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Drug Dosage Forms II (PHR 312)

SOLID DOSAGE FORMSSOLID DOSAGE FORMS

Powders Granules

Tablets Capsules

Suppositories

Course coordinator: Ph. D. TuxxÜ ^tááxÅTuxxÜ ^tááxÅTuxxÜ ^tááxÅTuxxÜ ^tááxÅ, Department of Pharmaceutics

Course objectives:

After completion of the course, the student will be able to define, classify and discuss the different types, uses and methods of preparation, packaging, storage and evaluation of solid dosage forms; including powders, granules, tablets, capsules and suppositories.

Recommended text books:

- Ansel's Pharmaceutical Dosage Forms & Drug Delivery Systems, Eighth Edition, L.V.Allen, Jr. N.G. Popovich and H.C. Ansel (Eds), Lippincott Williams & Wilkins 2005. - Pharmaceutics: The Science of Dosage Form Design. By Michael Aulton. - Remington, the science and practice of pharmacy,21st Edition, Lippincott Williams and Wilkins.

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Drug Dosage Forms II (PHR 312)

Lecture 1

SOLID DOSAGE FORMS

Solid dosage forms include; powders, granules, tablets,

capsules and suppositories (suppositories may be also classified as semi-solid dosage form) Advantages of solid dosage forms

1. More stable than liquids, with longer expiration dates. 2. Easy shipping and handling. 3. Less needed shelf space. 4. No preservation requirements. 5. Accurate dosage (single dose). 6. Suitable for sustained release preparation.

Disadvantages of solid dosage forms Their preparation needs complicated and expensive machines.

Powders and granules as a dosage form

Pharmaceutical powder is a mixture of finely divided drugs and/or chemicals in a dry form that may be intended for internal (oral powders) or external (topical or dusting powder) use.

Powders

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Granules are prepared aggregates of powdered materials to form a larger particle (2-4 mm). Granules may be used as such (granules of medicinal value) or in making tablets and capsules (because of better flowability of granules compared to powders). (Very fine particles do not flow as freely as large particles).

The flowability of powders and granules is measured by the angle of repose.

Granules

Pharmaceutical powder is a mixture of finely divided drugs and/or chemicals in a dry form that may be intended for internal (oral powders) or external (topical or dusting powder) use. Powders may be provided to the patient in bulk or divided.

1- Bulk powder: - Bulk powder is limited to non-potent drugs. - The powder mixture is packed into a suitable bulk

container to facilitate dosing, such as; A wide mouth glass jar

A perforated or sifter can for external (dusting) powder, e.g. Talc powder. An aerosol container for topical application.

Examples for powders commonly dispensed in a bulk form 1- Powders used in a dry form 2- Powders to be dissolved in water before use 3- Powders for reconstitution

PHARMACEUTICAL POWDERS

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1111---- Powders used in a dry formPowders used in a dry formPowders used in a dry formPowders used in a dry form

A- Powders for topical application e.g. antibacterial and antifungal powders, or non-medicated powders e.g. Talc powder (protective action).

B- Dental cleansing powders C- Insufflations: They are medicated powders to be

applied into body cavity, e.g. ear, nose, throat or vagina, by means of a device known as "insufflator" or a powder blower.

General purpose insufflator

2222---- Powders to be dissolved in water before usePowders to be dissolved in water before usePowders to be dissolved in water before usePowders to be dissolved in water before use A- Antacids and laxatives (large dose) are used by mixing

the directed amount of powder (usually one teaspoonful) in a portion of water before swallowing.

B- Dietary/Food supplements =>?اABCت اEFGFCا C- Douche powders (e.g. vaginal douche) are dissolved in

warm water before application.

