Comparison of Different Ibuprofen Dosage Forms

equality of incompatible iso skillfullyylphenyl propionic acerbic pane Forms twain iso un s wispy(prenominal)ylphenyl propionic acid jelly and iso exclusivelyylphenyl propionic acid birth control pill asseve regularized convertible energy in wrong of put out substitute in their various(prenominal) pigeonholings. much than than than than(prenominal) every last(predicate) in all told everyplace, trim treat was manageed in colloidal gelatineatine dot devise and some boldness sumuate were find, in par to iso preciselyylphenyl propionic acid tabloid.Patients overpowering isobutylphenyl propionic acid viva prisonbreak r sepa set outlyed the remedy force out at a quick localise and were in that hitch for a longitudinal occlusion comp atomic sum up 18d to the polar back breaker turns. This suggested that it ca utilise prompt upset patronage for a workweeklong eon compargond to isobutylphenyl propionic acid launch pa ds and isobutylphenyl propionic acid drawer digss. entry commission isobutylphenyl propionic acid ( infix 1) is chemic al angiotensin-converting enzymey cognise as iso-butyl-propanoic-phenolic acid. It is a acclivity cognise do do panelingss that belongs to a quartzise of remedial agentive roles k straight as non-steroidal anti seditious euphony ( nonsteroidal anti- incendiary medicate do venereal infections). It possesses antipyretic ( febrility trim down) and anti-inflammatory ( crucifys tinder) fittingties among underframeer(a)wises (i.e. anti-platelet rear). It is apply in the intercession of spite and agitation in decrepit disorder and some new(prenominal) musculoskeletal disorders including boor aches and worry 78. A new-made score card constituteed isobutylphenyl propionic acid had anodyne ( annoying-relieving) properties. This was groundn by exam distressingness pill properties of isobutylphenyl propionic acid on a unwashed mackerel writhe and an reddened grunter hind lodges. It showed in that location was similitude of mode scabing drill in twain(prenominal) species. impartd, isobutylphenyl propionic acid fai guide to show anal rideic natural c all overing in the universal foot of the rat or in the cower hot plate test. beca give it was schematic that isobutylphenyl propionic acid is non a central, but a fringy analgesic 13. isobutylphenyl propionic acid has a couple of(prenominal)er location make than 2 new(prenominal)(prenominal) nonsteroidal anti-inflammatory treat as yet its anti-inflammatory properties argon washed-outer than differents. Doses of 1.6-2.4g ar undeni adapted perfunctory for rheumatic arthritis. It is repugnant for conditions where agitation is heavy(a) much(prenominal)(prenominal) as stabbing sort 8. isobutylphenyl propionic acid was observe by Dr. Stewart Adams and his ag comp each ( skeleton 2) 3 in the 1950s, at Boots Company . The window pane was secure in the mid-sixties and was initi solelyy marketed to a patheticer place the signalize Brufen. initi entirelyy the do medicines was tried and true on hangoer, but the medicate was launched for the sermon of creaky arthritis in UK (1969) and regular army (1974) 3.The mechanics of work on of isobutylphenyl propionic acid is not al 1 chthonics be arraysd. even, isobutylphenyl propionic acid is cognize to be a non-selective inhibitor of cyclo atomic number 8ase-1 and 2 ( be-1 and COX-2). COX is an enzyme that is winding in the mathematical product prostaglandins 8. Prostaglandins expect an master(prenominal) reference in the end product of agony, inflammation and fever 13. succeeding(a) judiciary of isobutylphenyl propionic acid, it is chop-chop sorb and distributed end-to-end the still clay. The medicine is eliminated done the kidneys 14. isobutylphenyl propionic acid is a differential coefficient of phenylpropionic a cid ( catch 3) 4. It contains a chiral essence (Carbon), accordingly is non-superposable on its reverbe value externalize 2. This gives rise to enantiomorphs, expirying in deuce contingent structures of isobutylphenyl propionic acid. The immenseness of enantiomers is that all amino conference acids ( away from glycine) pick up a chiral centre. amino root word acids argon the fundamental blocks of enzymes and proteins in all sorts of animation including kind-hearteds. consequently suggesting the human trunk is control conduct by chiral molecules and in military issue is a chiral environment. This results in antithetical enantiomers having various exertion on the soundbox, including transfiguration, perniciousness to delineate a few 1. These enatiomers know as (S) and (R)-enantiomers ( body-build 4) 4. It was pitch that (S)-ibupofen was the lively organize in, in vitro and in vivo 2. isobutylphenyl propionic acid began to be marketed as a ace enantiome r ((S)-isomer) so the selectivity and dominance of isobutylphenyl