Dosage Forms Exam 3

Sterilization

Destruction of living organisms and their spores or their complete removal from the preparation.

Steam Sterilization

Conducted in autoclave, using steam under pressure. Denatures and coagulates essential proteins. Effective for sterilizing bulk solutions, glassware, surgical dressings/instruments.

Steam Temperatures

Max steam temp ~212°F

10lb pressure 240°F for 30 mins

15lb pressure 250°F for 20 mins

20lb pressure 260°F for 15 minsgvfg.

Dry Heat Sterilization

Carried out in ovens and may be heated by gas or electricity → bacterial death due to dehydration of the microbial cell followed by oxidation. Method of choice when dry apparatus/containers are required.

Dry Heat Sterilization Temperature

Less effective than steam, requires higher temp and longer period. Conducted at 150°C-170°C for not less than 2 hours.

Sterilization by Filtration

Physical removal of microorganisms by adsorption on the filter membrane or by sieving mechanism. Used for heat sensitive solutions.

Sterilization by Filtration Advantages

Relatively inexpensive equipment for small-scale. Complete removal of living and dead cells and other particulate matters.

Gas Sterilization

For heat- and moisture-sensitive materials. Exposure to ethylene oxide or propylene oxide gas → alkylation of microbial proteins. Generally sterilized with ethylene oxide gas, requires 4-16 hours of exposure.

Sterilization by Ionizing Radiation

Sterilization can be achieved by exposure to ionizing radiation. Ionization kills by destroying cellular structure and causing mutation.

Disadvantages of Sterilization by Ionizing Radiation

Highly specialized equipment and trained personnel are required. Effect of irradiation on products and their containers.

Pyrogens

Fever-producing metabolic products from the outer cell wall of gram negative bacteria. Removed by oxidation and separated from water by distillation

Rabbit Test

Inject the product into 3 healthy rabbits’ ear veins. If none has a temperature rise ≥0.5°C, it passes. If any does, test 5 more rabbits.

Limulus Amebocyte Lysate (LAL) Test

A fast, inexpensive test that uses horseshoe crab blood extract to detect bacterial endotoxins; it is more sensitive than the rabbit test but may be affected by some drugs.

Topical Dosage Forms

Applied to external body surface to skin or mucous membrane for exerting a local action.

Dermatologicals

Applied to skin and scalp

Semisolid Dosage Forms

Intended for external, topical applications, → skin, eye, nose, vagina, rectum. Mainly intended for local effect, but systemic should be taken into account for pregnant women and nursing mothers.

Ointments

External application to the skin or mucous membrane. May be medicated or non-medicated → made up of drug and ointment base. Soften at body temp, spread easily when applied.

Nonmedicated ointments

Provide protective and lubricating effects.

Ointment bases

The vehicle in which the drug is dispersed. Classified into oleaginous, absorption, water-remove, or water-soluble.

Oleaginous (hydrocarbon) bases

Protect against the escape of moisture. Remain on skin for longer and are effective as occlusive dressings. Hard to wash, wide MPs, good compatibility.

Petrolatum

Yellow petrolatum or petroleum jelly; a purified mixture of semisolid hydrocarbons obtained from petroleum → vaseline.

White petrolatum

White petroleum jelly; decolorized petrolatum

Yellow ointment

A mixture of petrolatum (950g) and yellow was (50g).

White ointment

A mixture of petrolatum and white wax.

Absorption bases

Can absorb appreiable quantities of water or aqueous solutions without marked changes in consistency. Not easily removed by water because the external phase is oleaginous.

Type 1 Absorption Bases

Emulsifiable bases; do not contain water but become w/o emulsion upon incorporation of water.

Type 2 Absorption Bases

Emulsion bases; water in oil emulsions to begin with that allow incorporation of additional water.

Water removable (washable) bases

Oil-in-water emulsions (creams) that are easily removed from skin. Can absorb fair amount of aqueous solution, diluted with water/aqueous solution, non/less greasy and occlusive.

Water soluble (greaseless) bases

No oleaginous bases, completely water washable. Mostly used for incorporation of solid substances.

Incorporation of Drug Powder

The drug is levigated with a small amount of vehicle or a miscible component of the formulation to form a concentrate. The concentrate is then mixed with the remainder of the bases.

Levigation

Process of grinding an insoluble substance to a fine powder, while wet.

Incorporation of Liquids

A small quantity of aqueous solution may be incorporated into oleaginous bases by mixing the solution with a small amt of hydrophilic base then with oleaginous base.

Extemporaneous Preparation (Small Scale)

Mortar and pestle or spatula used to rub the ingredients together on an ointment slab or pill tile or parchment paper.

Large Scale Manufacturing

Stainless steel tank with counter sweep agitation and built-in homogenizer. Ointment roller mill.

Fusion

Ointments having emulsion bases involve both melting and emulsion.

Creams

One or more medications may be dispersed in either w/o emulsion or o/w emulsion or water washable base. Applied in weeping or oozing surfaces, easier to spread and remove.

Pastes

Contain larger amount of solid compared to ointments → stiffer. Good protective barrier, remain in place after application. Opaque, water impermeable, prevent dehydration.

