D.Pharm.

-IIyr, Incompatibility

INCOMPATIBILITIES IN PRESCRIPTIONS Definition When two or more ingredients of a prescription are mixed together the undesired change that may take place in the physical, chemical or therapeutic properties of the medicament is termed as incompatibility. Classification Incompatibilities are of three types: 1. Therapeutic incompatibility 2. hysical incompatibility !. "hemical incompatibility T#$%& $'TI" I(")* &TI+I,IT'sually this incompatibility arises when one or more drugs produces response or intensity different from that intended in the patients. Classification &. )/er doses +. 'nder doses ". Improper consumption by the patient 0. "ontra1indicated drugs &. )/er doses: This can be subgrouped as follows: Excessive single dose 2ometimes a single dose may become o/erdose depending on the health of the patient e.g. a normal dose 3taking body weight as 45 kg for an adult male. may be o/erdose for a lowly built person. #owe/er it should not be more than 2 to ! normal dose. %emedy: The pharmacist should consult the physician and clarify the dose. e.g. 1 %x &tropine sulphate 6 mg henobarbital !65 mg *ake capsules. Label: )ne capsule to be taken three times a day before meals. Comments: In this prescription the doses of both atropine sulphate and phenobarbital are 12 times the normal doses. The physician intended for 12 capsules to be dispensed but he has mistaken or may be it is an incomplete prescription. #ence, before dispensing the pharmacist should consult the physician again. Correct prescription %x &tropine sulphate 6 mg henobarbital !65 mg *ake capsules. 2upply 12 capsules. Label: )ne capsule to be taken three times a day before meals.

D.Pharm.-IIyr, Incompatibility

e.g. 2 %x 2trychnine sulphate 25 mg Iron and ammonium citrate 755 mg repare capsules. 2upply 12 capsules. Label: )ne capsule to be taken three times a day after meals. Comment: 15 times o/erdose of strychnine hydrochloride than that of normal. The pharmacist should consult the physician and obtain the permission to change the dose. Corrected prescription 2trychnine sulphate 2 mg Iron and ammonium citrate 755 mg repare capsules. 2upply 12 capsules. Label: )ne capsule to be taken three times a day after meals. Excessive daily dose In this case the daily dose of drug is exceeded . e.g.1 %x "odeine phosphate 17 mg &mmonium chloride 755 mg repare capsules and supply 28 capsules. Label: Two capsules to be taken e/ery hour for cough. Comment: The '.2. . recommends that the prescribed dose should be taken after e/ery four hours and not e/ery hour. #ence the physician should be consulted. Additive and synergistic co !inations" There are certain drugs possessing similar pharmacological acti/ity. If these drugs are combined together, they may produce additi/e or synergistic action. In such case ad/ice of the physician is necessary. e.g. %x &mphetamine sulphate 25 mg $phedrine sulphate 75 mg 2yrup 9.s. 155 ml ,et a mixture be made Label: Take 27 ml e/ery four hours. Comment: +oth of the drugs are sympathetic stimulants and they are prescribed in their full dose. The formulation will produce additi/e o/erdose effect. #ence, The dose of indi/idual drug should be reduced. 3+. 'nder dose In this type of incompatibility, effect of one drug is lessen or antagonised by the presence of another drug. This can be exemplified by combination of following types of drugs: 1. Sti #lants like nux1/omica, strychnine sulphate, caffeine etc. with sedatives like barbiturates, paraldehyde etc. 2. Sy $at%o i etic or adrenergic like ephedrine, nor1adrenaline with sy $at%olytic drugs like ergotamine. !. Sy $at%etic sti #lants like methamphetamine with $arasy $at%etic sti #lants like pilocarpine. 8. P#rgatives like castor oil, li9uid paraffin etc with antidiarr%eal agents like bismuth carbonates. 7. Acidifiers like dilute hydrochloric acid and al&alisers like sodium bicarbonate, magnesium carbonate.

D.Pharm.-IIyr, Incompatibility

e.g.

%x

&spirin !55 mg robenecid 755 mg repare capsules. Label: )ne capsule a day for gout. &spirin is an (2&I0 gi/en to reduce the pain and swelling in case of gout attack. robenecid blocks the acti/e reabsorption of uric acid from the lumen of nephron, but salicylates 3aspirin. blocks this action of probenecid. #ence, both of the drugs are antagonistic to each other, so its combination is therapeutically useless. 'C( I $ro$er cons# $tion !y t%e $atient" In certain prescription some special directions should be written. If the patients are nor ad/ised the drugs may not produce the desired action due to low bioa/ailability. e.g. %x Tetracycline hydrochloride 275 mg repare capsules. 2upply 15 capsules. Label: Take one capsule e/ery six hourly. Comments: "alcium present in milk inacti/ates the tetracycline, hence a patient may not get any therapeutic effect if he:she takes the capsule with milk. Remedy: The pharmacist should ad/ise the patient to take the capsule with water and not with milk. The patient should not take antacid containing calcium salts. 'D( Contra)indicated dr#gs "ertain drugs should not be gi/en in particular disease condition e.g. 3i. corticosteroids are contraindicated in patients with peptic ulcer. 3ii. ;asoconstrictors are contraindicated in hypertensi/e patients 3iii. 2ome drugs should not be gi/en in asthmatic patients e.g. barbiturates, morphine etc. 3i/.If a person is allergic to a drug 3e.g. penicillin in<ection. then it should not be gi/en to the patient. 3/. "ertain combination of drugs are contraindicate: %x 2ulphadia=ine 5.27 g 2ulphamera=ine 5.27 g &mmonium chloride 5.75 g repare capsules Label: Take two capsules six hourly for cough. Comment: In this prescription ammonium chloride is a urinary acidifier and it could cause deposition of sulphonamide crystals in the kidney. #-2I"&, I(")* &TI+I,IT'sually, this is due to immiscibility or insolubility. It can cause unsightly, non1uniform products from which remo/al of an accurate dose is /ery difficult. Classification: 3&. Immiscibility 3+. Insolubility 3".,i9uefaction

