DRUG DOSAGE FORMS AND DELIVERY SYSTEMS

Dr Muhammad Raza

Dosage forms• Liquid dosage forms

– Solutions– Syrup– Elixir– Suspension– Emulsion

• Solid dosage forms– Powders– Tablets– Capsules

• Topical preparations– Ointments– Creams– Pastes– Gels– Foams

• Parenterals and sterile products– Injectables– Infusions– Irrigation– Douching– Eye and Ear drops

According to route of administration Enteral (GIT) Parenteral (Inj. Im, iv, ip, etc) Inhalation Topical

• Enteral Dosage form– Oral– Sublingual– Rectal

Oral dosage formsSolidsLiquids

Oral liquid dosage forms (Advantages)

Solutions/suspensions/emulsionsThe active agent is homogenously dispersed

throughout the productActive agent in a solution does not need undergo

dissolutionThe dose of active agent is easily and conveniently

adjusted by measuring different volumesMay be swallowed by patients who have difficulty

in swallowing a tablet or capsule e.g. pediatric and geriatric patients

Drugs like KCl that may cause ulceration to mucosa as tablets avoid this if in solution

Oral liquid dosage forms (Drawbacks)

Active ingredients in solution are more susceptible to chemical degradation e.g. hydrolysis

As a consequence of above factor, has a shorter shelf life

Some drugs in liquid form give taste or smell bad enough and present difficulty in swallowing by patient

Liquid forms are heavier and take more shelf space as compared to solids

The accuracy of the dose depends on patient or care-giver measuring the proper volume

Solutions are susceptible to microbes and need preservative that may induce allergy to the patient

A. Oral solutions• USP 26 and National Formulary (NF) 21 categorize oral solutions

liquid preparation, intended for oral administration, that contain one or more substances with or without flavoring, sweetening, or coloring agents dissolved in water or cosolvent-water mixtures.

• Homogenous one phase system or product that has two or more components.

• E.g. simple syrup NF – (Sucrose* + water = homogenous solution)

• *(Sorbitol, Fructose, aspartame are used)

Water is the most commonly used vehicle for drug solutions.The USP recognizes six types of water for the preparation of dosage forms• a. Purified water USP

– obtained by distillation, ion exchange, reverse osmosis.– contain not > 10 ppm of total solid -- have a pH 5 - 7, – used in prescriptions and finished manufactured products except parenteral and

ophthalmic products.• b. Water for injection USP

– obtained by distillation or by reverse osmosis. It conforms to the standards of purified water

– free of pyrogen– used as a solvent for the preparation of parenteral solutions

• c. Sterile water for injection USP – for injection that is sterilized – packaged in single-dose containers of type I and II glass.– not >1 L volume pack

• d. Bacteriostatic water for injection USP• e. Sterile water for inhalation USP • f. Sterile water for irrigation USP

2. Oral drug solutions Include syrups and elixirs as well as other less widely prescribed classic galenical formulations• A. Syrups are traditionally peroral solutions that

contain high concentrations of sucrose or other sugars.

(1) Syrup NF (simple syrup) is a concentrated or nearly saturated aqueous solution of sugar (65% w/v).

(2) Syrups have a low solvent capacity for water-soluble drugs because the hydrogen bonding between sucrose and water is very strong. For this reason, it can be difficult or impossible to dissolve a drug in a syrup.

(3) The sucrose concentration of syrup plays a critical role in the control of microbial growth. At saturation, the syrup becomes self-preserving.

B. Elixirs

Traditionally elixirs– contain alcohol as a cosolvent. Many peroral

solutions are not described as elixirs, but contain alcohol

(1)To be considered an elixir, the solution must contain alcohol. Traditionally, the alcohol content of elixirs has varied from 5%-40%. Most elixirs become turbid when moderately diluted by aqueous liquids.

(2) Aromatic elixir NF, prepared from syrup, contains approximately 22% alcohol.

DR RAZA

Spirits TincturesSpirits are alcoholic or hydroalcoholic solutions of volatile substances, that contain 50%-90% alcohol. e.g., Compound orange spirit, Compound cardamom spiritSpirit ammonia Spirit of camphor

Tinctures are alcoholic or hydroalcoholic

solutions of chemicals or soluble constituents of vegetable drugs. Tinctures are usually considered stable.