Gels

Semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle rendered jellylike by the addition of a gelling agent.

Two phase gels (Magmas)

Inorganic materials, aqueous medium

Single-phase gels

Natural/synthetic polymers, a liquid

Plasters

Solid or semisolid adhesive masses spread on a backing membrane such as paper, fabric, or plastic. Contain adhesive and provide prolonged contact with the skin.

Medicated plaster

Provide effects at the site of application → cut to size to conform to the surface to be covered.

Unmedicated Plaster

Provide protection or mechanical support at the site of application.

Simple powder

A single chemical substance in powder form.

Pharmaceutical Powder

A mixture of finely divided solids in dry form

Particle size

0.1-1000 μm, most commonly 0.1-10 μm

Granule

A prepared agglomerate of powdered material.

Sieve # and Sieve Opening

As size # increases, sieve opening decreases

Trituration

Comminution in dry state → a rough surface is more effective thann a smooth surface.

Levigation

Comminution with the aid of a liquid (levigating agent → glycerin, mineral oil) in which the powder is insoluble.

Pulverization by intervention

Comminution with the aid of a volatile liquid

Angle of Repose

The angle formed between a pile of powder and a flat surface. Smaller angle means better flow; larger angle means poorer flow.

Bulk Powders

Dispensed in bulk quantities for non potent drugs.

Divided powders

Potent medication powders available as divided powders in individual dosing units based on the amount to be taken or used at a single time.

Aerosol Powders

To treat asthma or other bronchial disorders. Dry powder inhalers and metered-dose inhalers.

Blending

Mixing of two or more powders

Spatulation

Blending small amounts by spatula on sheet of paper or ointment tile. Not suitable for potent substances or large quantities of powders.

Trituration

Used to comminute as well as blend powders. Geometric dilution is used to ensure uniform distribution, especially in potent drugs.

Sifting

Powders are passed through sifters; makes light, fluffy products. Not suitable for mixing potent drugs.

Tumbling

Tumbling in rotating chamber; both small-scale and large-scale mixing, very suitable for mixing potent drugs.

Granules

Prepared agglomerates of smaller particles of powder. Better flow properties, more resistant to humidity, less likely to cake or harden upon standing, easy to wet compared to powders.

Effervescent granules

A special form of granules to provide a pleasant vehicle for drugs with bitter of salty taste. Citric acid, tartaric acid + sodium bicarb = CO2; masks undesirable taste of any medicinal agent.

Dry or Fusion Method

Powder citric acid and mix it with other powders quickly in low humidity. Warm to 34–40°C to release water of crystallization, which binds the powders into a spongy mass; sieve into granules, dry at ≤54°C, and pack.

Wet Method

Granulation method that uses a small amount of aqueous alcohol as a binder to form a pliable mass, which is then granulated and dried. It can be used with anhydrous powders.

Capsules

Solid dosage form, medicinal agent is enclosed within a hard or soft shell of gelatin, primarily intended for oral delivery.

Advantages of Capsules

Tasteless when swallowed, variety of dosage strengths, efficiently and productive manufactured, packaged and shipped at a lower cost. More stable and longer shelf-life than liquids.

Advantages of Hard Gelatin Capsules

Rapid drug release is possible, good barriers to oxygen.

Disadvantages of Hard Gelatin Capsules

Bulky materials are a problem, generally more costly than tablets. Concern over maintaining proper shell moisture content (13-16%), too dry = become brittle/easily fractured, too moist = too soft and gets sticky.

Composition of Hard Gelatin Shells

Gelatin, dyes and other colorants, opacifying agent or opacifier, preservative, water.

Fillers or diluents

Increase the bulk of formulation; lactose, mannitol, starch.

Glidants

To improve the flow from the hopper and into the body of the capsule during the filling process (flowability); colloidal silicon dioxide, starch, talc.

Lubricants

To reduce powder adhesion to the machine parts; magnesium stearates, calcium stearate, stearic acid

Disintegrants

To aid rapid disintegration and dissolution of the contents; sodium starch glycolate, starch, croscarmellose sodium

Surfactants and wetting agents

Increase the wettability of drug particles, and enhance drug dissolution; sodium dodecyl sulfate.

Manufacture of Hard Gelatin Capsules

1. Developing filling contents formulation

2. Selecting the capsule size

3. Capsule filling

4. capsule sealing

5. capsule clean/polishing

Soft Gelatin Capsules

Made with gelatine to which glycerin or polyhydric alcoholic such as sorbitol has been added (as plasticizer).

Advantages of soft gelatin capsules

Can encapsulate and hermatically seal liquids, suspensions, pasty materials, dry powders, and preformed tablets. Pharmaceutically elegant and easily swallowed

Disadvantages of soft gelatin capsules

Generally more costly to product than tablets ot hard shell capsules.

SGC filling content formulation

1. Pure liquids

2. mixtures of miscible liquids

3. solids dissolved or suspended in a liquid vehicle

Water immiscible liquids

vegetable oils, aromatic oils

Water-miscible, non-volatile liquids

Polyethylene glycol (PEG), polysorbate 80

Water-miscible, relatively nonvolatile liquids

Propylene glycol