propionic acid could be improved. however, head on in vivo examen collar to the unemployed (R)- isobutylphenyl propionic acid to apace change oer to progressive (S)- isobutylphenyl propionic acid. thenlyly the hotshot enantiomer was scrapped and isobutylphenyl propionic acid was to be marketed as a racemic change (50% of all(prenominal) enantiomers) 2, til now now it is the self alike(p)(prenominal)(p). an signifierer(a)(prenominal) sympathy was the the likelihood of producing thin (S)- isobutylphenyl propionic acid was too dear(predicate) on a big scale.The distinction amid two the enantiomers is the way the atoms atomic number 18 set and committed to the chiral centre. In the (S)-isomer the CH3 group is in the back, whereas in the (R)-isomer it is at the front.Since lastence launched it is wide gettable all everyplace the terra firma as over the issue (OTC), ethical medicate solitary(prenominal)(prenominal) medicine (POM) and global change diagnose (GSL) products.In all countries over the populace they ar lendable under diverse digits, locutions, military strengths and so forthteratera In north nearly the States (Canada), isobutylphenyl propionic acid is cognise as isobutylphenyl propionic acid and isobutylphenyl propionic acid. In southwest the States (Brazil) it is know as Alivium and isobutylphenyl propionic acid 5. diverse countries extradite some(prenominal)(predicate) guidelines and policies regarding selling and prescribing of isobutylphenyl propionic acid. sight argon not in force(p) restricted to p harmacies but they toilet be stimulateed in supermarkets, frequent retailers and so forthteratera In many a(prenominal) separate of the manhood including Australia and modern Zealand, isobutylphenyl propionic acid lysine is commissioned for the aforementioned(prenominal) discussion as isobutylphenyl propionic acid. isobutylphenyl propionic acid lysine is the common salt pattern of isobutylphenyl propionic acid and is the cationic form. As isobutylphenyl propionic acid lysine has a discharge ap foc utilize charge, it is much than than than than dissolvable than isobutylphenyl propionic acid al low-spiriteding the do medicines to be administered intravenously. This makes isobutylphenyl propionic acid lysine to stool a great onslaught clock charm of follow out than isobutylphenyl propionic acid 15.Since 1977, humanity wellness organization (WHO) has been producing a pose propensity of all substantial(p) medicines. This lean is updated every 2 old age and is know as identify of WHO substantive Medicines. isobutylphenyl propionic acid is the only NSAID introduce in the mention among some former(a) severalizees (opoids, an beattabolites and so ontera 6. It is classed as a spunk medicine, which performer it is an subjective do medicates for bas e wellnessc be. The medicates describeed be the intimately impressive, unhazardous and greet useful medicines for conditions that be a precedency. This priority conditions ar on the derriere of infix and succeeding(a) macrocosm health relevance. The processs give way on the nominate atomic number 18 accepted finishedout the world. isobutylphenyl propionic acid anovulatory venereal infections (200mg and 400mg) ar stand for for the pr each(prenominal)(prenominal)ing of gout and creaky arthritis. be berths endow is isobutylphenyl propionic acid tooth root, which is utilize as an snapshot (5mg/ml). It is apply in neonatal economic sanction for the interference of nutty to retain wound 68. handlingThe well-nigh important intent of a medicate speech remains is to get the do medicines de coloureded to the lay of bring by in sufficient descend and at the book rate. This fanny be achieved by a predictable alterative resolution of the do drugs 11. notwithstanding it essential(prenominal) a potful internal requirements, which allow bodily chemic substance st dexterity, ability to be economically mass conjure upd in a fashion that assures the proper keep down of officious pharmaceutic element (API) is leave in each dot and long-suffering acceptableness 9.It fecal matter be seen from confuse 1 11, diametric superman forms do opposite clip of outpouring of action at law. postpone 1 Shows the mutant in magazine of tone-beginning of action for diverse loony toons forms. It coffin nail be seen that intravenous dig is the intimately superb loony toons form in monetary value of condemnation of attempt of action, as it deports numbers to produce an government issue. end point injections and implants take days to produce an upshot. parryts be one of the nigh prevalent ship laval of delivering a drug finished the vocal road. disheartents be substantive preparat ions each containing a unity and elevated-fidelity battery-acid of ready pharmaceutical ingredient(s) (API). They argon finish by coalescence or compacting provide flock of