THE ORIGIN OF DRUGS

MEDICAL UNIVERSITY – PLEVEN

DEPARTMENT OF PHARMACOLOGY







DRUGS & DOSAGE FORMS

Dr G. Stavreva, Dr D. Pendicheva





 THE ORIGIN OF DRUGS

 GALENIC PREPARATIONS (PHYTOMEDICINALS)

 FORMULATION OF DRUG SUBSTANCES

 SOLID DOSAGE FORMS

 LIQUID DOSAGE FORMS

 SEMISOLID DOSAGE FORMS

 AEROSOLS

THE ORIGIN OF DRUGS



Modern drugs, available for use today, are obtained from many sources:

 50% of total prescriptions are composed of synthetic or semisynthetic (based

on natural active ingredients) chemical agents

 25% contain higher plant principles

 12% are microbial-derived products

 7% are mineral in character

 6% are animal-derived



I. Classification of drug sources

1. Natural sources of drugs

1.1. Higher plants: the whole plant, leaves, root, bark, seeds, flowers

1.2. Microorganisms: bacteria, fungi, molds

1.3. Minerals

1.4. Animals: organs, tissues, corporal fluids

2. Synthetic sources of drugs

2.1. Inorganic elements and compounds

2.2. Organic compounds



II. Natural sources of drugs

The discipline of pharmacognosy deals with information on drugs from plant and

animal sources and their constituents.

The plant or animal as a “row material” is composed of many chemical substances,

commonly termed ingredients:

 Active ingredients exert a physiological effect and they are responsible for the

therapeutic activity of the natural drug.

 Inert ingredients have no definite pharmacological activity but their presence

may modify the absorbability or potency of the active constituents.

The term crude drug is usually applied to any part of plant or animal organs, or

whole organisms, either in the fresh state or dried and either grounded or

ungrounded. Natural drugs are used in their crude form, or active

ingredients are extracted and purified for therapeutic use.







2

1. Higher plants

Plants are biosynthetic laboratory for a multitude of chemical compounds:

glycosides, alkaloids, steroids. The active ingredients might be found in any

part (or all parts) of the plant: leaves, root, bark, seeds, fruits, flowers, etc.

2. Microorganisms

Microbial metabolites used as drugs, especially the antibiotics and

antineoplastic agents are produced by fermentation.

 a strain of mold Penicillium chrysogenicum produces Penicillin G

 Clavulanic acid is a product of fungus Streptomyces clavuligerus

 Microorganism from sea water, identified as Cefalosporium

acremonium, gives material for the production of semisynthetic

cephalosporins

 Streptomycine was isolated from a strain of Streptomyces griseus

 Gentamicin is produced by Micromonospora purpurea, an

actinomycete

3. Minerals

 Precipitated sulfur is a very fine powder for external use, acting as

parasiticide, which is used in the treatment of skin disorders

 Purified sulfur is used internally only, as a laxative

 Talc powder is an absorbent, etc.

4. Animals

Animal organs, tissues, fluids and other animal derivatives can be used to

obtain active ingredients:

 Beef and pork pancreas are the source of the natural insulin sold

today

 Exogenous thyroxine can be obtained from the thyroid glands of

animals, usually pigs

 Most commercial preparations of Corticotrophin are obtained from

either hog or sheep pituitary glands

 Vesicular extracts from sheep and bulls are used to yield

prostaglandins



III. Synthetic sources of drugs

In searching for similar activity, many new drugs have been synthesized.

Semisynthetic drugs are based on natural ingredients:

 Reserpine and synthetic antipsychotic agents

 Morphine and synthetic analgesics

 Curare and synthetic neuromuscular blockers

 Adrenaline and amphetamines

Hormones, vitamins, antiepileptic drugs, synthetic antibiotics are only a small

part of the modern drugs, produced by synthesis.



3

Plant Species Popular Crude Active ingredients Pharmacological action Drug

name Drug

Atropa Deadly roots alkaloids: atropine, anticholinergic: antispasmodic,antisecretory, Atropine

Belladonna night shade Radix Belladonnae hyosciamine, hyoscine mydriatic, CNS-activity Scopolamine

(scopolamine)

Datura Jimson weed, leaves alkaloids: atropine, anticholinergic: antispasmodic,antisecretory, Asthma cigarettes

stramonium thorn apple Folium Stramonii hyosciamine, hyoscine mydriatic, CNS-activity

(scopolamine)

Hyosciamus alkaloids: atropine, anticholinergic: antispasmodic, antisecretory, Asthma cigarettes

Niger Henbane leaves hyosciamine, hyoscine mydriatic,CNS-activity

Folium Hyosciami (scopolamine)

Papaverum opium – dried centrally acting analgesics, Morphine

somniferrum Opium poppy exudate of the alkaloids: morphine, codeine, antitussives, Codeine Papaverine

incised seed capsule papaverine smooth muscle relaxant (papaverine)

Digitalis Foxglove leaves cardiac glycosides cardiotonics Digitoxin

Purpurea Folium Digitalis

Digitalis Grecian leaves cardiac glycosides cardiotonics Digitoxin

Lanata Foxglove Folium Digitalis Digoxin

Strophanthus seeds Strophanthin G and K

Gratus et Kombe Semen Strophanthi cardiac glycosides cardiotonics

the overground part

Adonis Pheasant’s eye Herba Adonidis cardiac glycosides mild cardiotonics Adinorm

Vernalis vernalis sedatives

Rauwolfia Chandrika, roots alkaloids: reserpine hypotensive, antipsychotic Reserpine

serpentine Patalagandhi Radix Rauwolfiae

Valeriana roots end rhizome volatile oil, valerenic acid and

officinalis Radix et rhizoma valepotriates sedatives Valeriana

Valerianae

Cinchona bark alkaloids: quinidine, antiarrhythmic, antimalarial, antipyretic Quinine

Cortex Chinae quinine, cinchonine Quinidine



4

GALENIC PREPARATIONS (PHYTOMEDICINALS)

The term “Galenic preparations” is related to classes of natural drug

products obtained from plants by using simplified pharmaceutical procedures.

