LIQUID MEDICINAL FORMS

LIQUID MEDICINAL FORMS (infusions, decoctions, emulsions, mixtures, tinctures, liquid extracts, new-Galen’s preparations). MEDICINAL FORMS FOR INJECTIONS

 

Liquid medicinal forms (infusions, decoctions, emulsions, mixtures, tinctures, liquid extracts, new-Galen’s preparations)

 

Infusions

Valeriana officinalis

 

Infusion (infusum – nominative singular, infusa – nominative plural, infusi – genitive singular). These are aqueous extracts from plant raw material; which are obtained by the way of drawing the grinded, dried leaves, flowers, herbs on the water bath or by the way of soling extracts. Infusions frequently are prescribed for internal use and rarely – for external use (for example, for throat gargling). Infusion for internal applications are dosed by table-spoons, dessert-spoons and tea-spoons. They are written out on such method: after the word Rp. it is necessary to write down infusi (inf.), then indicate what parts of the plants are used for preparing infusion (herbs, flowers, leaves), the name of medicinal herb (from capital letter), the raw material quantity and the infusion quantity. Then we must write down D.S. and the way of use. The common dose of medicinal raw material and quantity of infusion are calculated basing on the single dose, the common number of receptions and the volume for one reception.

 

 For example, it is necessary to prescribe infusion of Thermopsis herb, which has to be taken for one table-spoon three times a day during three days (the common number of receptions will be 9). We need to take 135 ml (1 table-spoon includes 15 ml, but 9 table-spoons include 135 ml). According to Pharmacopoeia infusion of Thermopsis herb is made using correlation that 1 part of raw material is for 400 parts of infusion. It means that 400 ml of infusion are prepared using 1 g of the herb. For manufacturing infusion in quantity 135 ml it is necessary to take 0,33 gr. of the herb:

  1 – 400

  X – 135;     X = 0 33

  Prescription looks like this:

              Rp.: Inf. herbae Thermopsidis ex 0,33 135 ml

                     D.S. In 1 table-spoon three times a day

  Sometimes, as above, it is noted in prescription the quantity of raw material for preparing infusion.

              Rp.: Inf. foliorum Uvae ursi 200 ml

                      D.S. In 1 table-spoon three times a day.

 

In those cases drug-store is directed using such instructions of Pharmacopoeia: Infusions from medical plants with strong acting substances are prepared using correlation 1 : 400 (for example, folia Digitalis – Foxglove leaves, radix Ipecacuanhae – roots of Ipecacuanha, herba Thermopsidis – Thermopsis herb).

Digitalis purpurea

 

Secale cornutum

 

  Infusions from medical plants with less intensive action are prepared using correlation 1 : 30 (for example, Adonidis vernalis – Adonis herb, rhizoma Valerianae – rhizome Valerian, Secale cornutum), other infusions – with correlation 1 : 10.

  There are also officinal infusions like: Inf. Valerianae, Inf. Sennae compositum and others.

               Rp.: Inf. Valerianae 120 ml

                      D.S. In 1 dessert-spoon four times a day.

  Infusions are the labile medical forms, that why they are prescribed only for 3-4 days.

 

Decoctions

 

 

  Decoctions – Decocta (decoctum – nominative singular, decocti – genetive singular) are the liquid medical forms which are also obtained by the way of water extracting acting substances from plant material on the water bath or by the way of solving the concentrates.

Quercus robus

 

Mentha piperita

 

Decoction is a method of extraction by boiling, of dissolved chemicals, from herbal or plant material, which may include stems, roots, bark and rhizomes. Decoction involves first mashing, and then boiling in water to extract oils, volatile organic compounds, and other chemical substances.

For preparation decoctions we usually use roots, rhizome or cortex. Decoctions are easy broken that’s why they had to be prescribed only for 3-4 days and kept in the cold place.

 

They are written out like this:

                Rp.: Dec. corticis Quercus ex 10,0 100 ml

                        D.S. For rinsing out mouth.

  Chemist shop prepares decocts with correlation 1 : 10 when it is not noted in the prescription the quantity of plant raw material. Except of the decoction from Senega root (radix Senegae) what is made using correlation 1 : 30.

 

Emulsions

  Emulsions (emulsum – nominative singular, emulsi – genitive singular) are liquid pharmaceutical form, two-phase system with dispersion phase like unsolvable in water liquid, fat or ether oils, balsams. The disperse medium is offered by water. The emulsions are represented by the stable suspensions of the fat-drops in water. There is two kinds of emulsions such as: seminal (Emulsa seminalia) and oil (Emulsa oleosa).

  Seminal emulsions are preparing from the seeds of some medicinal plants: sweet almond (semen Amygdali dulcis), poppy (semen Papaveris), pumpkin (semen Cucurbitae), some nuts (semen Arachidis hypogaea) and others.

  For receiving seminal emulsions are taken 1 part of the pounded seeds on every 10 parts of emulsions.

  Composition of each seed kind includes not only fats but also specific substances – emulsifiers. That’s why there is no need to introduce the emulsifiers into the seminal emulsions.

Emulsions are part of a more general class of two-phase systems of matter called colloids. Although the terms colloid and emulsion are sometimes used interchangeably, emulsion should be used when both the dispersed and the continuous phase are liquids. In an emulsion, one liquid (the dispersed phase) is dispersed in the other (the continuous phase). Examples of emulsions include vinaigrettes, milk, mayonnaise, and some cutting fluids for metal working. The photo-sensitive side of photographic film is an example of a colloid.

 

A. Two immiscible liquids, not yet emulsified
B. An emulsion of Phase II dispersed in Phase I
C. The unstable emulsion progressively separates
D. The surfactant (purple outline around particles) positions itself on the interfaces between Phase II and Phase I, stabilizing the emulsion

 

 We can prescribe seminal emulsions by two ways: large-scaled and reduced.

               Rp.: Seminis Amygdali dulcis 18,0

                       Aquae destillatae ad 180 ml

                       M.f. emulsum

                       D.S. In 1 table spoon three times a day

        Or:

               Rp.: Emulsi seminum Amygdali dulcis 180,0

                       D.S. Take in 1 table spoon three times a day.

(seminum – genitive case plural from semen, seminis – genitive case singular from semen).