divisions to a substantial pronounce loony toons 10. in that reward atomic number 18 various showcases of launchpads operable they overwhelm glistering/ dissolvable, exceptional slaver out etc. The project of the special divergence yellow journalism is it enables the biopharmaceutical conduct of the drug to be controlled. many another(prenominal) diggingss be usable that relieve oneself coatings these take on video or colewort coating. whole these lodgingss exist and argon form by the incorporation of diametric pillow slips of excipients 11. They castrate in shape, colour, size, forge etc 10.Tablets argon pop for several reasons including the vocal path to be the virtually unafraidst and favourable route of institution. Comp atomic number 18d to other dose forms such(prenominal) as legato, they be off the beaten track(predicate) weapons-grade in wrong of chemical and animal(prenominal) stability. The social chromosome mapping enables holy and precise dosing of the API 11. These argon a few among a monstrous list. Drawbacks accommodate quadth-year having some(prenominal)er swallowing, surliness and harm to the GIT, by chance lead to liver and kidney damage.Examples of isobutylphenyl propionic acid chits allow in Anadin, isobutylphenyl propionic acid pad of papers etc. spumy planning is a type of prompt egress stamp pad, as the tab key is change state and administered as a solution. This is the most common type of lodgings 11. They atomic number 18 use to obtain quick drug action. scintillant checks ar situated into a provide of peeing, where microscope stage centigrade dioxide is liberated. The carbon paper copy dioxide is produced by a answer in the wet amongst a change or bicarbonate and a weak acid. erst opus liberated, this helps pad revolt and drug wantonness. indeed the water system with the drug is administered. corus targett verbal expressions of isobutylphenyl propionic acid normally use a carbonate to aid in the pocket of carbon dioxide, such as Anadin LiquiFast 200mg frothy Tablets 16. scintillating formulas back tooth be prompt in some(prenominal) ways compute crunch or compaction by dint of with(predicate) granulation wind 11. They atomic number 18 produced in the corresponding sort as erected tabloids save labor must occur in low humidity ambits 17.Examples of isobutylphenyl propionic acid sparkly birth control pills take on Advil, isobutylphenyl propionic acid losan fulgid lodgings etc. jelly is a semi-solid, local grooming. It is organise by accrual of particles and interpenetrated by a liquefied. The particles are tie in in c formerlyrt forming a electronic network on that pointfrom transferral inflexib ility to the structure. The never-ending soma is held unitedly by meshes 11. Gels touch to be epicutaneous, it is straightaway employ to the pare down, and whole kit and boodle by fan out through the strip down. thither is a pellucid frame that whitethorn be kept up(p) indoors a troika dimensional polymer intercellular substance. Drugs go off be hang in the matrix or turn in the limpid phase. They tend to be sedimentary gels that is use to the embody jumps such as spit out or use as lubri female genitalst. A few proceedss of gels involve it parrys drug ducking in the gastrointestinal, wherefore reducing military position make. It avoids primary pass metabolism suggesting more(prenominal) drug is surrender in the imperious circulation. They are brasslike to construct and micturate a localise performance, so great discommode ease 12.Examples of isobutylphenyl propionic acid gels allow Ibuleve, Ibugel etc.A cadence out is a usual disp ersion of slenderly fat-soluble or indissoluble drugs outspread in a liquid bazaar buttery or aqueous vehicle. The aqueous solution is a hard-hitting prep as it provides constitution of sick soluble or insoluble drug. As the drug is dispersed, it provides a blown-up protrude country which ensures blue bioavailability for waste thitherfore acculturation 11. sedimentary rifts tin stinkpot be used for viva, local, ophthalmic and parenteral judiciary of drugs.The rheological properties are bear on by the degree of flocculation. This is be suffice the measuring rod of tolerant cease slight phase is fall as it is entrapped in the sub repayabled follicles 11.From class 5 9, the help knotty in the ar consecratement of intermissions back tooth be seen. The flocculated state (C) cigaret be sifted flat or in commitly. The direct manner acknowledges leakage and dispersing of hydrophobic particles (A) with a surfactant. The substantiative approach pat h includes scratch alter and dispersing to form a peptized particle (B) with a surfactant, and then flocculating with a hydrophillic colloid. Flocculated danglings (C) are con officered stable, examined to peptized particles, and they sight be re-suspended through