Such preparations (known as tinctures, extracts, syrups, spirits, aromatic

waters, etc.) popularly have been called galenicals, after Galen, the 2nd

century Greek physician. They are relatively impure products intended only

for oral or external use, which consist of active ingredients in the same

proportion as they are in the crude drug.



I. Tinctures (tinctura, -ae, -ae)

Tinctures are defined as alcoholic or hydroalcoholic solutions derived from

plant crude drugs by maceration (soaking) or percolation (filtering). They are

prescribed in small quantity (10 – 30 g) and are used as drops.

Examples: Tinctura Valerianae; Tinctura Adonidis vernalis, Tinctura Strychni.



II. Extracts (extractum, -i, -a)

Extracts are defined as concentrated preparations of plant drugs obtained by

removal of the active ingredients of the drug with suitable liquids and

evaporation of all or nearly all of the solvent.

Three forms of extracts are recognized:

1. Liquid extracts (extracta fluida) – liquid preparations. Examples:

Extractum Althaeae fl. (Althaea officinalis – hollyhock)

2. Solid or pilular extracts (Extracta solida or spissa) – concentrated

plastic masses, which are suited especially for use in pills, ointments

and suppositories. Example: Extractum Valerianae spissum

3. Powdered extracts (Extracta sicca) – dry powders with contents of

humidity less than 5%. Examples: Extractum Opii siccum, Extractum

Belladonnae siccum.



III. Syrups (Sirupus, -i, -i) – syrups are concentrated solutions of sugar in

water. Types:

1. Simple syrups – contain sugar and water

2. Medicated syrups – contain some added medicinal substances

3. Flavored syrup contains aromatic substances or concentrated fruit

juices (raspberry, cherry, strawberry). Simple and flavored syrups are

useful for preparing liquid oral dosage forms (as Remedium

corrigens).

5

Examples: Sirupus Codeini (antitussiva), Sirupus Rubi idaei (cherry syrup)



IV. Aromatic waters (Aqae aromaticae s. medicatae)

Aromatic waters, also known as medicated waters, are clear aqueous

solutions of volatile oils or other aromatic substances. Their odor or taste is

similar to those substances from which they were prepared. They are used

principally as flavored and perfumed constituents. Examples: Aqua Menthae,

Aqua Rosae, ets.



V. Spirits (Spiritus medicatus) – Spirits are alcoholic solutions of volatile

substances. They are used mainly externally. Examples: Spiritus Mentholi,

Spiritus Lavandulae, ets.





FORMULATION OF DRUG SUBSTANCES.

CLASSIFICATION OF DRUG DOSAGE FORMS

Drug substances and crude drugs are developed into drug dosage

forms in order to optimize stability, safety and effectiveness of drug

substances and to make them suitable for administration. According

to the consistence, they are classified as:



1. Solid dosage forms

2. Liquid dosage forms

3. Semisolid dosage forms

4. Aerosols





SOLID DOSAGE FORMS

Solid dosages, such as tablets, have many advantages over other

types: greater stability, less risk of chemical interaction between

different medicaments, smaller bulk, accurate dosage, and ease of

production.



I. Classification of solid dosage forms

6

1. Powders

2. Tablets

2.1. Tablets for oral administration

 compressed tablets

 buccal tablets

 sublingual tablets

 chewable tablets

 effervescent tablets

 sugar-coated tablets

 film-coated tablets

 enteric coated tablets

 controlled-release tablets

2.2. Tablets for parenteral administration

 tablets for solution

 inserts

 pellets (tablets for implantation)

3. Capsules

 hard gelatin capsules

 soft gelatin capsules

 enteric-coated capsule

4.Granulae

5. Pills

6. Troches



II. Characteristics of solid dosage forms



POWDERS

Historically, powders represent one of the oldest dosage forms.

They posses some advantages: flexibility in compounding and

relatively good chemical stability. The main disadvantages are their

unsuitability for dispensing unpleasant tasting or hygroscopic drugs

and inaccuracy of dose (for bulk powders).



Classification of powders:

1. According to the division into prescribed doses:



7

 bulk powders (Pulveres nondivisi) – all doses are given

inseparably (as a bulk). They may be classified as:

 oral powders – e.g., antacid and laxative powders

 dentifrices

 dusting powders – locally applied nontoxic preparations.

Commercial dusting powders are available in sifter-top

containers and pressure aerosols.

 insufflations – finely divided powders introduced into body

cavities (ears, nose, throat) with a powder blower (insufflator).