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Bulk powderBulk powderBulk powderBulk powderssss in the marketin the marketin the marketin the market

Talc powderTalc powderTalc powderTalc powder (Perforated can)(Perforated can)(Perforated can)(Perforated can)

PPPPowder aerosolowder aerosolowder aerosolowder aerosol Laxative powder Laxative powder Laxative powder Laxative powder

Nutritional Nutritional Nutritional Nutritional supplementsupplementsupplementsupplement Dental powderDental powderDental powderDental powder

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3333---- Powders for reconstitutionPowders for reconstitutionPowders for reconstitutionPowders for reconstitution (important)(important)(important)(important) A- Oral antibiotic; for stability problems the antibiotic is prepared in a dry form (powder or granules) and packed in a sealed bottle, a given amount of water is added before use. Once it is reconstituted the patient should be warned of the short shelf life (usually 1-2 weeks).

B- Powders for injection; They may be classified as bulk or divided powders. Injections of drugs that are unstable in solution must be made immediately prior to use and are presented as sterile powders in ampoules. Sterile water for injection is added from a second ampoule and the injection is used immediately.

Vials fo r reconstitu tion

Drug powder

Sterile vehicle

After recostitution

Fill the bottle with purified water till this mark, before use

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2- Divided powder

Divided powders are similar formulations to bulk powders but individual doses are separately wrapped. Traditionally in papers (unsatisfactory for most products, specially if the ingredients are hygroscopic, volatile or deliquescent). Modern packaging materials of foil and plastic laminates have placed paper wrapping (WHY?) because they offer superior protective qualities and are amenable to use on high speed packaging machines.

Granules are prepared aggregates of powdered materials to form a larger particle (2-4 mm). Granules may be used as such (granules of medicinal value) or in making tablets and capsules.

Advantages of granules over powders: 1- Granules are more flowable compared to powders. 2- Segregation of the constituents of the powder mixture

could be avoided by granulation. {Segregation occurs due to difference in particle size or densities (small particles and denser particles concentrated in the base of the container and vice versa), by granulation same particles i.e. narrow range of p.s. distribution, so that no segregation}.

Segregation in powders

3- Granules are more stable against humidity and

atmosphere and less likely to make cake or harden upon standing. (due to less exposed surface area compared to powders).

Granules

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4- Granules are more easily wetted by liquids than light and fluffy powders (which tend to float on the surface) and are more preferable for dry products intended to be constituted into solution or suspension (mostly antibiotics for stability reasons).

EFFERVESCENT GRANULES They are granules of drug in a dry mixture usually composed of Sodium bicarbonate, Citric acid and Tartaric acid, when added to water, the acids and the base react to liberate CO2, resulting in effervescence.

WHY a combination of Tartaric acid and Citric acid is used as an effervescent base rather than either acid alone? Because when tartaric acid is used alone, chalky friable granules are produced, and Citric acid alone results in sticky mixture to difficult to granulate.

Advantages of effervescent granules: 1. Attractive dosage form for the public. 2. The carbonated solution masks undesirable taste of

the drug. 3. The liberated CO2 gas is used as a therapeutic

agent; it increases gastric secretions and hence facilitates digestion, and it acts as antinauseant.

4. Using granules rather than powders decreases the rate of solution and prevents uncontrollable effervescence.

It is important to protect effervescent granules from moisture during manufacture and storage to prevent premature reaction between acids and base.

Disadvantages of effervescent granules: 1. Instability in presence of moisture. 2. Problems in packaging and storage.

Methods of preparation of effervescent granules: 1. Fusion method 2. Wet method

Effer Granules "Divided"

Effer Granules "Bulk"

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TABLETSTABLETSTABLETSTABLETS

Tablets are solid preparations each

containing a single dose of one or more active ingredients

and usually obtained by compressing uniform volume of

particles, some are prepared by molding.

Tablet compression machine Tablet mold

(Large-scale production) (Small-scale)

They are usually prepared by the aid of some

pharmaceutical excipients (additives) to:

- help in tableting procedure.

- ensure that the drug will be released as intended. The term ''tablet'' (from the Latin tabuletta) is associated with the appearance of the dosage form i.e. tablets are small disc-like or cylindrical specimens).