Amygdali dulcis

 

Preparing oil emulsions it is necessary to take not only the corresponding oil and distilled water, but some emulsifying agents, which provide the stable state of the fat drops in the water thickness for a long time. The wide using emulsifiers are Gelatosa, Arabian gum (Gummi Arabicum), apricot gum (Gummi Armeniacae), chicken egg yolk (Vitellum ovi) and others. Usually on every 2 parts of oil 1 part of the emulsifier and 17 parts of water are taken (correlation 2: 1: 17). The yolk of the one egg is used for preparing emulsion that includes oil 15 g (emulsion volume is 150 ml), but 3 g Apricot gum – for 10 g of the oil (for 100 ml emulsion).

Emulsion stability refers to the ability of an emulsion to resist change in its properties over time.There are four types of instability in emulsions: flocculation, creaming, coalescence and Ostwald ripening. Flocculation occurs when there is an attractive force between the droplets, so they form flocs, like bunches of grapes. Coalescence occurs when droplets bump into each other and combine to form a larger droplet, so the average droplet size increases over time. Emulsions can also undergo creaming, where the droplets rise to the top of the emulsion under the influence of buoyancy, or under the influence of the centripetal force induced when a centrifuge is used.

An appropriate "surface active agent" (or "surfactant") can increase the kinetic stability of an emulsion so that the size of the droplets does not change significantly with time. It is then said to be stable.

Oil emulsions are prescribed also by developed and reduced ways. Prescribing emulsion by large-scale method we recalculate all components (oil, water and emulsifier) with their quantity according to correlation after word Rp. Then write down M.F. emulsum. D.S. and the way of application.

                      Rp.: Olei Amygdalarum 10 ml

                              Gummi Arabici 5,0

                              Aquae destillatae 85 ml (or: ad 100 ml)

                              M.f. emulsum

                              D.S. Take inside in one dessert-spoon

                                       three times a day.

  Using reduced way of prescription it is necessary to indicate the oil name, its quantity and common emulsion quantity after medical form name (Emulsi)

                     Rp.: Emulsi olei Lini ex 10ml -100ml

                             D.S. In 1 tea-spoon three times a day.

  In cases when quantity of the oil is not noted in the prescription, from 10 oil parts must be prepared 100 parts of emulsion. For example, for preparing 200 ml of emulsion it is necessary to take oil 20 g, Gelatosae – 10 g and 170 ml of  water.

 

Suspensions

  Suspensions (Suspensio – nominative case, singular, suspensionis – genitive case, singular) – are the liquid medical forms, two-phase system, which contains disperse phase formed by particles of unsoluble in the water medical agents (powders) and disperse medium represented by water, oils, glycerin or other fluids. This medicinal form is intended for external, internal and parenteral applications.

  The prescriptions for magistral suspensions are written out by developed or reduced ways, but for officinal suspensions – only by reduced way.

                      Rp.: Oxytetracyclini 1,0

                              Olei Olivarum ad 100,0

                              M.f. suspensio

                              D.S. In 1 tea-spoon three times a day.

 

                      Rp.: Suspensionis Hydrocortisoni 2,5 % 5 ml

                              D.t.d. N.5

                              S. Inject into the muscle by 5 ml (before injecting

                                  shake the content).

 

Tinctures

  Tinctures – Tincturae (tinctura – nominative singular, tincturae – genitive singular) – are represented by (spirituous) alcoholic, hydroalcoholic, alcohol-ether liquid extracts from plant raw material. There are three methods of preparing tinctures, such as maceration (drawing), percolation (pressing) or dissolving of the dry extracts. All tinctures are officinal. It means that their concentration is detected by Pharmacopeia. And they are manufacturing on the pharmaceutical factiries. They are stable and can be keeping for a long time. Prescribing such forms it is not necessary to indicate number of the plant parts, tincture concentration in the prescription because they are officinal.

Valerian

 

Prescription has such form: medicinal form name – Tincturae, then the name of plant and tincture quantity are noted. Those forms are dosed by drops – from 5 to 30 drops for one reception depending on the action intensity. Accordingly we write out the common quantity in ml (5-30 ml).

                       Rp.: T-rae Valerianae 20 ml

                               D.S. In 20 drops three times a day.

  The equal parts of tinctures are taken (if they have equal therapeutic dosage) if we prescribed combination of them (complex tinctures).

                       Rp.: T-rae Valerianae

                               T-rae Convallariae ana 10 ml

                               M.D.S. In 20 drops twice a day.

  In cases when the doses of the mixed tinctures are different, then one of them is taken in quantity that is less than quantity of the second in the number of times in which it’s one time dose is less than the second one’s.

 

 It is necessary to prescribe mixture of the strophanthus tincture (T-ra Strophanthi), single dose is 5 drops, and valerian tincture (T-ra Valerianae), single dose is 15 drops.

                       Rp.: T-rae Strophanthi 5 ml

                               T-rae Valerianae 15 ml

                               M.D.S. In 20 drops three times a day.

  Tinctures may be included to the mixtures with other medicinal compounds.

 

Extracts

Chamomilla

 

  Liquid extracts (Extracta fluida) are the concentrated drawing usually obtained from medicinal plant raw material. Extraction substances are water, ethyl alcohol, hydroalcoholic solutions. All liquid extracts are officinal forms. They are written out and prescribed the same way as the tinctures.

                        Rp.: Extr. Viburni fluidi 30 ml

                                D.S. In 30 drops twice a day.

  By definitions extracts besides liquid are dry (Extra sicca) and dense (thick) (Extracta spissa). Dry and dense extracts are prescribed and produced in powders, tablets, suppositories and in other medicinal forms.

 

 

New Galen medicines

  New Galen medicines, these are aqueous, hydro-alcoholic and chloroform-alcoholic and other extracts from plant raw material. They are distinguished from Galen medicines by maximal purity from ballast substances and by bigger pharmacologic activity. They are officinal forms and are prescribed like tinctures, by the same way:

                        Rp.: Adonisidi 15 ml

                                D.S. In 15 drops three times a day.

 

Oils — oils of plants and fats of animal reserve tissues consist­ing of fat acid glycerids. Oils: liquid fats (oils) — non-drying (peanut, cas­tor), semi-drying (sunflower, corn), drying (heropseed, linseed) are obtained by pressing seeds and plant fruits. Animal fats - liquid fats (fats of land animals, sea animals, fishes), as well as hard fats. They are used as excipients in pharmaceutical production, and as individual medicinal prod­ucts. Oils are classified as oils for peroral and external application.