Specialized equipment has been developed for the

administration of micronized powders of relatively potent drugs

(e.g., pressure aerosols)

 divided powders (Pulveres divisi) are divided into the

prescribed number of doses and are given orally. Each individual

dose (0.1–1.0 g) should be transferred to a powder paper.

2. According to the composition:

 simplex powders (Pulveres simpliciti) consist of one active

ingredient and suitable inert substances (constituents)

 complex powders (Pulveres compositti) are mixtures of more

than one active ingredient and constituents.



TABLETS

Tablets (tabuletta, -ae) are solid dosage forms containing drug substance

with or without suitable diluents, and prepared by compression. This is the

most frequently used dosage form of administering a drug. They are

swallowed, chewed, or held sublingually. Scoring of some tablets into halves

or quadrants facilitates breaking them if a smaller dose is needed. A tablet’s

color or shape can help identify it. Advantages: simplicity and economy,

stability and convenience in packaging, accuracy of dosage, compactness,

portability, and ease of administration.



Tablet types and their abbreviations:

1. Tablets for oral administration

 compressed (or plain) tablets (CT) – These tablets are formed by

compression and contain no special coating. They are made from

powdered, crystalline or granular materials, in combination with binders,

diluents, etc. (e.g., Analgin, Aspirin, Paracetamol, Saridon, etc.)

 sublingual tablets (linguettae s. tabulettes sublinguales):

8

 are relatively small and dissolve rapidly.

 they are placed under the tongue and allowed to dissolve

 after absorption, the drug enters the systemic circulation without

passing through the portal circulation, thus avoiding first-pass

inactivation in the liver.

 absorption of lipid-soluble molecules through the oral mucosa is rapid

and the effect of drugs given in this way may become apparent within 2

min. Nitroglycerin and organic nitrates are commonly administered by

this route.

 Drugs that are destroyed by the gastrointestinal fluids or are subject to

substantial presystemic metabolism may be formulated into such

tablets.

Examples: Nitroglycerin, Methyltestosterone, Validol, etc.

 buccal tablets (tabulettes buccales) are small, flat, oval tablets,

intended for buccal administration by inserting them into the buccal pouch

(the space between the teeth and the cheek). They are dissolved or

eroded slowly. Example: Desaminooxytocine (Sandopart)

 chewable tablets are large, hard tablets, difficult to swallow, intended to

be crushed before ingesting. Example: Combantrin, Centrum junior, etc.

 effervescent tablets (tabulettes effervescentes) contain sodium

bicarbonate and an organic acid in addition to the drug substance. In the

presence of water, these additives react liberating carbon dioxide which

acts as disintegrator and produces effervescence. These tablets are

soluble and they are taken readily and absorbed rapidly (e.g., Upsarin, Vit

C, Supradin, etc.)

 sugar-coated tablets (SCT, dragee, -s) are smooth, oval compressed

tablets containing sugar coatings. Sugarcoating provides both protection

and sweet taste but the coating operations take a long time. Example:

Nifedipin, Vitaferro, etc.

 film-coated tablets (FCT, film-tabulettae) are compressed tablets which

are covered with a thin layer or a film of polymeric substances to protect

their contents from moisture or to mask the taste of the ingredients.

 enteric-coated tablets (ECT, tabulettes enterosolventes) are coated

with substances that resist solution in gastric fluid but disintegrate in the

alkaline contents of the intestine. Enteric coating is used for drugs with a

gastric irritant action, for drugs which are unstable in the acid medium of

the gastric contents or if the drug should act on the intestine. (e.g.,

Voltaren, Salazopyrin).







9

 controlled-release tablets are formulated to release the drug slowly over

a prolonged period of time. These dosage forms have been referred to as

prolonged-release (PR) or sustained-release (SR) dosage forms as well.

2. Tablets for parenteral administration

 inserts are intended for insertion into body orifices. Metronidazole,

Isoconazole, Clotrimazole are vaginal tablets (tabulettes vaginales).

 pellets (tablets for implantation) are small, sterile tablets, used by

implantation when prolonged and continuous absorption is desired

(Estradiol, Disulfiram, etc.)

 tablets for solutions are used for preparing solutions for external use



CAPSULES

Capsules (capsula, -ae) are solid dosage forms in which the drug substance

is enclosed in either a hard or soft soluble container of suitable form of

gelatin. They are intended to mask the smell and taste of the drug substance.

Capsules are tasteless, easily administered and some patients prefer them to

the tablets.

1. Hard gelatin capsules (capsulae gelatinosae durae s. operculatae),

also referred to as dry-filled capsules (DFC), consist of two sections, one

slipping over the other, thus completely surrounding the drug formulation.

Commercially filled capsules have the conventional oblong shape.

2. Soft elastic capsules (SEC; capsulae gelatinosae molles s. elasticae)

are soft, globular, gelatin shells somewhat thicker than that of hard gelatin.

They may be round, oval, oblong, or tube-shaped and the contents may

be liquid, paste, or powder. Oil-soluble drugs, (e.g. vit A, E) can be

administered in SEC.

3. Enteric-coated capsules remain intact in the stomach, but dissolve and

release the contents of the capsule once it reaches the small intestine.

They delay the release of drugs which are inactivated by the stomach

contents or may irritate the gastric mucosa. Enteric coatings are prepared

of synthetic polymers.



