Prescription Incompatibilities

7/29/2019 Prescription Incompatibilities

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OBJECTIVES:

What are the types of incompatibilities


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The business of the retail pharmacist ofthe present day consisted of three

branches: that of manufacturing

galenical preparations, that of sellingpatent medicines, and that of dispensing

physicians prescriptions.


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There is one department which is stillthe Pharmacists own.

A department which distinguishes him

as a professional man and elevates himabove the ordinary merchant.

And that is


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Incompatibility

According to definition of variousdictionaries, means incapable of existingtogether in agreement or harmony.


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We call a prescription incompatible when its

ingredients are of such a nature that, ifbrought together, one or more of the ff.changes would take place:

1. Mutual decomposition of ingredients2. Precipitation (chemical or physical)

3. Explosion

4. Liquiefaction5. Deterioration of one /more ingredients


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Two classses of incompatibilities:1. Intentional

where the prescriber wants that the

prescription, be dispensed as it is.1. Unintentional

where the prescriber has inadvertentlycombined such drugs as to give unexpectedresults (e.g. precipitation of drug) which is not

what the prescriber wanted.


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In this type, two or more drugs reactto give new compounds which may be

toxic or inactive. Remedy lies inreplacing one or more ingredients ofthe same medical usefulness, yet inert.


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All chemical incompatibilities must be corrected beforethe prescriptions are dispensed unless the prescriber

wants that the incompatible combination bedispensed.

Chemical interactions between the drugs of prescriptionlead to chemical incompatibility. These include:

Effervescence Precipitation

Colour changes

Formation of toxic substances

At times, the incompatibility is immediately apparentand at other times, the changes occur at a slower rateand the incompatibility is not detectable immediately.


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Chemical incompatibility:

It occurs as a result of interaction betweeningredients of prescription. It is of 2 types:

1. Usual chemical incompatibility:

Occurs immediately upon compounding

thats why it is called as immediate incompatibility. It occurseither due to precipitation or color change.

2. Delayed chemical incompatibility:

Mixture reactant such a slow rate

that no appropriate change occurs thats why it is called asdelayed incompatibility. These may occur without immediatephysical evidence of change. It takes sometime to occur. Thismay or may not result in loss of therapeutic activity.


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Precipitation:

When 2 or more pharmaceuticals are combined, a

chemical change may take place with a formation of aninsoluble substance, which precipitates from solution.

Example:

Soluble in organic salts except for the alkali metal reactwith basic hydroxide to yield water insoluble compounds.

Soluble salts of phenol, carboxylic acid and barbituric acidin an alkaline solution will yield the free acid in presence ofrelatively strong acid. Precipitation depends upon the

solubility of these acids in a particular solvent system. Soluble salts of the amine drugs will release free base in

presence of relatively strong base. Precipitation willdepend upon the solubility of this base in solvent system


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Effervescence:Carbonate in the presence of acids, stronger than carbonic acid

will form carbon dioxide. Weak acids such as boric acid will not react withcarbonate.

Oxidation reduction:Oxidation is defined as loss of electron and reduction as the

gain of electron. Oxidation and reduction must occur together and it dependsnot only on the ability of the compound to donate an electron but also on the

ability of the compound to accept the electron.

Example: Phenothiazine tranquilizers are oxidized by ferric ion. Mercurrus salts are easily reduced to free mercury in the presence of moisture,

iron, light or heat.

Stannus salts, of which the fluoride is most important, are readily oxidized byair and most mild oxidizing agents to stannic form. Bismuth compounds are easily reduced to metallic bismuth by organic

compound such as glycerin and natural gums. Silver slats are reduced to metallic silver by light and compounds such as

reducing sugars.


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Color change or formation of color:Various types of chemical changes may result in alteration in color;

the color of medication is often the most important property for patient

acceptance. Occasionally the same mixture may have a slight different color,when compounded a second time or by a different pharmacist. But the actualchanging of the product color is due to the chemical reaction.

Basically there are 2 things to consider: The change in color of pharmaceutical preparation caused by age, exposure to

light and temperature variation. Rapid change in product color occurring at or immediately after mixing.

Most dyes or indicators in pharmacy are acidic or basic and generally form water-soluble ionized salts with anions or cations. The color of these materials isinfluenced by their ionization and thus a change in pH of the solution, that issufficient to effect the ionization, which generally change the color.

Phenolphthalein is a colorless acidic compound. On addition of an aqueous

solution of base such as NaOH . a red ionized disodium salt is formed.Gentian violet is a basic purple compound. However on the addition of sufficient

acid, the compound changes color through green to yellow.


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Hydrolysis:The reaction of the compound with the water divided into 2 broad

categories, Ionic hydrolysis Molecular hydrolysis

Ionic hydrolysis:It involves the reaction of an ionized specie or either hydrogen ion

or hydroxyl ion to form unionized insoluble product. These hydrogen and

hydroxyl ions results in the change in the pH of the solution. Both organic andinorganic salts may undergo this type of hydrolysis.

Incompatibilities resulting from this type of hydrolysis generally manifestthemselves as precipitates of basic salts or hydroxides.

Examples: All zinc salts with the exception of sulfate and nitrate, hydrolyzed readily. All aluminum slats hydrolyzed yielding insoluble basic salts and hydroxides.


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Molecular hydrolysis:It is a reaction of water with organic compounds such

as amides, Easters and lactum. This type of hydrolysis proceeds atmuch slower rate and is often a function of hydrogen orhydroxylion. Because of the relatively slow rate of reaction, molecularhydrolysis is not of major concern to the dispensing pharmacist.