 

Mixtures

  Mixtures (Mixturae) – liquid medical form consisting of the solvent (water, aromatic distilled water, alcohol, infusions, decoction, emulsions, tinctures, glycerin, etc) and two or more solid medical agents dissolved in or received by the way of mixing some liquids.

  If mixture contains tincture, decoction, emulsion it is necessary to write down their name on the first place.

  Aqua Menthae piperitae, aqua Foeniculi, aqua Amygdalarum amararum, aqua Rosae and others are the basic aromatic waters, which are used for preparing mixtures. Aromatic waters, contained to the composition of the mixture, are not the solvents but also they improved medicine taste, smell and some times had additional qualities too. For example, aqua Menthae piperitae impairs fermentation process in the intestinal tract; aqua Amygdalarum amararum partially removes the gastric pain.

  For improving taste and smell of the mixtures we admix other substances with corrigent action (corrigens). Mainly these substances are represented by syrups (10-30% of the common mixture volume), for example:

Sirupus simplex – sugar syrup,

Sirupus Citri unshiu - peel mandarin syrup,

Sirupus Rubi idaei – raspberries syrup,

Sirupus Cerasi – cherry syrup,

Sirupus Rhei, Sirupus Glycyrrhizae – lignorice root syrup.

  In case, when the mixture contains substances with expressed irritative action it is necessary to add to the mixture instead of the solvent part mucus (30-60 % of the common mixture volume): mucilago Salep – mucus Salep, muc. Gummi arabici – Arabian gum mucus, muc. Amyli (Solani, Majydis, Oryzae, Tritici) – Starch (potatoes, maize, rice, wheaten) mucuses. Mucus is included into the mixture also when unsolvable substances are precente there too. In fact, the role of mucuses is that they are promoted forming suspension from these unsolvable substances. These mixtures must be mixed before taking what is indicated in the signature.

  Mixture is dosed by spoons when its liquid phase was represented by water, aromatic water, decoction, infusion, emulsion. If tinctures or liquid extracts are the liquid mixture phase it must be dosed by drops.

  Glycyrrhiza glabra

 

  Mixtures are convenient for prescribing to the hard sick patients, children, old people for internal and external using. Solved in mixtures medicinal substances are better adsorbed and act more quickly in comparison to the powders and tablets. But mixtures have such defect qualities as: they are not accurate in dosage, not portative and not stable (written out only for 3-4 days).

  Syrups — a liquid pharmaceutical form, presenting a mixture of medicinal product with concentrated solution of sugar or any other sweet­ener. Added to the content of syrups are excipients, which carry out dif­ferent functions, as well as dyes, flavors, and alcohol or other preserva­tives are added in syrups to prevent fermentation.

Syrups are intended for peroral application. In that case, when a phar­maceutical form is intended only for one method of use, route of adminis­tration «for peroral use» can be omitted.

Syrups can be produced in single-dose and multy-dose containers.

For prescribing mixture all calculation we must base on the single dose and common number of reception. For example, it is necessary to write out tincture for 4 days, dosed in 1 table-spoon 3 times a day. This mixture will contain sodium bromide (Natrii bromidi) single dose – 0,3 gr., codeine phosphate (Codeini phosphas) single dose 0,015 gr.

  Calculation:

               number of reception 3 x 4 = 12;

               Natrii bromidi 0,3 g x 12 = 3,6 g;

               Codeini phosphatis 0,015 g x 12 = 0,18 g;

  Water is used as solvent, if there was no other notes.

               solvent quantity: 15 ml x 12 = 180 ml;

  Prescription will look like this:

              

    Rp.: Codeini phosphatus 0,18

                       Natrii bromidi 3,6

                       Aquae destillatae ad 180 ml

                       M.D.S. In 1 table-spoon three times a day.

  Prescribe mixture, including chloral hydrate, single close – 1,0 g, and mucus Salep. Prescribe for 2 curative enemas.

               Rp.: Chlorali hydratis 2,0

                       Mucilaginis Salep 40,0

                       Aquae destillatae ad 100,0

                       M.D.S. For 2 curative enemas.

  Prescribe mixture (for 4 days) that contains infusion Thermopsis herb, sodium benzoate (pro dosi 0,05 g) and Lignorice root syrup. Use – 1 table-spoon three times a day.

               Rp.: Infusi herbae Thermopsidis ex 0,45-180,0

                       Natrii benzoatis 0,6

                       Sirupi Glycyrrhizae 18,0

                       M.D.S. In 1 table-spoon three times a day.

 

Thermopsis lanceolata

 

 For this prescription we take 10 % syrup from mixture common quantity. That’s why we cannot take it to account (because dosage by table-spoons isn’t so punctual) and take away 18 ml of the mixture contain. But if we take syrup in quantity 54 ml (30 %), it must be taken to calculation. 

 

Medical forms for injections

  To the medical forms, which are intended for injections, belong: sterilized water and solutions, suspensions, emulsions and also powders, and tablets, which are dissolved in the appropriate dissolvent before injecting. They are mainly used for hypodermic (subcutaneous), intramuscular, intravenous and intra-arterial injections.

  As against solutions for external use, the solutions for injections are prepared on water for injections (bidistilled, sterilized, apirogenic water – it does not cause the increase of body temperature at parenteral injection). The medical forms for injections demand: sterility, absence of mechanical impurity, stability, apirogenity and in some of cases – isotonicity.

  The medicines for injections, which are produced in ampoules and bottles by a pharmaceutical industry, are already sterilized, in a drugstore they are not sterilized, drugstore only sales them.

There are several methods of injection or infusion used in humans, including intradermal, subcutaneous, intramuscular, intravenous, intraosseous, intraperitoneal, intrathecal, epidural, intracardiac, intraarticular, intracavernous, and intravitreal. Rodents used for research are often administered intracerebral and intracerebroventricular injections as well. Long-acting forms of subcutaneous/intramuscular injections are available for various drugs, and are called depot injections.

A graphic representation of the interface between skin epithelium and the underlying connective tissue. Zone B, indicating the region of overlapping projections of epithelium and connective tissue, is the papillary dermis. Zone C, indicating the region of dermis that lies immediately subjacent to the interdigitations of epithelium, is the reticular dermis.