PILLS

Pills (pilula, -ae) are small, round dosage forms for oral administration which

are prepared by the pharmacist. They are rarely prescribed today. The

powdered ingredients are mixed together with binding agents and solid

extracts (excipiens, -entis) and made into a plastic mass (massa pilularum).

The pill mass is rolled into spheres and coated with talc, gelatin, or sugar.



TROCHES



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Troches (lozenges or pastilles) are discoid-shaped oral forms containing a

drug substance in a flavored base. They are placed in the mouth where they

slowly dissolve, liberating the active ingredient. The drug involved can be

antiseptic, local anesthetic, antibiotic, antitussive, or decongestant.



GRANULES

Granules (granulae) are dosage forms related to powders. They are

particularly suitable for the preparation of solutions or mixtures of drugs, such

as antibiotics, that are unstable in the presence of water.

Effervescent granules contain sodium bicarbonate and citric acid or tartaric

acid in addition to the active ingredients. On solution in water, carbon dioxide

is released. These forms mask the unpleasant taste and ensure better

absorption of the medications.



PRESCRIPTION WRITING



Rp./ Nitroglycerini 0,5 mg

Da scatulam № 1 in linguettis

Signa (Scribe). Place 1 tablet under tonge.

#

Rp./ Aspirni Protect 100 mg

Da scatulam № 1 in tabulettis entreosoventis

S. Take 1 tablet daily.

#

Rp./ Aspirni C

Da scatulam № 1 in tabulettis effervesentibus

S. Take 1 tablet 3–4 times daily, dissolved in 250 ml water.

#

Rp./ Tabulettarum Analfini 500 mg

(Tabl. Analgini 500 mg)

Da scatulam № 1.

S. Take 1 tablet 3–4 times daily

#

Rp./ Isoptini SR 120 mg

D. scat. № 1 in film-coated tablets.

S. Take 1 tablet daily at 8:00 a.m.

#

Rp./ Аllergosani 25 mg

Da scatulam № 1 in dragées.

(Da scatulam № 1 in sugar-coated tablets)

Signa. Take 1 tablet 3–4 times daily.

11

#

Rp./ Amoxicillini 1 g

D. scat. № 1 in capsulis (caps.).

S.Take 1 capsules every 8 hours for 5 days.

#

Rp./ Pulv. Natrii hydrocarbonatis 50 g

D. S. Take 1 teaspoon 1 hour after meals and bedtime.

#

Rp./ Codeini phosphatis 10 mg

Sacchari lactatis 300 mg

M. f. pulvis. D. t. d. № 20

S. Take 1 powder 3 times daily.

#

Rp./ Pulveris dermatici Topocini 5 g

(Pulv. derm. Topocini 5 g)

D. scat. № 1.

S. For external application.

#

Rp/ Flac. Zinnati 125 mg/5 ml – 60 ml

(Granulorum Zinnati 125 mg/5 ml – 60 ml)

(Suspensionis Zinnati 125 mg/5 ml – 60 ml)

Da. Signa. 2 ml every 12 hours (for baby with body mass 10 kg)







LIQUID DOSAGE FORMS

I. DEFINITION OF LIQUID DOSAGE FORMS



Liquid dosage forms are prepared by dissolving the active

ingredient(s) in an aqueous or nonaqueous solvent, by suspending the

drug in appropriate medium or by incorporating the drug substance into

one or two phases of an oil and water system.

These forms can be formulated for different routes of administration:

oral use, introduction into body cavities , or applied externally.

The oral liquid forms can be readily administered to children or people

unable to swallow tablets or capsules.

The absorption rate of oral dosage forms decreases in the following

order: aqueous solution > aqueous suspension > tablet or capsule.

Drug substances are less stable in aqueous media, than in the solid

12

dosage forms and it is important to properly stabilize and preserve

them. There is a risk of chemical interactions and microbial

contamination for some of the products.



II. CLASSIFICATION OF LIQUID DOSAGE FORMS

1. Solutions (solutio, – onis, -ones)

 aqueous solutions

 nonaqueous solutions

2. Emulsions (emulsio, -onis, -ones)

3. Suspensions (suspensio, -onis, -ones)

4. Mucilages (mucilago, -inis, -ines)

5. Liniments (linimentum, -i, -a)

6. Infusions and decoctions (infusum, -i; decoctum, -i)

7. Drops (guttae, -arum)

8. Mixtures (mixtura, -ae, -ae)

9. Sterile dosage forms for injection

 ampoules (ampulla, -ae)

 vials (flacon, -is)

 bottles (olla, -s)

 prefilled disposable syringes (or pre-filled syringes)



II. CHARACTERISTICS OF LIQUID DOSAGE FORMS



SOLUTIONS

Solutions (solutio, -onis, -ones) are homogeneous mixtures that are

prepared by dissolving a solid, liquid, or gas in another liquid. The molecules

of the dissolved substance are dispersed among those of the solvent. Many

pharmaceuticals are simply solutions of a medicament in water, alcohol,

ether, glycerin, oils, or some other solvent. Various aromatic waters (e.g.,

chloroform or peppermint water) may also be used as solvents. Solutions are

intended for internal, external, and parenteral administration.

1. Aqueous solutions include those pharmaceutical forms that are prepared

with purified water (aqua destillata – deionized, demineralized water) or

aromatic water as a solvent. Simple solutions for oral administration,

douches, enemas, gargles, mouthwashes, nasal and otic solutions are

assigned to this category.