In most cases, the prescription will have been consumed beforesignificant hydrolysis occurs, however this hydrolysis often reduces the

therapeutic efficacy of drug and is not always detectable by a physicalchange.The pharmacist should aware of compounds that may exhibitthis type of incompatibility.

Examples: Aspirin is readily hydrolyzed to acetic and salicylic acid in presence of

moisture. Some antibiotics tend to hydrolyze to inactive form in aqueous

solution. The rate usually depends upon hydrogen and hydroxyl ionconcentration.


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Methods of correction/prevention

of chemical incompatibilitiesReplacement of reacting ingredient:One of the most common types of incompatibility is the

formation of precipitate as aresult of exchange of ions. If the solution isdesired, it is frequently possible to replace one of the reacting substances withanother of equal therapeutic value that will not cause precipitate.

Example of prescription:Sodium citrate 1Calcium bromide 1Simple isopril elixir q.sto make 120ml

MFT solution.

Although both sodium citrate and calcium bromide are soluble in aqueous liquid.They react in solution to form insoluble calcium citrate, which is precipitated.This incompatibility can be prevented by using sodium bromide in place ofcalcium bromide.


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Adding color inhibiting agent:Color changes are sometimes important from the therapeutic

point of view and at the same time,their influence upon the trust of customerand patient. Uniformity in the appearance of prescription and preparation intherefore highly considered. The order in which ingredients are mixed, effectsthe color of finished preparation and it is a good policy for a compounder toindicate on a prescription, the method of compounding used for anypreparation containing colored ingredients.Color change may sometimes beprevented or modified by the addition of inhibiting agent.

Example of prescription:Liquid phenol/phenol 2Iron tincture 4Glycerin 5

Aqua mentha preparata Q.s to make 90ml

MFT solution.

The phenol and iron chloride form an inky black color in solution and the productis very unsightly. By adding citric acid or sodium citrate as an inhibitor, thiscolor formation is prevented and much more pleasant appearance of solution isprepared.


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Oxidation-reduction:Incompatibility resulting from mixing of oxidants and reductantscan be minimized by removal of one of the species.Light catalyzed airoxidation can be minimized by storage in tight container or by theaddition of materials, which will be preferentially oxidized such assodium Meta disulfide.

Hydrolysis:Ionic hydrolysis usually can be prevented or reversed by the

addition of any of the species formed as a result ofhydrolysis.Prevention of molecular hydrolysis is more involved and

require knowledge of conditions that effects stability of drug involved.Whenever the rate of hydrolysis is sufficiently fast to cause significantdegradation of drug beforeit could normally be expected to beconsumed. Correction and prevention of incompatibility is essential.


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Alphabetical summaries of some

incompatibilities Acids, unless very dilute and in small amount, should be

prescribed alone. They combine with bases to form salts,and are incompatible with oxides, alkalies, alkaline salts,

hydrates and carbonates. They all precipitate albumin. Alkalies and Alkaline Carbonates should rarely be

prescribed in solution with other drugs. They form saltswith acids and precipitate many metallic and alkaloidalsalts.

Alkaloidal Salts should rarely be combined with otherdrugs in solutions. They are precipitated by alkalies,alkaline carbonates, earthly carbonates, preparationscontaining tannic acid, and byiodides in solution.
http://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Class-I-Acids.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Iodides.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Iodides.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Class-I-Acids.html


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Bromides in solution should not be combined withalkaloids. They precipitate the salts ofmorphine, quinine,

and strychnine from neutral solutions. Ferric and Ferrous Salts should generally be prescribed

alone. They are incompatible with tannic acid and all drugscontaining it; with alkaline carbonates, ammonia, andacacia.

Resins, including oleoresins, and fluid extracts and tinchires containing resins, should not be prescribed in waterysolutions, though they may be ordered in emulsion bysuspending them with the mucilage of acacia ortragacanth. They are all precipitated bywater.

Silver Nitrate solutions and solutions of all silver salts mustbe ordered alone, and kept in dark bottles. If silver salts areprescribed for internal administration they must be aloneor combined with some earth, and given in capsules.
http://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Bromides.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Morphine.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Strychnine.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Local-Treatment-Of-The-Skin.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Local-Treatment-Of-The-Skin.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Strychnine.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Morphine.htmlhttp://chestofbooks.com/health/materia-medica-drugs/Introduction-to-Materia-Medica-and-Pharmacology/Bromides.html


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SOURCES: PRACTICAL PHARMACEUTICS by: Dr.P.V. Kasture

http://home.us.archive.org/stream/treatiseonprescr00robiuoft/treatiseonprescr00robiuoft_djvu.txt
http://home.us.archive.org/stream/treatiseonprescr00robiuoft/treatiseonprescr00robiuoft_djvu.txthttp://home.us.archive.org/stream/treatiseonprescr00robiuoft/treatiseonprescr00robiuoft_djvu.txthttp://home.us.archive.org/stream/treatiseonprescr00robiuoft/treatiseonprescr00robiuoft_djvu.txthttp://home.us.archive.org/stream/treatiseonprescr00robiuoft/treatiseonprescr00robiuoft_djvu.txt


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Therapeutic Incompatibility in this type, problemsarise by combining drugs or doses prescribed. It is theresponsibility of a physician. However it forms a part

of the duty of the pharmacist to bring this problem tothe notice of the prescriber

Prescription Incompatibilities

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