbon dioxide,
producing the characteristic effervescent action.
HYPODERMIC TABLETS Moulded tablets made from completely and readily water-
soluble ingredients; formerly intended for use in making preparations for hypodermic
injection. They may be administered orally or sublingually when rapid drug substance
availability is required.
MODIFIED-RELEASE TABLETS Two categories of modified-release tablet
formulations are recognized by USP.
Delayed-release tablets: Tablets are sometimes formulated with acid-resistant or enteric
(also called “gastro-resistant”) coatings to protect acid-labile drug substances from the
gastric environment or to prevent adverse events such as irritation.
Extended-release tablets: Extended-release tablets are formulated in such a manner as to
make the drug substance available over an extended period of time following ingestion.
ORALLY DISINTEGRATING TABLETS Orally disintegrating tablets are intended
to disintegrate rapidly within the mouth to provide a dispersion before the patient
swallows the resulting slurry where the drug substance is intended for gastrointestinal
delivery and/or absorption. Some of these dosage forms have been formulated to facilitate
rapid disintegration and are manufactured by conventional means or by using
lyophilization or moulding processes.
SUBLINGUAL TABLETS Sublingual tablets are intended to be inserted beneath the
tongue, where the drug substance is absorbed directly through the oral mucosa. As with
buccal tablets, few drug substances are extensively absorbed in this way, and much of the
drug substance is swallowed and is available for gastrointestinal absorption.
TABLETS FOR ORAL SOLUTION Before administration, tablets for oral solution are
intended to be solubilized in a liquid diluent. In some cases, tablets for oral solution also
may be chewed or swallowed.
TABLETS FOR ORAL SUSPENSION Tablets for oral suspension are intended to be
dispersed in a liquid before administration as a suspension. The dosage form is tablets for
oral suspension when either the drug substance or the excipients do not dissolve when
dispersed in a liquid. In some cases, tablets for oral suspension also may be chewed or
swallowed.
TABLET TRITURATES Small, usually cylindrical, moulded or compacted tablets.
Tablet triturates traditionally were used as dispensing tablets in order to provide a
convenient, measured quantity of a potent drug substance for compounding purposes, but
they are rarely used today.
PREPARATION
Most compacted (compressed) tablets consist of the drug substances and a number of
excipients. These excipients may include fillers (diluents), binders, disintegrating
agents, lubricants, and glidants. Approved FD&C and D&C dyes or lakes, flavours,
and sweetening agents also may be present.

7
Fillers or diluents are added when the quantity of drug substances is too small or the
properties of the drug substance do not allow satisfactory compaction in the absence
of other ingredients.
Binders impart adhesiveness to the powder blend and promote tablet formation and
maintenance of drug substance uniformity in the tableting mixture.
Disintegrating agents facilitate reduction of the tablet into small particles upon contact
with water or biological fluids.
Lubricants reduce friction during the compaction and ejection cycles.
Glidants improve powder fluidity, powder handling properties, and tablet weight
control.
Colorants are often added to tablet formulations for aesthetic value or for product
identification.
Tablets are prepared from formulations that have been processed by one of three
general methods: wet granulation, dry granulation (roll compaction or slugging), or
direct compression.
Wet granulation: Involves the mixing of dry powders with a granulating liquid to
form a moist granular mass that is dried and sized prior to compression. It is
particularly useful in achieving uniform blends of low-dose drug substances and
facilitating the wetting and dissolution of poorly soluble, hydrophobic drug
substances.
Dry granulation: Can be produced by passing powders between rollers at elevated
pressure (roll compaction). Alternatively, dry granulation also can be carried out by
the compaction of powders at high pressures on tablet presses, a process also known
as slugging. In either case, the compacts are sized before compression. Dry
granulation improves the flow and handling properties of the powder formulation
without involving moisture in the processing.
Direct compression: Tablet processing involves dry blending of the drug substances
and excipients followed by compression. The simplest manufacturing technique,
direct compression, is acceptable only when the drug substance and excipients possess
acceptable flow and compression properties without prior process steps.
Tablets may be coated to protect the ingredients from air, moisture, or light; to mask
unpleasant tastes and odours; to improve tablet appearance; and to reduce dustiness.
In addition, coating may be used to protect the drug substance from acidic pH values
associated with gastric fluids or to control the rate of drug release in the
gastrointestinal tract.
The most common coating in use today is a thin film coating composed of a polymer
that is derived from cellulose. Sugar coating is an alternative, less common approach.
Sugar-coated tablets have considerably thicker coatings that are primarily sucrose
with a number of inorganic diluents.
A variety of film-coating polymers are available and enable the development of
specialized release profiles. These formulations are used to protect acid-labile drug
substances from the acidic stomach environment as well as to prolong the release of
the drug substance to reduce dosing frequency.

8
Injections Injections are not treated as a dosage form in this chapter. Chapter 1 provides
quality and other information about injectable products.
each container of an injection is filled with a volume in slight excess of the labelled “size” or
the volume that is to be withdrawn. The excess volumes recommended in Table 1 are usually
sufficient to permit withdrawal and administration of the labelled volumes.
Labelled Size (mL) Recommended Excess Volume
For Mobile Liquids (mL) For Viscous
Liquids (mL)
0.5 0.10 0.12
1.0 0.10 0.15
2.0 0.15 0.25
5.0 0.30 0.50
10 0.50 0.70
20 0.60 0.90
30 0.80 1.20
50 or more 2% 3