2. Nonaqueous solutions are the alcoholic and hydroalcoholic solutions,

ethereal solutions, glycerin solutions, etc.



13

Solutions may be prepared in bulk or as single-use packages, and they are

usually bottled automatically (few of them can be prepared extemporally).



EMULSIONS

Emulsions (emulsio, -onis, -ones) are two-phase systems in which one

liquid is dispersed throughout another liquid in the form of small droplets.

They are classified as:

 oil-in-water (O/W) emulsion – oil is the dispersed phase and an aqueous

solution is the continuous phase

 water-in-oil (W/O) emulsion – an aqueous solution is the dispersed phase

and oil is the continuous phase

These forms can be administered orally, topically, or parenterally

(intramuscularly). Specialized uses include emulsions for intravenous feeding

of lipid nutrients (Intralipid). Other radiopaque emulsions are used as

diagnostic agents for X-ray examinations.

Emulsions are thermodynamically unstable. They appear white and tend to

separate on standing. In order to prepare suitable emulsions and to have

them remain stable for a suitable period of time, a number of emulsifying

agents are used in their preparation. They can be natural substances (acacia

or Gumma arabicum, tragacanth, pectin, gelatin, egg yolk, lecithin, etc.),

finely divided solids, or synthetic agents.



SUSPENSIONS

Suspensions (suspensio, -onis, -ones) are two-phase systems

consisting of a finely divided solids dispersed in liquids. If the drug

is insoluble or poorly soluble, a suspension may be the most

suitable dosage form. The taste of drugs can be improved if they

are supplied in suspension form rather than solutions. Suspensions

may be formulated for oral, parenteral (intramuscular or

intraarticular) or topical administration. Antibiotic granules are

generally used for preparation of suspensions in pediatric practice.

Well formulated suspensions should posses certain basic

properties. The dispersed phase should settle slowly, if at all

possible, and be dispersed readily on shaking.

The main ingredients in a suspension are:

 a drug

 natural viscosity agents (natural gums and cellulose derivatives)



14

 an external medium – it is usually water for oral preparations; or

other polar liquids (glycerin, alcohol)



MUCILAGES

Mucilages (mucilago, -inis, -ines) are thick, viscid, adhesive

liquids, produced by dispersing gum in water, or by extracting the

mucilaginous principles from plant substances with water (Gumma

arabicum, Radix althaeae, etc.). They are unstable and should

never be made in quantities larger than those that can be used

immediately, unless a preservative is added.

Mucilages are used primarily to prevent immediate sedimentation of

insoluble substances in liquids. They can prevent mucous irritation

caused by some drug substances (e.g., Chlorali hydras).



INFUSIONS AND DECOCTIONS

Infusion (infusum, -i, -a) is a dilute solution of the readily soluble

constituents of crude drugs (from the soft parts of plants). Fresh

infusions are prepared by macerating the drugs for a short period of

time (15 min) with boiling water.



Decoction (decoctum, -i, -a) are extracts of the water-soluble and

heat-stable constituents from crude drugs (from the hard parts of

plants) by boiling in water for 30 min, and cooling.

These forms are of short duration and should never be administered

in quantity for more than 3 days.



DROPS

Drops (guttae, -arum) are solutions, tinctures, or mixtures of high-

potent drug substances. These forms are intended to be

administered internally or externally (as eye drops or collyrium,

nasal, and otic drops). Drops are prescribed in small quantity (10 –

30 g). For officinal forms, the right number of drops per 1 ml of liquid

have to be labeled.



MIXTURES



15

Mixtures (mixtura, -ae, -ae) are multicomponent liquid containing

two or more active ingredients, dissolved, suspended, or dispersed

in a suitable liquid base (water, alcohol, glycerin, aromatic water, or

infusions and decoctions). Some mixtures may contain tinctures.

Suspended solids may separate slowly on standing, but are easily

redispersed on shaking (shake mixtures – mixturae

agitandae).Syrups are added as Remedium corrigens, in quantity of

20% of the total volume (30% for children). Mixtures are unstable

dosage forms with short duration and they are subject to

contamination by microorganisms during the period of their use.



STERILE DOSAGE FORMS FOR INJECTION

Sterile dosage forms for injection differ from all other drug dosage forms

because of their unique use for injection directly into body tissue through the

primary protective systems of the human body, the skin and mucous

membranes. Therefore, they must be exceptionally pure and free from

contaminants.

Injections may be classified in several categories:

1. Solutions ready for injection

2. Dry, soluble products ready to be combined with a solvent just prior to

administration (ex tempore)

3. Suspensions ready for injections

4. Emulsions

5. Liquid concentrates ready for dilution prior to administration

These injections may be administered by such routes as intravenous,

subcutaneous, intradermal, intramuscular, intraarticular, and intrathecal. The

nature of the product will determine the route of administration. Suspensions

would not be administered directly into the blood stream because of the

danger of insoluble particles blocking capillaries. Unstable emulsions, if

injected intravenously may cause lipid embolism (excluding some forms with

special characteristics). Hypertonic solutions are administered only

intravenously. When compared with other dosage forms, injections possess

certain advantages:

1. They provide drugs for immediate action

2. The therapeutic dose is adjusted more accurately and readily

3. Drugs can be administered parenterally in cases of unconscious or

uncooperative state of the patient, or because of lack of absorption from

the GIT.