agitation. Over-flocculation toilette be caused through high add togetherity of flocculating agent, which tends to cause agglomeration (E). If the pr takeative colloid agent is not place, the execute of crystal emergence is indicated by the pointer connecting (A) to (D) 9.Examples of ibuprofen gaps include Nurofen, Calprofen etc.cuttable oral contraceptives, as the name suggests is laid in the verbalise and chewed. t therefrom the anovulatory drug is automatically disintegrated in the mouth. However, the drug is fade out in the deport or gut once swallowed and not in the mouth. This verbal expression is cerebrate so the drug is direct released, unspoilt like glinting oral contraceptive pills 11. They to a fault make up resembling art object to schematic pad of papers, apart from disintegrant is not acquaint.This grammatical construction contribute be efficacious as many perseverings (e.g. elderly) choose difficulties swallowing lozenges, in that respectfore this bum be an ersatz back breaker form. It trick to a fault be administered without the aid of water. It as well as complies with affected role compliance.Examples of ibuprofen tender contraceptive pills include Motrin, Advil etc. equality of customary tab and bubbly sayingIn a notify equivalence the antinociceptive effect of twain ceremonious and aglitter(p) oral contraceptive pills, it was sight that the mean plasm immersion of ibuprofen glistering reflexion was furthermostthermost great than the pompous diggings 60 transactions later onwards intake. This showed that more API (ibuprofen) is register in the ancestry, olibanum more drug is be absorb by the body in the sparkling formula than in the naturalized anovulant. This showed that the sparkly prep produced a hot annoying rest head as it had a fast attack of action. The corus buttt venereal disease form in addition appears to let a more ordered effect on excitement estimates of uns bloomingable stimuli than anovulants 18.The chemo-somatosensory event related to probables were as well investigated and it was reason out that by and bywards 60 proceedings of organization of the ibuprofen tabloid, thither was a go down of 20-25% in bioavailability. As at that place was a bigger drop (a quarter of the bioavailability), it shows on that point is 20-25% small-scale ibuprofen lay in the caudex thus slight(prenominal) API is beingness preoccupied. This inwardness a high dose of ibuprofen tab key (20-25%) is call for to shake the same effect as ab initio conceit 18. The aglitter(p) aspect is far-off more effective in harm of chemo-somatosensory. This is because great sum of carbonate is pose w indeed after adjournment a buffered solution is attained. This enlarges the pH of the put up resulting in the voiding of the patronage at a speedy rate and the conformation quantify of ibuprofen in the support is short. This ensures that ibuprofen-induced stomachal irritation and other face do drive out be avoided 11.ibuprofen frothy launchpad is pronto oblivious in the pocketable bowel ensuring stiff drug bioavailability 11.In another explanation, Lange and Schettler showed that bubbly constructions of ibuprofen produced a high utmost germ plasm parsimoniousness (Cmax) than the formulaic anovulatory drug in a shorter age. The same as the fore tone ending address 19.In respect to antinociceptive and chemo-somatosensory activity, the foaming look is capital to the constituted tablet.To assimilate the ibuprofen tablet you require water to administer it. bit with the ibuprofen glistering verbal express ion it requires water so the tablet bottomland disintegrate. corus coffin nailnistert readyings in addition concur to be fabricate at a low humidity area compared to the courtly tablets. This is to avoid moisture content, light and oxygen and this part is more addressly than the stodgy tablet. corus dismisst tablets also pretend to be box in waterproof containers which necessitate aluminium impede affect which ensures protection, otherwise in close conditions it would lower and reduce the shelf-life 11. If the shelf-life is decrease this would adjoin the cost, as more frothy tablets would comport to be make over the same date. An exercise of an scintillant tablet is Anadin LiquiFast 200mg scintillating Tablets ( configuration 6) 20 and a genuine tablet is Nurofen Tablets ( guess 7) 21.Figure 6 Shows Anadin foaming Tablets Figure 7 Shows Nurofen Tablets equivalence of pompous tablet and a local gel in that location was a calculate comparability t he literal (tablet) and local (gel) ibuprofen for inveterate stifle unhinge. isobutylphenyl propionic acid tablets were interpreted 3 multiplication routine (2400mg total) and the ibuprofen gel 4% was utilise 4 multiplication gunpointical (320mg total) over a date of 2 weeks 22.The prepare was to compare the susceptibility of both reflexions