      

Injections are among the most common health care procedures, with at least 16 billion administered in developing and transitional countries each year. 95% of injections are administered in curative care, 3% are for immunization, and the rest for other purposes, such as blood transfusions.

The solutions for injections, which are prepared in a drugstore, are the subject to on obligatory sterilization. In the prescriptions it is noted by a word “Sterilisetur” (“Da sterilis”, “Pro injectionibus”).

  The solutions for injections in ampoules are prescribed out by the reduced way. After a word Rp.: the medical form Solutionis… is specified, name of a medicine, its concentration in percentage and its quantity. After that D.t.d.N… in ampullis, and signatura S.

                  Rp.: Solutionis Glucosi 40 % 50 ml

                         D.t.d.N. 10 in ampullis

                         S. For intravenous injection 50 ml.

  Prescribing a dry substance in ampoules the name of the substance is specified and its quantity in one ampoule. Then D.t.d.N… in ampullis, and signatura S. The order of dissolution of substances, the way of introduction, periodicity of injections are specified in signatura.

                  Rp.: Vincristini 0,005

                          D.t.d.N. 6 in ampullis

                          S. To dissolve contents of ampoule in 5 ml of isotonic sterilized

                          solution of Sodium chloride. To inject intravenously 1 time a

      week.

  Besides, in ampoules new Galen preparations, preparations of organs and tissues, officinal solutions are prescribed out. In these cases after a word Rp.: specify only the name of the preparation and its quantity D.t.d.N…. in ampullis and signatura.

                   Rp.: Digalen – neo 1 ml

                           D.t.d.N. 10 in ampullis

                           S. Infuse hypodermic 1 ml 1 time a day.

 

                   Rp.: Pituitrini pro injectionibus 1 ml (5 U)

                           D.t.d.N. 6 in ampullis

                           S. Infuse hypodermic 1 ml 1 time a day.

  Some medicines for injections are prescribed in bottles. Prescribing medicines in bottles adhere to those rules, as those of prescribing in ampoules.

 The only difference is that after D.t.d.N… we don’t make any designations. If we prescribe a preparation in bottles of dark glass, we write D.t.d.N… in vitro nigro.

                    Rp.: Ampicillini 0,5

                            D.t.d.N. 10

                            S. To dissolve the content of the bottle in 2 ml 0,5  % of a solution

                            of  Novocainum. Inject intramuscular 4 times a day.

 

                      Rp.: Suspensionis Hydrocortisoni acetatis 2,5 % 5 ml

                              D.t.d.N. 6

                              S. Inject 5 ml intramuscular 1 time a day.

  In some cases the name of the ready medical forms for injections, according to Pharmacopoeia, includes the words “pro injectionibus”, for example, Corticotropium pro injectionibus, Parathyreoidinum pro injectionibus. It doesn’t mean, that these medicines are sterilized in a drugstore; they are already sterilized and are selling in a ready state.

                       Rp.: Corticotropini pro injectionibus 30 U

                               D.t.d.N. 5

                               S. To dilute the content of the bottle in 3 ml of the water for

                               injections. Inject intramuscular 1 time a day.

If we prescribe a preparation, activity of which is indicated in units, it is necessary to mark them in the prescription. For example, it is necessary to prescribe out 6 bottles of Insulin 5 ml each, with activity 40 U in 1 ml.

                       Rp.: Insulini pro injectionibus 5 ml (40 U – 1 ml)

                               D.t.d.N. 6

                               S. 0,5 ml under skin 2 times a day.

 

                        Rp.: Insulini pro injectionibus 5 ml (200 U)

                                D.t.d.N. 6

                                S. 0,5 ml under skin 2 times a day.

  Discharging of the prescriptions on solutions for injections, which are prepared in a drugstore, their sterility is necessarily indicated. If medicines contain several components, after their recalculation  write M. Sterilisetur. Then  D.S. and Signatura.

                         Rp.: Sol. Natrii nucleinatis 2 % 25 ml

                                Sterilisetur!

                                D.S. Inject intramuscular 5 ml 1 time a day.

 

                       Or:  Rp.: Natrii nucleinatis pro injectionibus 2 % 25 ml

                                      D.S. Inject into muscle on 5 ml 1 time a day.

 

                        Or: Rp.: Sol. Natrii nucleinatis 2% 25 ml

                                      Da sterilis!

                                      S. Inject into muscle on 5 ml 1 time a day.

 

                         Or: Rp.: Natrii nucleinatis 0,5

                                      Aquae pro injectionibus ad 25 ml.

                                      Misce. Sterilisetur!

                                      D.S. Inject intramuscular 5 ml 1 time a day.

  If structure of the medicine form for parenteral introduction includes substances, which are easily destroyed at sterilization, for example solution of epinephrine (Adrenalinum), then they are added aseptically after sterilization of the basic solution. Thus we write Adde aseptice in the prescription:

                          Rp.: Novocaini 1,25

                                  Sol. Natrii chloridi isotonicae 0,9 % ad 500 ml

                                  M. Sterilisetur!

                                  Adde aseptice Sol. Adrenalini hydrochl. 0,1 % gtts. XXV

                                  D.S. For infiltrative anesthesia.

 

Suspensions — the liquid pharmaceutical form, which contains as a disperse phase one or more active substances dissolved or dispersed in the appropriate solvent. Suspensions contain excipients intended for maintenance of necessary viscosity, pH maintenance or stabilization, for improvement of solubility of active substances, flavorings, flavor addi­tives, etc.

Most common are suspensions, in which the dispersion medium is a water, extracts of pharmaceutical plants, glycerin, and oils as a disperse phase- various powder-like substances. These are thermodynamically unstable systems, muddy, opaque, characterized by kinetic (sedimenta­tion) and aggregate (condensation) instability. Presence of precipitate, which easy disperses with formation of suspension, is allowed.

Suspensions are intended for external, internal, parenteral application, etc. Suspensions can be classified by dispersion medium (water, oil), by size of particles.

Suspensions can be for external application (for treating skin surface etc.), for peroral application, for lavage and as lotions nasal, eye, ear, den­tal, suspensions, rectal and vaginal suspensions are applied.