Among the disadvantages are requirement of asepsis, pain factor, risk of

local irritation, difficulty in correcting the error.

16

Parenteral products are packaged in ampoules, vials, bottles, plastic

bags, and prefilled disposable syringes. Containers for injections can be

made of glass or thermoplastic polymers. They may range in size from 1000

ml bottles to 1 ml or less ampoules, vials, or syringes. Each vial is sealed

with a rubber closure held in place by an aluminum cap.

The most widely used solvent for parenteral preparations is sterile water for

injection (aqua redestillata or bidestillata – pyrified water rendered sterile and

pyrogen-free by repeated distillation). Other common solvents include sodium

chloride injection, peach oil (for water-insoluble drugs), etc.



PRESCRIPTION WRITING



Rp./ Sol. Natrii citratis 4% 150 ml

D. S.Take 1 tablespoon 3 times daily.

#

Rp./ Pulv. Natrii citratis 6 g

Aquae destillatae ad 150 ml

Misce. Da. Signa.Take 1 tablespoon 3 times daily.

#

Rp./ Infusi radicis Primulae 6 g/180 g

Ephedrini hydrochloridi 300 mg

Liquoris Ammonii anisati

Natrii benzoatis aa 3 g

M. f. mixtura.

D. S. Take one tablespoon 3 times daily.

#

Rp./ Tincturae Valerianae 20 g

(T-rae Valerianae 20 g )

D. S. Take 20 drops 3 times daily.

#

Rp./ Solutionis Xylometazolini 0,1% 10 ml

(Sol. Xylometazolini 0,1% 10 ml)

D. t. d. № 1 in flaconis (fl.).

S. Put 2 drops into nose 3 times daily.

#

Rp./ Penicillini G 1 000 000 IU

(Benzylpenicillini 1 000 000 IU)

D. t. d. № 20 in fl.

S. 500 000 IU i.m. every 8 hours (after dissolving in 5 ml distilled water).

#

Rp./ Solutionis Lydoli 5% 2 ml

17

(Sol. Pethidini 100 mg/2 ml)

Da tales doses № 10 in ampullis.

Signa. 2 ml every 6 hours i.m.

(on the yellow prescription form)

#

Rp./ Sol. Diazepami 10 mg/2 ml

D. t. d. № 5 in amp.

S. 1 or 2 ml intravenously slowly (5 min)

diluted with 20 or 40 ml 40% glucose.

(on the green prescription form)

#

Rp./ Fraxiparini 0.3 ml

(Nadroparini 0.3 ml)

D. t. d. № 10 in pre-filled syringes.

S. 0.3 ml per day subcutaneously in

the area of the navel for 7–14 days.







SEMISOLID DOSAGE FORMS

Semisolid dosage forms include ointments, liniments, gels,

suppositories, plasters, and plaques.



I. CLASSIFICATION OF SEMISOLID DOSAGE FORMS



1. Ointments (unguentum, -i, -a)

 ointments (unguentum, -i, -a)

 creams (creme, -ores)

 pastes (pasta, -ae, -ae)

2. Gels (gel, -i)

3. Liniments (linimentum, -i, -a)

4. Suppositories (supositorium, -i, -a)

 rectal suppositories (suppositoria rectalia)

 vaginal suppositories (suppositoria vaginalia)

 urethral suppositories (suppositoria urethralia)

5. Plasters

 medicated plasters (emplastrum, -i, -a)

18

 transdermal delivery systems (TTS)

6. Plaques



II. CHARACTERISTICS OF SEMISOLID DOSAGE FORMS



 OINTMENTS (unguentum, -i, -a) are semisolid preparations intended

for external application to the skin or mucous membranes; usually, but

not always, they contain medicinal substances.

The types of ointment bases used as vehicles (vehiculum, basis unguenti)

are selected for optimum delivery of the drug. Ointment properties vary, since

they are designed for specific use, ease of application, or extent of

application.

Oleaginous bases are described as ointments, emulsion bases may be

termed creams, and the forms containing large amounts of solids are termed

pastes.

 Ointment bases (vehiculum, basis unguenti) should be nonirritating,

easily removable, nonstaining, stable, non-pH-dependent and widely

compatible with a variety of medicaments. They are categorized into

four classes:

1. Oleaginous bases: vegetable fixed oils: olive oil, almond oil, sunflower

oil; animal fats; minerals:Vaseline (vaselinum), and paraffin (hard paraffin,

paraffinum solidum; liquid paraffin, paraffinum liquidum). Bases of this type

are occlusive, nearly anhydrous and provide an optimum stability for

medicaments.

2. Absorption bases: anhydrous lanolin (lanolinum anhydricum, sheeps

wool fat). It contains not more than 0,25% of water. It is suitable whenever a

large volume of aqueous solutions must be incorporated into the ointment.

Lanolin (lanolinum) – anhydrous lanolin is converted to lanolin by the

addition of 30% water. It is good emollient and protectant.

3. Emulsion bases: most commonly used type of ointment bases. The oil

phase is typically made up of Vaselinum and/or liquid petrolatum (Paraffinum

liqidum).