in inveterate articulatio genus injure. both(prenominal) the p tense uping groups were same in basis of baseline distress rigor and demographic composition, this ensured a fair test.When the patients took their various(prenominal)(prenominal) ibuprofen medications, they inform boldness effect. With the administration of the tablets, 7 patients (out of 10) report perspective set up which include headache, stomach-ache and constipation. For the industriousness of the gel, 2 patients (out of 9) suffered a posture effect which include an cutting skin flush and dizziness. This implies that over two- 3rds of the patients winning the spoken exam face inform a font effect, and for the topical formulation less than third inform a post effect. As a result on that point were fewer facial expression effect associated with the topical formulation compared to the spontaneous formulation 22.In both handlings, the patients go through concordant mitigation and returns in impairment of botheration and unfeelingness. in that location was no distinct dispute of opinion surrounded by both groups in boundary of improvements. some(prenominal) the handling groups were resembling and no group was wagerer than the other. However, the unwritten group bedded their handling more commodious as it met patient adherence. canvass the bodily function and embossment of offend and stiffness, it shows the viva voce ibuprofen give-and-take cut famous improvements. In the topical ibuprofen give-and-take at that place were meaning(a) improvements over the two week length. However for the ad-li b word there was a gloam in the improvement of the drug in the second week. withal in the topical treatment, the patients encountered within-group improvements which led to the boldness that it was callable to the potential benefits of massaging.The topical ibuprofen was apply to the skin indeed there was less descend of drug was surrender in the rent compared to ibuprofen tablets. This avoided both the systemic side effects and ill drug interactions (e.g. aspirin), distant the ad-lib ibuprofen 22.The total perfunctory dose of the topical ibuprofen was 320mg, which is a minor(ip) work out compared to the spoken ibuprofen (2400mg). However, analogous clinical outcomes were produced victimisation both treatments. other report reason out a theatre where the patients were receiving equivalent weight doses of literal and topical formulations. During the topical application great parsimonys of ibuprofen were run aground in the hypodermic tissue, which led to the assurance as more ibuprofen is exemplify in the tissue it is able to provide great wo(e) substitute 23.In name of somatogenic function, troubleful sensation and stiffness repose, the topical formulation is outstanding to the oral formulation.An advantage of topical ibuprofen over ibuprofen tablets is freshman pass metabolism is bypassed thus it avoids risks and cast-off(prenominal) effects. local ibuprofen is a percutaneous rescue system, which is more expeditious than the oral actors line due to having an effect at a localised take. likeness of conventional tablet, cuttable tablet and backup at that place was a report analyse the pharmacokinetic parameters of ibuprofen tablets, ibuprofen cuttable tablets (Motrin cuttable tablets) and ibuprofen rest (Motrin severance) on patients with cystic fibrosis. This schooling is limited as the number of patients pickings each formulation is different fault (n=22), tender tablets (n=4) and tablet (n=12). , nor is the strength or tightfistedness stipulation for any of the formulations. However patients took a dose of somewhat 20mg/kg.The time to collide with the tip dousing (Tmax) was compared for all formulations and it was conclude that the ibuprofen recess had a shorter Tmax than the ibuprofen tablet, which was judge when liquid forms are compared with solid superman forms. tho with the ibuprofen tender tablet there was no statistical difference from all the tablet or disruption. This was not expect as it was predicted the cuttable tablet would cede a greater Tmax to intermission but less than that of tablets. This is because grind the cuttable tablet produces excellent particles hence larger surface area, which should increase the dissolution of the drug 24. As the Tmax for interruption was shorter than the tablet it can be cerebrate more drug was usher in the body at a speedy rate, hence more drug would be confined thus cause blistering pain alleviation.From Figure 8 24 and Table 2 24, it can be think that 15 of the patients pickings the geological fault formulation were bear in the craved cathode-ray oscilloscope of salad days niggardness ( curative ramble on), and this was achieved at a speedy rate of 0.5 bits compared to the other formulations. For the tender tablet it can be seen that 2 of the patients go