D.Pharm.-IIyr, Incompatibility

3&. Immiscibility 1. )ils are immiscible with water and hence combination of oily drugs with water produces a product possessing two separate layers. Remedy: This problem can be o/ercome by emulsification or solubili=ation. 2. "are must be taken when concentrated hydroalcoholic solutions of /olatile oils such as spirits and concentrated aters, are used as ad<uncts 3e.g. as fla/ouring agents. in a9ueous preparations. ,arge globules of oils may be separated. Remedy: To pre/ent the formation of large globules, the hydroalcoholic solution should either be gradually diluted with the /ehicle before admixture with the remaining ingredients or poured into the /ehicle with constant stirring. !. &ddition of high concentrations of electrolytes to mixture in which the /ehicle is a saturated a9ueous solution of a /olatile oil causes the oil to separate and collect as a surface layer. e.g. This happens in Potassi!m Citrate "i#t!re $.P.C. in which large 9uantity of soluble solids salts out the lemon oil. Remedy: To disperse the droplets e/enly, 9uillaia tincture is added as a wetting agent. 3+. Insolubility 1. ,i9uid preparations containing indiffusible solids such as chalk, aromatic chalk powder, succinyl sulfathia=ole and sulphadimidine 3in mixtures. and calamine and =inc oxide 3in lotions. 1 a thickening agent is necessary to obtain a uniform product from which uniform doses can be remo/ed. 2. 2ome insoluble powders such as sulphur and certain corticosteroids 3hydrocortisone acetate. and antibiotics are difficult to wet with water. Remedy: Wetting agents e.g. saponins for sulphur containing lotions and polysorbates in parenteral suspensions of corticosteroids and antibiotics are used to distribute the powder and pre/ent formation of a slowly dispersing, solid stabilised foam on shaking. !. When a resinous tincture is added to water the water insoluble resin agglomerate forming indiffusible clots. Remedy: This is pre/ented by slowly adding the undiluted dispersion of protecti/e colloid 3%ragacanth m!cilage.. e.g. ,obelia > 2tramonium tincture which should be mixed with tragacanth mucilage and stirred constantly. This will produce a stable preparation. 8. high concentrations of electrolytes cause cracking of soap emulsions 3ionic. by salting out the emulsifiers. ". ,i9uefaction When certain low melting point solids are powdered together a li9uid or soft mass is produced due to lowering of the melting point of the mixture to below room temperature. Thus an e#tectic ixt#re is formed &ny two of the following exhibits this type of beha/iour, camphor, menthol, phenol, thymol and chloral hydrate, also sodium salicylate with phena=one.

D.Pharm.-IIyr, Incompatibility

e.g.

%x Thymol "amphor *enthol 275 mg 2 mg 2 mg

*ake powder. Comments: If these ingredients are triturated together, they will form an eutectic mixture. *ethod1I: &ll the ingredients are triturated. &n eutectic mixture 3li9uid. will be formed. The li9uid is triturated with enough absorbent powder e.g. light kaolin or light magnesium carbonate, to gi/e a free flowing powder. *ethod1II: $ach ingredient is triturated separately with small amount of adsorbent or diluent and then these powders are lightly mixed by tumbling action. and packed. The diluent largely pre/ents contact between the ingredients and adsorbs any li9uid that may be produced. e.g. %x "hloral hydrate 275 mg repare capsules. 2upply 15 capsules. Label: Take the capsules at night time. Comment: "hloral hydrate is hygroscopic in nature. It will absorb moisture and soften the hard gelatin capsule shells and the shape of the capsule may change physically. Remedy: &n e9ual 9uantity of light magneisum oxide should be mixed with chloral hydrate. )ther adsorbents those may be used are kaolin, talc, starch etc. e.g. %x &minopyrine 5.! g &cetyl salicylic acid 5.2 g "odeine sulphate 5.517 g +elladonna extract 5.515 g repare capsules. Comment: In this prescription aminopyrine and acetyl salicylic acid form eutectic mixture and wetting of belladonna extract gi/e green colour. Remedy: ,ight magnesium oxide 3approximately 67 mg. may be added. The half 9uantity of magnesium oxide is mixed with aminopyrine and the other half with acetyl salicylic acid separately. The two are mixed gently and then other ingredients are added and mixed gently.