4. Water-soluble bases – they are generally prepared of polyethylene glycol.



TYPES OF OINTMENTS:



1. OINTMENTS (UNGUENTUM, -I, -A) are prepared of solid active

ingredients (1–25%), finely powdered and then incorporated into the

oleaginous base. According to the way of administration they can be:



19

ointments for skin application (unguenta dermatica: 20–100 g), eye ointments

(unguenta ophthalmica: 3–10 g), nose ointments (unguenta nasalia), etc.



2. PASTES (PASTA, -AE, -AE) contain powders dispersed in the vehicle in

quantity more than 25%. They are usually stiffer, less greasy and more

absorptive than ointments. Pastes adhere reasonably well to the skin and

they are suited for application on and around moist lesions. Pastes are less

macerating than ointments. They easily may be removed from the skin. They

are divided into pastes for application on the skin (pastae dermaticae) and

dental pastes (pastae dentifricae). An official paste is the Zinc Oxide paste.



3. CREAMS (CREME, -ORES) are similar to ointments but they contain a

water phase (water, aromatic water, etc.). They are classified as:

 cold creams with roughly dispersed water phase and cooling properties

 emollient creams with finely dispersed water phase, which soften the skin.



4. GELS or jellies (gel, -i) are semisolid dosage forms with high degree of

clarity, ease of application and ease of removal and use. The active

ingredients are incorporated into water-soluble bases. The gels often provide

a faster release of drug substance as compared to creams and ointments.

Gel formulations include ophthalmic preparations of pilocarpine, carbachol;

topical preparations for burn therapy; anti-inflammatory treatment; treatment

of acne, etc. Depending on their ingredients some gels may function as

protective coatings. Gels are prepared in adhesive forms in order to increase

the contact time of the active ingredients, e.g., topical dosage forms for

aphthous stomatitis.



LINIMENTS

Liniments (linimentum, -i, -a) are thick, viscid liquids, emulsions,

suspensions, etc. They are intended for external application. They usually are

applied with friction and rubbing onto the affected area. The oily liniments are

milder in their action but are more useful when massage is required.



SUPPOSITORIES

Suppositories (suppositorium, -i, -a) are solid dosage forms of various

weights and shapes for insertion into the rectum, vagina, or the urethra. After

insertion, suppositories soften, melt, and dissolve in the cavity fluids.

Suppository vehicles (bases) can be classified into two types: fatty (e.g.,

Cocoa butter) and water soluble (e.g., polyethylene glycol). Cocoa butter is a

naturally occurring triglyceride, being solid at room temperature and melting

quickly at body temperature.

20

Types: (1) Rectal suppositories (suppositoria rectalia) are administered

rectally either to treat local conditions such as hemorrhoids or to achieve

systemic absorption (sedatives, tranquilizers, and analgesics).

Rectal suppositories can be used when the patient is enable to take

medication by mouth, or when the patient is unconscious. The lower, middle

and upper hemorrhoidal veins surround the rectum. Only the upper vein

conveys blood into the portal system, thus drugs absorbed into the lower and

middle hemorrhoidal veins will bypass the liver. Disadvantages to the use of

rectal suppositories include possible uncertain, local irritation and possible

accidental loss of the medication.

(2) Vaginal suppositories are applied vaginally for a local effect.

Following intravaginal administration, some drug absorbtion from the intact

vaginal mucosa is likely.

(3) Urethral suppositories (suppositoria urethralia) are cylindrical

dosage forms, administered urethrally to treat local conditions. They are

unusual dosage forms.



PLASTERS

Plasters (emplastrum, -i, -a) are substances intended for external

application made of such materials and of such consistency as to adhere to

the skin. They are intended to protection and support and/or to bring

medication into close contact with the skin.

 adhesive plasters

 medicated plasters are used for local or regional drug delivery

 transdermal delivery (or therapeutic) systems (TTS) are used for long-

term systemic delivery of therapeutic agents through the skin (e.g.,

antihypertensive, antianginal, analgesic, steroidal and contraceptive drugs).

Examples: Nitroderm TTS, Estraderm TTS, Durogesic, etc.



PLAQUES

Plaques are special devices for local controlled, prolonged drug therapy,

which are intended for application under the eyelid or in the conjunctival sac

of the eye (plaques used in the treatment of glaucoma) or on the palate

(plaques with antifungal action).







AEROSOLS (SPRAY)

These drugs are designed to carry the drug into the respiratory tree of the

patient or on the skin and mucous (nasal, etc.). According to the chemical

21

characteristics, they are categorized in three groups: gases (nitrous oxide,

oxygen), vapors of volatile liquids (ether, halothane, chloroform), and

aerosols (sprays).



Aerosols are heterogeneous systems consisting of very finely subdivided

liquid or solid particles (optimum size 0,5–3 μm) dispersed in a gas medium.

The pressurized aerosol packages contain different propellants (compressed

gases) driving the drug in the form of mist or foam. They can be inhaled

(nasally or orally) or applied topically to dispense a variety of agents for

treatment of systemic and topical diseases. Metered dose inhalers (with a

metering valve) contain multiple doses and they are intended for delivering

measured quantities of drug. Examples: Salbutamol, Salmeterol, Fenoterol,

etc.

Powders may be administered by mechanical devices that require manually

produced pressure and a deep inhalation by the patient (e.g., Cromolin

sodium).

Nebulizers are devices used for administration of solutions giving sufficiently

small droplets. Nebulised solutions may be breathed directly or by a plastic

face mask or a tent.