Suspensions for injections are used for parenteral administration, sus­pensions for inhalations and intratracheal administration are wid espread, the size of their particles being much smaller.

Suspensions are manufactured as single-dose and multi-dose containers.

Containers of suspensions for rectal, vaginal, ear application are adapt­ed to administer a medicinal product in rectum, vagina, etc. or have an appropriate applicator.

 

Shampoos — liquid pharmaceutical form, consisting of a sol­vent (water, extracts of plant raw material, alcohol, glycerin, etc.), soluble alkaline salts of absolute fatty acids, and biologically active substances dissolved in or mixed with it.

Shampoos are intended for external application (for treatment of skin of a head, hair illnesses).

Pharmaceutically produced liquid medicines can either be called liquids, solutions, syrups or mixtures. Liquid medicines are largely designed for patients who are unable to swallow tablets or capsules and therefore are prescribed mainly for children and the elderly and are designed to ensure that the drug is dispersed evenly throughout, the taste of the drug is masked by sweeteners and flavourings and a usual dose is given in 5ml which is a sensible amount to swallow.  The consistency is also considered by manufacturers as gloopy liquids are easier to manage and are less likely to be aspirated.

Figure 1 Diagrammatic representation of a liquid.

Water is the most commonly used solvent however due to drug Instability in water some liquid medicines contain stabilizers.  Occasionally alternative liquid solvents such as glycerol or alcohol are used.  Where the drug doesn't dissolve in the liquid solvent manufacturers use suspending agents to ensure the even drug distribution.  Figure four provides a diagrammatic representation of what may be found in a liquid medicine.  It can be seen that these are not simple formulations and considerably more complex than a crushed tablet in water.

Sterilization

Sterilization is necessary for the complete destruction or removal of all microorganisms (including spore-forming and non-spore-forming bacteria, viruses, fungi, and protozoa) that could contaminate pharmaceuticals or other materials and thereby constitute a health hazard. Since the achievement of the absolute state of sterility cannot be demonstrated, the sterility of a pharmaceutical preparation can be defined only in terms of probability. The efficacy of any sterilization process will depend on the nature of the product, the extent and type of any contamination, and the conditions under which the final product has been prepared. The requirements for Good Manufacturing Practice should be observed throughout all stages of manufacture and sterilization.

Classical sterilization techniques using saturated steam under pressure or hot air are the most reliable and should be used whenever possible. Other sterilization methods include filtration, ionizing radiation (gamma and electron-beam radiation), and gas (ethylene oxide, formaldehyde).

For products that cannot be sterilized in the final containers, aseptic processing is necessary. Materials and products that have been sterilized by one of the above processes are transferred to presterilized containers and sealed, both operations being carried out under controlled aseptic conditions.

Whatever method of sterilization is chosen, the procedure must be validated for each type of product or material, both with respect to the assurance of sterility and to ensure that no adverse change has taken place within the product. Failure to follow precisely a defined, validated process could result in a non-sterile or deteriorated product. A typical validation programme for steam or dry-heat sterilization requires the correlation of temperature measurements, made with sensory devices to demonstrate heat penetration and heat distribution, with the destruction of biological indicators, i.e. preparations of specific microorganisms known to have high resistance to the particular sterilization process. Biological indicators are also used to validate other sterilization methods (see specific methods), and sometimes for routine control of individual cycles. Periodic revalidation is recommended.

 

Heating in an autoclave (steam sterilization)

 

Exposure of microorganisms to saturated steam under pressure in an autoclave achieves their destruction by the irreversible denaturation of enzymes and structural proteins. The temperature at which denaturation occurs varies inversely with the amount of water present. Sterilization in saturated steam thus requires precise control of time, temperature, and pressure. As displacement of the air by steam is unlikely to be readily achieved, the air should be evacuated from the autoclave before admission of steam. This method should be used whenever possible for aqueous preparations and for surgical dressings and medical devices.

The recommendations for sterilization in an autoclave are 15 minutes at 121-124 °C (200 kPa).¹ The temperature should be used to control and monitor the process; the pressure is mainly used to obtain the required steam temperature. Alternative conditions, with different combinations of time and temperature, are given below.

¹ 1 atm = 101 325 Pa

 

 

Minimum sterilization time should be measured from the moment when all the materials to be sterilized have reached the required temperature throughout. Monitoring the physical conditions within the autoclave during sterilization is essential. To provide the required information, temperature-monitoring probes should be inserted into representative containers, with additional probes placed in the load at the potentially coolest parts of the loaded chamber (as established in the course of the validation programme). The conditions should be within ±2 °C and ±10 kPa (±0.1 atm) of the required values. Each cycle should be recorded on a time-temperature chart or by other suitable means.

 

Aqueous solutions in glass containers usually reach thermal equilibrium within 10 minutes for volumes up to 100 ml and 20 minutes for volumes up to 1000 ml.

 

Porous loads, such as surgical dressings and related products, should be processed in an apparatus that ensures steam penetration. Most dressings are adequately sterilized by maintaining them at a temperature of 134 - 138 °C for 5 minutes.

In certain cases, glass, porcelain, or metal articles are sterilized at 121 - 124 °C for 20 minutes.

 

Fats and oils may be sterilized at 121 °C for 2 hours but, whenever possible, should be sterilized by dry heat.

In certain cases (e.g. thermolabile substances), sterilization may be carried out at temperatures below 121 °C, provided that the chosen combination of time and temperature has been validated. Lower temperatures offer a different level of sterilization; if this is evaluated in combination with the known microbial burden of the material before sterilization, the lower temperatures may be satisfactory. Specific conditions of temperature and time for certain preparations are stated in individual monographs.

The bioindicator strain proposed for validation of this sterilization process is: spores of Bacillus stearothermophilus (e.g. ATCC 7953 or CIP 52.81) for which the D-value (i.e. 90% reduction of the microbial population) is 1.5-2 minutes at 121 °C, using about 10⁶ spores per indicator.

 

Dry-heat sterilization

 

In dry-heat processes, the primary lethal process is considered to be oxidation of cell constituents. Dry-heat sterilization requires a higher temperature than moist heat and a longer exposure time. The method is, therefore, more convenient for heat-stable, non-aqueous materials that cannot be sterilized by steam because of its deleterious effects or failure to penetrate. Such materials include glassware, powders, oils, and some oil-based injectables.