{ N.B. In European Pharmacopoeia, tablets are called "compressi" which reflect the method of preparation.}

Most tablets are used for oral administration of drugs, others are administered sublingually, buccaly or vaginally.

Advantages of tablets (Tablets are popularWHY?): In U.K. Tablets represents about 46% of all other dosageforms. 1- Compared to liquid dosage formschemical and physical stability2- Packaging in blister packs can also enhance the stability of tablets.3- They provide an content variability4- Low manufacturing cost.5- Easy to package and ship.6- Simple to identify. (or stamped to aid tablet recognition7- Manufacturing processes and techniques can provide tablets special properties

example enteric coatingsformulations.

Disadvantages of tablets as a dosage form:1- Poor bioavailability of poorly soluble drugs or poorly

absorbable drugs.2- Some drugs may cause local irritation effect harm

GI mucosa. 3- Some drugs resist compression into tablet.4- Difficulty in swallowing in some patients; pediatrics and

geriatrics. 5- In emergency cases, intravenous or intramuscular

injections are more effective.

Classification of tablets I- According to drug release rate from the taclassification): a- Immediate release (Conventional) tablet. b- Modified release tablet (Extended and Delayed release tablet). II- According to method of manufacturing:

a- Compressed tablet.b- Molded tablet.

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Advantages of tablets (Tablets are popular

In U.K. Tablets represents about 46% of all other dosage

liquid dosage forms, tablets possess chemical and physical stability

Packaging in blister packs can also enhance the stability of tablets.

They provide an accurately measured dose and content variability of the unit dose.

Low manufacturing cost. Easy to package and ship. Simple to identify. (Coatings can be colored

to aid tablet recognition) Manufacturing processes and techniques

provide tablets special properties; for

enteric coatings or sustained release

Disadvantages of tablets as a dosage form:Poor bioavailability of poorly soluble drugs or poorly absorbable drugs. Some drugs may cause local irritation effect harm

resist compression into tablet. Difficulty in swallowing in some patients; pediatrics and

In emergency cases, intravenous or intramuscular more effective.

Classification of tablets

According to drug release rate from the tablet (USP

Immediate release (Conventional) tablet. Modified release tablet (Extended and Delayed release

According to method of manufacturing: Compressed tablet. Molded tablet.

Advantages of tablets (Tablets are popular.

In U.K. Tablets represents about 46% of all other dosage

, tablets possess more

Packaging in blister packs can also enhance the

and low

Disadvantages of tablets as a dosage form: Poor bioavailability of poorly soluble drugs or poorly

Some drugs may cause local irritation effect harm

Difficulty in swallowing in some patients; pediatrics and

In emergency cases, intravenous or intramuscular

blet (USP

Modified release tablet (Extended and Delayed release

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I- According to drug release rate from the tablet (USP classification): a- Immediate release (Conventional) tablet: The tablet is intended to be released rapidly after administration, or the tablet is dissolved and administered as solution. It is the most common type and includes: - Disintegrating tablet - Chewable tablet - Sublingual tablet - Buccal tablet - Effervescent tablet

b- Modified-release tablet: They have release features based on; time, course or location. They must be swallowed intact.

Modified-release tablet

1-Extended-release tablet 2- Delayed-release tablet

Drug release is delayed due to physiological conditions e.g. pH (a lag period followed by normal release). The best example is enteric coated tablets; the drug is released in the upper part of the small intestine after which the preparation has passed the stomach. If the drug is sensitive to acid, or is irritant to the stomach lining, an enteric coating can be used.

Allowing the reduction in dosing frequency.

Cumulative amount of drug released

Immediate-

release tablet

Delayed-

release tablet

Extended-

release tablet

Time

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II- According to method of manufacturing: a- Compressed tablet:

It is obtained by compressing uniform volume of particles using "Tablet compression machine". It's used for large scale production.

Tablet compression machine b- Molded tablet:

Molding means shaping and hardening of semi-solid mixture of drug and excipients. It is obtained using "tablet mold". It is restricted for small-dose tablet and small-scale production.

Tablet mold