Advantages: rapid onset of action; bypass the hepatic circulation; avoidance

of degradation in the gastrointestinal tract; lower dosage that minimizes

adverse reactions; simple, convenient and acceptable therapy.



PRESCRIPTION WRITING



1. Ointments

Rp./ Acidi borici 1,0

Vaselini albi ad 20,0

Msce fiat unguentum.

D. S. Apply twice daily to the affected skin. Not for children under 3

years.

#

Rp./ Unguenti dermatici Acidi borici 5% 18,0

D. tub. № 1.

S. Apply twice daily to the affected skin. Not for children under 3 years.

#

Rp./ Ung. derm. Gentamycini 0,1% 15,0

D. tub. № 1.

S. Apply twice daily to affected skin.

#

Rp./ Unguenti ophthalmici Gentamycini 0,3% 5,0

22

(Ung. Ophth.) Gentamycini 0,3% 5,0

D. tub. № 1.

S. Apply in the lower conjunctival sac of the affected eye twice daily.

#

Rp./ Ultraproct 15,0

(Ultraproct 15 g)

D. tub. № 1.

S. Apply rectally in the evening.



2. Pastes

Rp./ Acidi salicylici 2,0

Zinci oxydi 25,0

Vaselini 48,0

M. f. pasta.

D. S. Apply externally to the burned area once daily.

#

Rp./ Pastae Zinci 25,0

D. tub. № 1.

S. Apply externally to the burned areas once daily.



3. Gels

Rp./ Geli Troxevasini 2 % 40,0

D. tub. № 1

S. Apply twice daily to the affected area (for treatment of varices).



4. Creams

Rp./ Creme Clotrimazoli 1% 20,0

D. tub. № 1.

S. Apply externally to the affected area.



5. Liniments

Rp./ Olei Lini

Aquae Calcis aa 50,0

M. f. linimentum.

D. S. Apply to the burned area.



6. Suppositories

Rp./ Paracetamoli 150 mg

(Paracetamoli 0,150)

D. scat. № 1 in supp.

S. Insert 1 suppository into rectum twice daily.

23

#

Rp./ Morphini hydrochlorici 0,01

Butyri Cacao q. s.

M. f. supp.

D. t. d. № 3.

S. Insert 1 supp. into rectum in case of pain.

#

Rp./ Doloproct

D. scat. № 1 in supp.

S. Insert 1 supp. into rectum in the evening.



7. Plasters

Rp./ Nitrodermi TTS 25 mg

D. scat. № 1

S. Stick 1 plaster daily on the precordial area.



8. Aerosols

Rp./ Ventolini inhaler 0,1 mg

D. t. d. № 1 in flac.

S. For inhalation in case of asthma attack.

#

Rp./ Bicromati 20,0

D. scat. №1 in caps.

S. Inhale 2 capsules every 12 hours, with spinhaler.



EXTEMPORANEOUS PRESCRIPTIONS

1. Antacid powder with anaesthesine (benzocaine)

Rp./ Anaesthesini

Bismuthi subnitratis aa 3,0

Magnesiae oxydi 40,0

M. f. pulvis.

D.S. Half a teaspoon to be taken with meal.



2. Powder with caffeine for general refreshment

Rp./ Coffeini puri 0,05

Sacchari albi 0,2

M. f. pulvis

D. t. d. № 20

S. Take one powder each morning and at lunch-time.



24

3. Bourget powder with antiacid action

Rp./ Natrii bicarbonatis 8,0

Natrii phosphatis 4,0

Natrii sulfatis 2,0

M. f. pulv.

D. t. d. № 10

S. 1 powder to be dissolved in 1 l of water. Drink 1 tea-cup half an hour

before meal.



4. Emulsion with laxative action

Rp./ Olei Ricini 20,0

Gummi arabici 10,0

Aquae destillatae ad 200,0

M. f. emulsion.

D. S. To be taken all at once.



5. Spasmolytic drops with atropine (for 7 days)

Rp./ Atropini sulfatis 0,01

Aquae destillatae ad 20,0

M. D. S. Take 20 drops 3 times daily.



6. Eye drops with Pilocarpine

Rp./ Sol. Pilocarpini hydrochloridi 2% 10 ml

D. t. d. № 1 in flac.

S. Place 1 drops in each eye 3 times daily.



7. Drops for treatment of abdominal colics

Rp./ Dionini (Aehylmorphini)

Papaverini hydrochlorici

Extr. Belladonnae aa 0,2

Aquae Laurocerasi 20,0

M. D. S. Take 20 drops 3 times daily.



8. Mixtura nervina (for 7 days)

Rp./ Natrii bromatis

Kalii bromatis aa 6,0

T-rae Valerianae

T-rae Adonidis vernalis aa 10,0

Coffeini-Natrii benzoatis 1,0

Phenobarbitali-Natrii 0,6

Sirupi Menthae 60,0

25

Aquae destillatae ad 200,0

M. D. S. Take 1 tablespoon 3 times daily, after meals.



9. Suppositories with morphine (with systemic action)

Rp./ Morphini hydrochloridi 0,01

Butyri Cacao q. s.

M. f. supp.

D. t. d. № 6.

S. Insert 1 supp. into rectum in case of pain.



10. Liniment for treatment of burning

Rp./ Olei Lini

Aquae Calcis aa 50,0

M. f. linimentum.

D. S. Apply to the burned area.









26