Preparations to be sterilized by dry heat are filled in units that are either sealed or temporarily closed for sterilization. The entire content of each container is maintained in the oven for the time and at the temperature given in the table below. Other conditions may be necessary for different preparations to ensure the effective elimination of all undesirable microorganisms.

 

 

Specific conditions of temperature and time for certain preparations are stated in individual monographs.

The oven should normally be equipped with a forced air system to ensure even distribution of heat throughout all the materials processed. This should be controlled by monitoring the temperature. Containers that have been temporarily closed during the sterilization procedure are sealed after sterilization using aseptic techniques to prevent microbial recontamination.

The bioindicator strain proposed for validation of the sterilization process is: spores of Bacillus subtilis (e.g. var. niger ATCC 9372 or CIP 77.18) for which the D-value is 5-10 minutes at 160 °C using about 10⁶ spores per indicator.

 

Filtration

 

Sterilization by filtration is employed mainly for thermolabile solutions. These may be sterilized by passage through sterile bacteria-retaining filters, e.g. membrane filters (cellulose derivatives, etc.), plastic, porous ceramic, or suitable sintered glass filters, or combinations of these. Asbestos-containing filters should not be used.

Appropriate measures should be taken to avoid loss of solute by adsorption onto the filter and to prevent the release of contaminants from the filter. Suitable filters will prevent the passage of microorganisms, but the filtration must be followed by an aseptic transfer of the sterilized solution to the final containers which are then immediately sealed with great care to exclude any recontamination.

Usually, membranes of not greater than 0.22 μm nominal pore size should be used. The effectiveness of the filtration method must be validated if larger pore sizes are employed.

To confirm the integrity of filters, both before and after filtration, a bubble point or similar test should be used, in accordance with the filter manufacturer's instructions. This test employs a prescribed pressure to force air bubbles through the intact membrane previously wetted with the product, with water, or with a hydrocarbon liquid.

All filters, tubes, and equipment used "downstream" must be sterile. Filters capable of withstanding heat may be sterilized in the assembly before use by autoclaving at 121 °C for 15 - 45 minutes depending on the size of the filter assembly. The effectiveness of this sterilization should be validated. For filtration of a liquid in which microbial growth is possible, the same filter should not be used for procedures lasting longer than one working day.

 

Exposure to ionizing radiation

 

Sterilization of certain active ingredients, drug products, and medical devices in their final container or package may be achieved by exposure to ionizing radiation in the form of gamma radiation from a suitable radioisotopic source such as ⁶⁰Co (cobalt 60) or of electrons energized by a suitable electron accelerator. Laws and regulations for protection against radiation must be respected.

Gamma radiation and electron beams are used to effect ionization of the molecules in organisms. Mutations are thus formed in the DNA and these reactions alter replication. These processes are very dangerous and only well-trained and experienced staff should decide upon the desirability of their use and should ensure monitoring of the processes. Specially designed and purpose-built installations and equipment must be used.

It is usual to select an absorbed radiation level of 25 kGy¹ (2.5 Mrad)², although other levels may be employed provided that they have been validated.

¹ kilogray

² megarad

Radiation doses should be monitored with specific dosimeters during the entire process. Dosimeters should be calibrated against a standard source on receipt from the supplier and at appropriate intervals thereafter. The radiation system should be reviewed and validated whenever the source material is changed and, in any case, at least once a year.

The bioindicator strains proposed for validation of this sterilization process are: spores of Bacillus pumilus (e.g. ATCC 27142 or CIP 77.25) with 25 kGy (2.5 Mrad) for which the D-value is about 3 kGy (0.3 Mrad) using 10⁷-10⁸ spores per indicator; for higher doses, spores of Bacillus cereus (e.g. SSI C 1/1) or Bacillus sphaericus (e.g. SSl C₁A) are used.

 

Gas sterilization

 

The active agent of the gas sterilization process can be ethylene oxide or another highly volatile substance. The highly flammable and potentially explosive nature of such agents is a disadvantage unless they are mixed with suitable inert gases to reduce their highly toxic properties and the possibility of toxic residues remaining in treated materials. The whole process is difficult to control and should only be considered if no other sterilization procedure can be used. It must only be carried out under the supervision of highly skilled staff.

The sterilizing efficiency of ethylene oxide depends on the concentration of the gas, the humidity, the time of exposure, the temperature, and the nature of the load. In particular, it is necessary to ensure that the nature of the packaging is such that the gas exchange can take place. It is also important to maintain sufficient humidity during sterilization. Records of gas concentration and of temperature and humidity should be made for each cycle. Appropriate sterilization conditions must be determined experimentally for each type of load.

After sterilization, time should be allowed for the elimination of residual sterilizing agents and other volatile residues, which should be confirmed by specific tests.

Because of the difficulty of controlling the process, efficiency must be monitored each time using the proposed bioindicator strains: spores of Bacillus subtilis (e.g. var. niger ATCC 9372 or CIP 77.18) or of Bacillus stearothermophilus, (e.g. ATCC 7953 or CIP 52.81). The same quantity of spores should be used as for "Heating in an autoclave" and "Dry-heat sterilization".

 

 

LIQUID MEDICATION ADMINISTRATION

If the medicine comes in suspension form, shake well before using.

Do not use silverware spoons for giving medication. They are not all the same size. A silverware teaspoon could be as small as a half teaspoon or as large as 2 teaspoons.

Measuring spoons used for cooking are accurate, but they spill easily.

 

Oral syringes have some advantages for giving liquid medications.

• They are accurate.

• They are easy to use.

• You can take a capped syringe containing a dose of medication to your child's daycare or school.

There can be problems with oral syringes, however. The FDA has had reports of young children choking on syringe caps. To be safe, remove the cap before you use an oral syringe. Throw it away if you do not need it for future use. If you need it, keep it out of reach of infants and small children.

Dosing cups are also a handy way to give liquid medications. However, dosing errors have occurred with them. Always check to make sure the units (teaspoon, tablespoon, mL, or cc) on the cup or syringe match the units of the dose you want to give.

Liquid medications often don't taste good, but many flavors are now available and can be added to any liquid medication. Ask your pharmacist.

