Drug Dosage Forms II (PHR 312)

SOLID DOSAGE FORMS

Powders

Granules

Tablets
Suppositories

Capsules

Course coordinator: Ph. D.

Tuxx ^tx, 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.

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

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 POWDERS
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

1- Powders 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

2- Powders 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 C- Douche powders (e.g. vaginal douche) are dissolved in warm water before application.

Bulk powders powders in the market

Talc powder
(Perforated can)

Powder aerosol

Laxative powder

Nutritional supplement

Dental powder

3- Powders for reconstitution (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).

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

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.

Sterile vehicle

Drug powder

After recostitution

V ials fo r re co n stitu tio n

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
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).

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 "Bulk"

Effer Granules "Divided"

TABLETS
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 (Large-scale production)

Tablet mold (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 popular. popular WHY?):

In U.K. Tablets represents about 46% of all other dosage forms. 1- Compared to liquid dosage forms, tablets possess more chemical and physical stability 2- Packaging in blister packs can also enhance the stability of tablets. 3- They provide an accurately measured dose and low content variability of the unit dose. 4- Low manufacturing cost. 5- Easy to package and ship. 6- Simple to identify. (Coatings ( can be colored or stamped to aid tablet recognition) recognition 7- Manufacturing processes and techniques can provide tablets special properties; for example enteric coatings or sustained release formulations.

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 tablet tablet (USP classification): 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.

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
Allowing the reduction in dosing frequency.

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.

Immediaterelease tablet

Delayedrelease tablet

Extendedrelease tablet

Cumulative amount of drug released

Time

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