The alcohol content of the official tinctures varies from 17%-21% with opium tincture USP

and from 74%-80% with compound benzoin tincture USP. Tincture Iodine Tincture mercurochrome

C. Suspensions (Dispersions of finely divided solid active substances in liquids)

• 1. Lotions, magmas (i.e., suspensions of finely divided material in a small amount of water), and mixtures are all suspensions (e.g., calamine lotion USP, kaolin mixture with pectin NF).

• Some drugs are packaged in a dry form to circumvent the instability of aqueous dispersions. Water is added at the time of dispensing to reconstitute the suspension.

• 2- Purposes of suspension– a. Sustaining effect– b. Stability – c. Taste – d. Basic solubility

DR RAZA

D. Emulsions (Dispersions consisting of two liquids which do not mix with each other)

1. Purposes of emulsions• a. Increased drug solubility• b. Increased drug stability• c. Prolonged drug action• d. Improved taste• e. Improved appearance

2. Phases of emulsions (Two Phases)

– (1) If water is the internal phase, - w/o.– (2) If water is the external phase, - o/w.– a. The liquid droplet is known as the dispersed,

internal, or discontinuous phase– other liquid is known as the dispersion medium,

external phase, or continuous phase.– b. In pharmaceutical applications, one phase is

usually an aqueous solution- The other phase is usually lipid or oily.

E. Ointments1. Ointments Are semisolid substances that are greasy, normally

anhydrous and insoluble in water.Consist of soft paraffin or a combination of soft paraffin with liquid

paraffin and hard paraffin.Anhydrous nature - do not require any preservatives.Advantages - more moisturizing, - more occlusive than

creams - form a protective film over the skin - tend to prolong and enhance drug penetration

They are messy. Because of their marked occlusive effect, ointments are not suitable for

acute weeping, crusting skin conditions, particularly in intertriginous areas.

Ointments are very useful particularly for chronic, dry skin lesions.used as: a. Emollients to make the skin more pliable b. Protective barriers to prevent harmful substances from coming in

contact with the skin c. Vehicles in which to incorporate medication

F. CreamsAre either water-miscible and readily washed-off (O/W), or

oily and not so easily washed off (W/O)Creams are

less messy and less occlusive than ointments, and are suitable for use in the flexural or napkin areas

Preferred form of treatment forexudative dermatoses, and for use under wet dressings

Contain water - liable to fungal & bacterial contamination Preservatives are usually added, may cause skin allergy• Barrier creams (Oily Creams) often contain water-repellent

substances such as dimethicone or other silicones. They give protection against irritation or repeated hydration and is useful in the treatment of napkin rash and bedsores, etc.

• Used in hairy areas, baby buttocks

An emulsion, semisolid dosage form, usually containing > 20% water and volatiles and/or < 50% hydrocarbons, waxes, or polyols as the vehicle

G. Pastes H. GelsPastes: Are stiff preparations

containing a high proportion of finely powdered solids such as zinc oxide and starch.

They are less occlusive than ointments

Used in Subacute, Lichenified, or Excoriated skin conditions

Due to their stiff nature, pastes can be applied accurately to a particular lesion such as

chronic eczema and psoriasis, and are useful for local application of irritating

drugs

Gels: Are clear, sticky, jelly-like semisolids or solids prepared from high molecular weight polymers in an aqueous or alcoholic base.• Alcoholic gels are drying and

cooling and are best suited for acute exudative pruritic eruptions.

• Non-alcoholic gels are more lubricating and are well suited to dry scaling lesions in the scalp.

• Due to their drying effect and especially the alcoholic ones, they may cause irritation and cracking to the skin.

I. Suppositories Solid or semisolid mass intended to be inserted into a body orifice (i.e. rectum,

vagina, urethra). After it is inserted, a suppository either melts at body temperature or dissolves (or disperses) into the aqueous secretions of the body cavity

a. Rectal ---are often used for local effects (hemorrhoids or infection)b. When used rectally, can provide systemic medication. The absorption of a drug through the rectal mucosa into the circulation involves

drug release from a vehicle and diffusion through the mucosa drug transport through the veins or lymph vessels into systemic fluids or tissues. The first-pass effect is avoided because the rectal veins "bypass the liver.“

Rectal suppositories are useful when - oral administration is inappropriate, as with infants- non compliance- debilitated or comatose patients, and - patients who have nausea, vomiting, or - gastrointestinal disturbances (Disease)- disturbances of the GIT by ulceration or irritation induced by drug itself.