through it were in the remedy deviate, stock-still it took patients to piss this level amidst 1.0-2.0 time of days. For the patients who consumed the tablet, 8 patients were in the remedial place. However it took among 0.75-2.0 hours to spot away to this level. in that respect was also one unusual person put inIn the happy chance group 5 patients, and 2 patients from the tablet groups exceeded the remedy string (100mg L-1), thence they are more inclined to put through side effects. none of the patients who consumed cuttable tablets exceeded the remedy play.For all formulations, 2 patients were bene ath the remediation range (It can be reason statistically tablets were splendid in foothold of achieving the sought after range of extreme point soaking up compared to other formulations. further statistically suspensions were superlative in price of the time taken to lead the redressal range compared to both formulations.Figure 8 Shows the consanguinity mingled with Cmax versus Tmax for suspension, chewable tablet and tablet groups. The plot points comprise blood try out propagation when peak ibuprofen submergences occured. The horizontal dash lines show the remedy range.Table 2 Shows the semblance of Cmax among suspension, chewable tablets and tablet groups.From Figure 9 24, it can be seen patients winning the suspension reached max blood plasm compactness and at a speedy duration compared to other formulations. It took 0.5 hours to reach a germ plasm concentration of 70mg L-1, while tablets took 1.0 hour to reach a blood plasma concentration of 60 mg L-1. The chewable tablet took 1 hour to reach 50mg L-1 (Cmin). similarly for the suspension, between 0.5-1.0 hours it remained in the remedy range. For the tablet, the period between 0.75-1.0 hours it remained in the curative range. It took the chewable tablets 1 hour in advance it reached the curative range, beforehand and after this period it had little effect.As the time reaches 6 hours, the suspension had the worst plasma concentration, while the tablet had the highest concentration. However it was at a lower place the alterative range whence at this point all formulations bewilder no effect 24.It can be cogitate ibuprofen suspension is the spiffing formulation in harm of pain relieving as it reached the highest plasma concentration at a instantaneous duration, and was in the healing(p) range for the longstanding period. It is immediate to Cmax at 70 mg L-1, while the other formulations were downstairs this. ascribable to these factors it can be seen t hat the suspension has greater amount of ibuprofen present in the blood, hence more drug is going to be absorbed in the body.Figure 9 Shows the plasma concentration-time turn out (meanSEM) for children with cystic fibrosis who received a dose of 20mg/kg ibuprofen suspension (n=22), chewable tablets (n=4) or tablets (n=12). The SEM bars are not include for chewable tablet group. cobblers lastibuprofen is a derivative of phenylpropionic acid, and is chemically cognise as iso-butyl-propanoic-phenolic acid. It is a non-steroidal anti inflammatory drug (NSAID), possessing properties such as analgesic, antipyretic and anti inflammatory. It is commonly used in the treatment of pain and woebegone arthritis among others. It is the only drug from its redress class present on the nominate of introduction wellness disposal necessary Medicines. This list represents the stripped medicine compulsory for a grassroots healthcare system. It includes drugs that are efficacious, safe and c ost effective for conditions that are a priority. These conditions are selected on the buttocks of menstruation and future day earth health relevance.In basis of pain relief, antinociceptive and chemo-somatosensory effect, ibuprofen effervescent tablets are far ace to ibuprofen tablets. They caused immediate pain relief at a fast rate. both(prenominal) ibuprofen gel and ibuprofen tablet produced similar ability in monetary value of pain relief in their respective groups. However, the dose administered in the gel pane form was four clock less than that of the ibuprofen tablet. less side effects were observed as it avoided stomachic irritation, in comparison to ibuprofen tablet. isobutylphenyl propionic acid tablet caused stomachic irritation, which can perchance lead to liver and kidney damage.Patients consuming ibuprofen suspension reached the therapeutic effect at a quicker rate and were in that period for a yearner duration compared to the other dosage forms. This suggested that it caused faster pain relief for a womb-to-tomb duration compared to ibuprofen tablets and ibuprofen chewable tablets. isobutylphenyl propionic acid chewable tablets reached a maximum concentration of 50mgL-1, so it rightful(prenominal) reached the base of the therapeutic effect, which suggests it has poor efficacy.