Unit conversions

• 1 mL = 1 cc

• 2.5 mL = 1/2 teaspoon

• 5 mL = 1 teaspoon

• 15 mL = 1 tablespoon

• 3 teaspoons = 1 tablespoon

 

Pen injection device (for Humatrope)

Preparing Your New Cartridge

Remove ALL contents from the tray.
Note: This product is designed for left or right handed use so you may use whichever hand is most comfortable for you.

Grasp the gray Needle Cover, at the bottom of the Diluent Syringe.

Remove the Needle Cover and discard. DO NOT depress the Plunger yet. It is okay if a drop of fluid is lost. It is not necessary to release air from the Diluent Syringe.

Hold the cartridge, with the Black Triangles toward the Diluent Syringe. Align the cartridge and Diluent Syringe in a straight line. DO NOT insert the cartridge at an angle.

PUSH the cartridge STRAIGHT in until it stops AND the Black Triangles ARE COVERED. You may hear or feel a click. DO NOT twist the cartridge.

Hold the Diluent Syringe and the cartridge together with TWO HANDS. Push and release the Plunger 2 or 3 times until the Diluent is in the cartridge.

Remove your thumb from the Plunger and check that the Diluent Syringe is empty [it is normal for small drops of Diluent to remain in the Diluent Syringe].

With your thumb OFF the Plunger, pull the cartridge away from the Diluent Syringe.

Place the End Cap on a hard, flat surface. Push the Diluent Syringe onto the End Cap and immediately discard the Diluent Syringe as instructed by your healthcare professional.

Mix the cartridge by gently inverting 10 times and let it sit for 3 minutes, DO NOT SHAKE.

Inspect the solution.

 

Unit Conversion

Mass:

• mcg → mg → g → kg    ( ÷ by 1,000 )

• mcg ← mg ← g ← kg    ( x by 1,000 )

• lb → kg    ( ÷ by 2.2 )

• lb ← kg    ( x by 2.2 )

Volume:

• mcL → mL → L → kL    ( ÷ by 1,000 )

• mcL ← mL ← L ← kL    ( x by 1,000 )

Time:

• min → hr    ( ÷ by 60 )

• min ← hr    ( x by 60 )

Example: Convert 5,000 mcg to mg.

• mcg → mg → g → kg    ( ÷ by 1,000 )

• 5,000 mcg ÷ 1,000 = 5 mg

Example: Convert 44 lb to kg.

• lb → kg    ( ÷ by 2.2 )

• 44 lb ÷ 2.2 = 20 kg

Example: Convert 0.003 L to mcL.

• mcL ← mL ← L ← kL    ( x by 1,000 )

• 0.003 L x 1,000 = 3 mL

• 3 mL x 1,000 = 3,000 mcL

Example: Convert 5 hours to minutes.

• min ← hr    ( x by 60 )

• 5 hr x 60 = 300 min

Parenteral Medications

Routes of Administering Parenteral Medications

Parenteral medications are any medications given by injection. Injection is usually given in one of three different ways:

• Subcutaneously (subQ): A subcutaneous injection is one that is given in the fatty layer of tissue under the skin. The maximum amount of fluid an adult can safely be given subcutaneously is 1 mL. (Sometimes you may see this abbreviated as s.c., SC, s.q., or SQ, but you should never abbreviate it this way, since these outdated abbreviations have often been misread.)

• Intramuscularly (IM): An intramuscular injection is one that is given in the muscle. The maximum amount of fluid an adult can safely be given intramuscularly is 3 mL; for a child, the maximum is 1 mL.

• Intravenously (IV): An intravenous injection is one that is given directly into the vein. Much higher amounts of fluids can be given intravenouly; in fact, the limit on the amount of fluid that can be given intravenously is generally only capped by the limit on the amount of fluid a patient can take in each day (for a healthy patient this range is usually 35-50 mL/kg body weight/day, but this amount can vary greatly depending upon the condition of the patient).

Note the abbreviations for subcutaneously, intramuscularly, and intravenously: subQ, IM, and IV, respectively. We will wait until later lectures to learn in depth about IV medication; for the moment, we will give subQ, IM, and IV medications using syringes only.

Types of Syringes Used for Parenteral Medication

There are several different sizes of syringes that might be used for medication. You should always use the smallest possible syringe in which the dosage will fit, because the smaller the syringe, the more accurately you can measure the dosage:

• 3 mL syringe (3 cc syringe) : This is the most commonly used syringe. As it's name suggests, it holds a total of 3 mL of fluid. Every tenth of a mL is marked on the syringe, and every half mL is labeled; this means that any dosage we plan to measure using a 3 mL syringe should be rounded to the nearest tenth.

Dosages between 1-3 mL should always be measured in a 3 mL syringe.

Some 3 mL syringes have the mL scale to the right and a minim scale to the left; be careful not to measure mL on the minim scale, as this will result in an incorrect dosage! 

• Tuberculin syringe: A tuberculin syringe is used to measure small doses, so it is often used to dose small children and infants. There are two different sizes of tuberculin syringes which you might encounter: one kind can hold a total of 1 mL, and another kind can hold a total of 0.5 mL; every hundredth of a mL is marked on a tuberculin syringe, and every fifth of a mL is labeled; this means that any dose we plan to administer with a tuberculin syringe should be rounded to the nearest hundredth.

Any dose smaller than 0.5 mL should be measured using a tuberculin syringe, and any dose less than 1 mL can be more accurately measured using a tuberculin syringe, if a tuberculin syringe which holds 1 mL is available. Because a tuberculin syringe has every hundredth of a mL marked whereas the 3 mL syringe has only every tenth of a mL marked, it is possible to measure doses with more accuracy in a tuberculin syringe.

• 5-12 mL syringes: When an IV dose requires a syringe that can hold more than 3 mL, a 5, 6, 10, or 12 mL syringe can be used. On each of these size syringes, every 0.2, or two tenths, is marked, so be very careful not to misread a mark as one tenth of a mL !

Dosages between 3-12 mL should be measured using one of these syringes; always choose the smallest possible syringe in which the dose will fit to ensure the highest level of accuracy.

• 20 mL (or more) syringes: Occasionally it is necessary to use even larger syringes to measure IV fluids. In this case there are syringes that can measure a maximum of 20 mL or more; these syringes only have every mL marked.

Any dosage above 12 mL must be measured using a 20 mL syringe or larger.