Types of suppositories• a. Rectal suppositories --b. Vaginal suppositories• c. Urethral suppositories

Solid Dosage forms (Advantages)• Simple and practical administration • No taste-masking problem• Good possibilities of controlling absorption e.g. by the

use of slow release or enteric coated forms• Accuracy of dosage• Good chemical, physical and microbiological stability • No preservation requirements • Generally more stable than liquids, with longer expiration

dates• Rational manufacture and packaging • Less shelf space needed per dose than for liquid• Easy shipping and handling• Relatively low costs

J. Powders 1. Powders. A pharmaceutical powder is a mixture of finely

divided drugs or chemicals in dry form. The powder may be used internally or externally

a. Advantages of powders • (1) Flexibility of dosage• (2) Good chemical stability of compounding• (3) Rapid dispersion of ingredients because of the small

particle sizeb. Disadvantages of powders • (1) Time-consuming preparation• (2) Inaccuracy of dose• (3) Unsuitability for many unpleasant-tasting, hygroscopic,

and deliquescent drugs

K. Capsules 1. Solid dosage forms in which one or more medicinal or inert

substances are enclosed within a small gelatin shell. Most capsules are intended to be swallowed whole, but occasionally, the contents are removed from the shell and used as a premeasured dose.

• 1. Hard gelatin capsules• (1) Empty capsules are numbered from 000 (largest) to 5 (smallest). Capsules

capacity ranges from 600 to 30 mg for capsules from 000 to 5, respectively. Powder, compact, beads, or granules are filled.

• 2. Soft gelatin capsules• (1) Soft gelatin capsules are prepared from gelatin shells. Glycerin or a

polyhydric alcohol (e.g., sorbitol) is added to these shells to make them elastic or plastic-like. Preservatives are added to prevent the growth of fungi.

• Uses. Soft gelatin shells are oblong, elliptical, or spherical. They are used to contain liquids, suspensions, pastes, dry powders, or pellets

L. Tablets Tablets are the most commonly used solid

dosage forms.

Advantages Precision and low content

variability of the unit dose Low manufacturing cost Easy to package and ship Simple to identify Easy to swallow Appropriate for special-release

forms Best suited to large-scale

production Most stable of all oral dosage

forms Essentially tamperproof

• Disadvantages Some drugs resist compression into

tablets. Some drugs (i.e., those with poor

wetting, slow dissolution properties, intermediate to large doses, optimum absorption high in the gastrointestinal tract, or any combination of these features) may be difficult to formulate to provide adequate bioavailability.

Some drugs (e.g., those with an objectionable taste or odor, those sensitive to oxygen or atmospheric moisture) require encapsulation or entrapment before compression. These drugs are more appropriate in capsule form.

L. Tablets……. types and classes Contd

Classified according to their route of administration, drug delivery system, and form and method of manufacture

(1) Compressed tablets (2) Multiple compressed tablets are layered or

compression-coatedLayered tabletsCompression-coated or dry-coated tables(3) Repeat-action tablets are layered or

compression-coated tablets in which the outer layer or shell rapidly disintegrates in the stomach (e.g., Repetabs®, Schering; Extentabs®, Wyeth).

L. Tablets…….Contd…(4). Delayed-action and enteric-coated tablets• (a) Enteric-coated tablets are coated and remain Intact In the

stomach, but yield their ingredients in the intestines (e.g., Ecotrin, SmithKline Beecham). Enteric-coaled tablets are a form of delayed-action tablet.

(5) Sugar-coated and chocolate-coated tablets (6) Film-coated tablets(7) Air suspension-coated tablets(8) Chewable tablets

(1) Buccal and sublingual tablets• (2) Troches, lozenges, and dental cones(9) Effervescent tablets (e.g., citric acid, tartaric acid, sodium bicarbonate)Tablet excepients • (1) Diluents (2) Binders and adhesives• (3) Disintegrants (4) Lubricants, antiadherents, and glidants• (5) Colors and dyes (6) Flavoring agents• (7) Artificial sweeteners (8) Adsorbents

M. Aerosol products (Inhalers)• 1. Aerosol products, or aerosols, are pressurized dosage

forms. Designed to deliver drug systemically or topically with the aid of a liquefied or propelled gas (propellant).