20 mL syringe syringe

• Tubex and Carpuject cartridges: These are special pre-filled cartridges produced by two specific companies that can be dropped into a plastic injector with a plunger for injection. The ones we will encounter in this class will have markings every tenth of a mL and will contain up to 2.5 mL of fluid.

Measuring Dosages in a Syringe

To measure a dosage in a syringe, we must line up the top of the black rubber plunger exactly with the line that marks the dosage we want to administer.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the third mark past the 2. Since this is a 3 mL syringe and has everytenth of a mL marked, that means that we are three tenths past 2, which is a total of 2.3 mL.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the first mark past the 1/2 which follows the 2. Since this is a 3 mL syringe and has every tenth of a mL marked, that means that we are one tenth past 2.5, which is a total of 2.6 mL.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the third mark past the 4. Since this is a 6 mL syringe and has every0.2 mL marked, that means that we are three 0.2s past 4, which is a total of 4.6 mL.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the second mark past the 10. Since this is a 12 mL syringe and has every 0.2 mL marked, that means that we are two 0.2s past 10, which is a total of 10.4 mL.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the second mark past the 10. Since this is a 20 mL syringe and has every whole mL marked, that means that we are two whole mL past 10, which is a total of 12 mL.

Example:

If we look closely, we can see that this syringe has the top of the black rubber stopper lined up with the third mark past the .60. Since this is a tuerculin syringe and has every hundredth of a mL marked, that means that we are three hundredths of a mL past 0.6, which is a total of 0.63 mL.

Reading Medication Labels and Calculating Dosages

Reading Medication Labels

Before we can even begin to calculate how much medicine to give a patient, we must be able to read a medication label correctly. There are several important pieces of information we should look for whenever we look at a medication label:

1.     Name of the medication
There are actually at least two names on every medication label:

o    The trade name is the name assigned to the drug by the manufacturer and it varies from one company to another. A single drug may have many different trade names if it is manufactured and sold by many different companies. The trade name of a drug is usually capitalized. 
For example, you may be familiar with the over-the-counter pain relievers Advil and Motrin. These are actually two different brand names for the same drug that is manufactured by two different companies.

o    The generic name is the name assigned to the drug officially in the United States. There is only one generic name for each drug, and all drug labels must list the drug's generic name in addition to any trade names so that the drug can be identified by its offical name. The generic name of a drug is generally written in lower case letters. 
So, Motrin and Advil are trade names that each refer to the same drug, and its offical generic name is ibuprofen. If you look closely at a bottle of Advil or Motrin, you will see that the labels on each bottle state that they contain ibuprofen.

A drug may be ordered by its brand name or by its generic name, so it is very important to pay attention to both kinds of drug names so that you can identify a drug by either one when it is ordered.

2.     Dosage units
These are units which are used to measure the drug's weight or action and are the units used whenever an order is written for the drug.
The most common dosage units are milligrams, grams, micrograms, grains, Units and milliequivalents. 

3.     Administration units
These are units which are used to measure the drug for actual administration to the patient. 
Because it would be very difficult to measure a drug by it's weight or action, we usually measure drugs by their volume or by counting a number of tablets or capsules when we actually want to take out the exact amount we want to give the patient. 
The most common administration units are tablets, capsules, teaspoons, tablespoons, ounces, drops, liters, and milliliters.

4.     Concentration or Dosage strength
This tells us what the relationship is between the dosage units and the administration units. 
Because almost all drugs are ordered in dosage units but administered in administration units, we must have a way to convert from one set of units to the other; this is what the concentration of a drug allows us to do.

5.     Total amount of the drug contained in the package
This is exactly what it sounds like: the total number of dosage units or administration units contained in a particular package of the drug.

6.     Expiration date
All drugs have an expiration date on them, usually prefaced by the abbreviation EXP.; you should always check that the current date is before the drug's expiration date before you give a drug to a patient.

 

 

Addition

The main prescription shortenings

Shorten writing	Complete writing	Translation
aa ac., acid amp. aq. aq. pur. But. Comp., cps., cp. D.   D.S. D.t.d.   Dil. div. in par. Aeq. Extr. f. gt., gtts. Inf. in ampull. in tab. Lin. Liq. M. pil. M. N. ol. Pil. P. aeq. Pulv. q.s.   r., rad. Rp. Rep. Rhjz. S. Sem. Simpl. sir. Sol. Supp. Tab. t-ra, tinct., tct. Ung. Vitr. Ppt., praec. Past.	Ana Acidum Ampulla Aqua Aqua purificata Butyrum Cimpositus (a, um) Da, Detur, Dentur   Da. Signa; Detur. Signetur Da (Dentur) tales doses   Dilutus Divide in partes aequales Extractum fiat (fiant) gutta, guttae infusum in ampullis in tabulettis linimentum liquor massa pilularum misce, misceatur Numero Oleum Pilula Partes aequales Pulvis Quantum satis   Radix Recipe Repete, Repetatur Rhizoma Signa. Signetur Semen Simplex Sirupus Solutio Suppositorium Tabuletta Tinctura Unguentum Vitrum Praecipitatum Pasta	By, equally Acid Ampoule Water Purified water Solid oil Complete Give. Let it be given. Let its give Give. Mark; Let it be given. Mark Give (To give) such doses. Dilute. Divide on equal parts Extract, excerpt Let form (fomed) Drop, drops Infuse In ampoule In tablets Liquid unguent Fluid Pill’s mass Mix. Mixed. Let it be mixed Number Oil Pill Equal parts Powder How much is necessary, how much is needed Root Take Repeat, let it be repeated Root-croops Mark. Let it be marked. Seed Simple Syrup Solution Suppository Tablet Tincture Unguent Glass Precipitate Paste

 

1.     http://www.youtube.com/watch?v=EjScUis24Xc

2.     http://www.zoology.ubc.ca/~biomania/tutorial/solut/pl1fr05.htm

3.     http://www.apchute.com/moa.htm

List of literature

1. Stefanov O., Kucher V. Pharmacology with general prescription. – Kiev, 2004. – 150 p.

2.      Posokhova K.A., Oleshchuk O.M., Shevchuk O.O. Rules of medical prescription writing [Electronic resource]. Methodical instructions for students. Third edition. – 2011. – http://intranet.tdmu.edu.ua/

3.     http://intranet.tdmu.edu.ua/education.php