• 2. Systemic or pulmonary drug delivery is provided by aerosol drug delivery systems, or metered dose inhalers (MDls). These devices allow a drug to be inhaled as a fine mist of drug or drug-containing particles. MDls use special metering valves to regulate the amount of formulation and drug that is dispensed with each dose (i.e. each actuation of the container). Aerosol products are used for topical drug delivery.

• 3. The formulations range from solutions to dispersions.

M. Aerosol products (contd)..• 4. Advantages include• Convenience of push-button dispensing of medication • Stability afforded by a closed, pressurized container • Minimum likelihood of tampering • Protection to the contents from light, moisture, air• Protection from microbial contamination• Aerosol formulations and packaging components (valves,

actuators) permit a wide range of products to be dispensed as sprays, foams, or semisolids.

• 5. Principal disadvantage • is environmental (e.g., disposal of pressurized packages,

venting of propellants to the atmosphere).

N. Controlled-release dosage forms 1. Also known as delayed-release, sustained-action, and extended-release

forms.

Designed to release drug substance slowly to provide prolonged action in the body.2. Advantages of Controlled-release forms Fewer problems with patient compliance Use of less total drug Fewer local or systemic side effects Minimal drug accumulation with long-term dosage Fewer problems with potentiation or loss of drug activity with long-term

use Improved treatment efficiency More rapid control of the patient's condition Less fluctuation in plasma drug level Improved bioavailability for some drugs Improved ability to provide special effects (e.g., morning relief of arthritis

by bedtime dosing) Reduced cost

DR RAZA

O. Sterile Products: Parenteral productsParenteral products are sterile preparations intended for

administration by injection, infusion or implantation into the human body.

Injected through one or more layers of skin. Since they bypass the protective barriers of the body, they must be sterile with regulated pH.

Types of parenterals:1. Ampoules: Made of glass, single use only, opened by breaking the glass• Disadvantages: unsuitable for multiple use, glass contamination by opening of

glass, and other safety considerations2. Vials: Glass or plastic containers, stopperd by rubber, sealed by Alum. grip Designed to hold multiple doses Drugs are easily removed from vials Eliminate the chance of glass particles contamination during dosing Some drugs need immediate reconstitution before use, it accommodates better,

and powders can be lyophilized in vials. Permits rapid reconstitution and dissolution

• Disadvantages: Rubber stopper becomes cored Multiple withdrawals can result in microbial contamination

O. Parenteral products …..contd….• Prefilled syringes and cartridges:• Drugs of emergency atropine, epinephrine etc• Ready to use plastic syringes• Ready to use parenteral packages that improve

accuracy and sterility• Infusion Solution1.Small volume, < 100ml2.Large volumes >100mlSterile aq soln or emulsion with water as the

continuous phase, usually isotonic with blood, intended to be administered in large volumes

O. Parenteral products …..contd….

• Implants: Sterile solid preparation of a size and shape suitable for parenteral implantation and release of active substance(s) over an extended period of time.

• Nasal, ophthalmic and otic preparations: • Sterile aqueous preparations for use into the body

cavities• almost always used for their local effects

P. Patches and Dressings

• Patches, Transdermal: Intended to be applied to the unbroken skin in order to deliver active substance to the circulation.

• However, patches may irritate the skin of some people. • Only drugs to be given in relatively small daily doses can be

given through patches

• Dressing is an adjunct used by a person for application to a wound in order to promote healing and/or prevent further harm. A dressing is designed to be in direct contact with the wound, which makes it different from a bandage, which is primarily used to hold a dressing in place.

bandage

DR RAZA

Adult suppositories

Suppositories for children

Pessaries are solid, bullet-shaped preparations designed for easy insertion into the vagina. They can be inserted using your fingers, or may come with an applicator. Pessaries are normally made of a solid vegetable oil that contains the medicine. The medicine is gradually released into the vagina as the pessary dissolves at body temperature

DR RAZA

Vaginal suppositories

Applicator

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Ampoules

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Vials

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Prefilled syringe

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Eye drops

Spray

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MDIs

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Transdermal patch

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Dressing

Bandages

Controlled Release system:Implanon insertion kitImplantable contraceptive ETONOGESTRIL (PROGESTIN ONLY), 3 YEARS EFFECTIVE

IUD

Infusion bags and admin. set