Ir aq i J.Pharm.Sc i., Vol.15 (1 ) ,2006 63 Clinical Evaluation of a Formulated Econazol Nitrate as A Topical Solution Laith H. Samein* Received 5-9-2004 Acce pted 20-2-2005 ABSTRACT Econazole nitrate (EN) is c ons idered as the mos t e ffec tive age nt fo r the tre atment o f a ll fo rms of d ermatomyco sis ca used by derna to phytes. It was formula te d as a top ical solution in our labo ra torie s. This s tudy was designed to eva luate the e ffec tive ness o f Eco na zol Nitrate in the prepa red formula and co mpared with that o f c omme rc ial b ra nd , P ev aryl®. A to ta l of 104 pa tient suffering fro m de rma to myc oses were invo lv ed in this inv es tiga tio n. Bo th formula were ap plied to the a ffe cted skin re gion in the morning a nd ev ening from wee k to 16 wee ks with light mas sa ge until comp le te hea ling effe ct was achieved . The data revealed tha t the pe rcenta ge of cured patient trea ted with the p re pared fo rmula a nd reference formula o f Ec anozo l Nitrate 1% so lution were 90.3% and 88.4% respec tively also c hronic cases could be la rgely cure d by tre atmen t with the p repa red fo rmula Econazol Nitra te 1 % solution. The results o f this clinical inves tigatio n showed that the p repa red fo rmula o f Ecano zo l nitra te 1% was effe ctive as comp ared to that of the commercial b ra nd, Pevaryl®. الخالصـــة ستخدام هذا الدواء في عالج جميع اشكال الفطريات الجلدية الناتجة عن العوامل يعتبر االكثر فعالية ال) نترات االيكانازول (ان محلول  والذي حضر في المختبرات الصناعية لكلية ( لقد تم تحضير الدواء على شكل محلول لالستخدام الموضوعي . المسببة لتلك الفطريات  المستحضر التجاري بيفاريل كمستحضر قياسي فوجد ان لقد اجريت دراسة سريرية مقارنة بين المحلول المحضر صناعيا و) الصيدلة كال العالجين أظهر فعالية في تقليل االعراض المرضية لكن العالج بواسطة محلول . كل منهما له نفس التاثيرات العالجية والجانبية  التجاري بيفاريل . نترات االيكانوزول كان اكثر فعالية   إلى ان محلول نترات االيكانازول والمستحضر  اعطي اشخاص  104قد ايضا ممكن عالج االصابات المزمنة بصورة . كمجموع كلي يعانون من فطريات جلدية ناتجة عن العوامل المسببة لتلك الفطريات  ان محلول نترات االيكانازول والمستحضر التجاري بيفاريل . المحضر سابقا% 1كبيرة باستخدام محلول نترات االيكانازول بتركيز  اسبوع مع مساج خفيف على المنطقة المصابة  16عا على المنطقة المصابة من الجلد في الصباح والمساء لفترة من اسبوع إلى قد وض .حتى تم شفاء المنطقة المصابة INTRODUCTION Eco na zole nitra te is (RS ) –1 -[2,4 dioc hloro- B (P - chorobe zyl- oxyphe ne thyl] i mid azole nitrate (1). CH2 CH – O CH2 - It is a white o r a lmo st white crystalline p owde r. M.p. a bout 164, with dec ompo sitio n, v ery slightly s olub le in water and e ther: s oluble 1 in 125 o f e thano l (96%) 1 in 60 Of c hloroform and in 25 of methanol (1,.2). Eco nazole nitrate is use d for the top ic al trea tme nt of all forms of d ermatomycos is cause d by de rma to phytes like tricop hyton rubum, tricop hyto n menta groghytes tric op hyton tons us ra ns whic h c aus e tinea ped is , tinea c ruris : and tinea c orp oris re spe ctiv ely (3). It is us ed for d ermatomycos is cause d b y yea sts like c and id a albicans and condida guillie rmord i (4). *Department of Pharmaceutics , Co llege of Phar mac y, University of Bagh dad, Ba ghdad - Iraq N N Cl Cl Cl .HNO3 Ir aq i J.Pharm.Sc i., Vol.15 (1 ) ,2006 64 Eco na zole nitra te is av aila ble in a va riety of dos age fo rm such as s kin crea m (alone or in co mbination with triamcino lo nc ), s kin so lution, s kin lo tion, v agina l s upp ositorie s and sp ra y solution (3) . It has be en prove n to be e ffe ctiv e in the pres enc e of mixed infection. The a ntib ac te rial effe cts of the p re paration offer on a dditio nal ad vanta ge . The purp ose of this wo rk is to e valuate clinically a s elected formula fo r Econazole nitra te as topica l solution prep are d in our la borato ry (5). SUBJECTS and METHOD A total of 10 4 pa tients w ere involve d in this inv estiga tion. They were diagno sed b y Dermatologis t Dr. A. Al- S wdany working in med ic al c ity a s ha ving de rmatomycetes cause d by v ario us d ermatomycetes , b la stomyce te s and mould ( 6 , 7 , 8, 9 , 10). The p atie nts age ra nged from 17 -7 0 yea r (ave ra ge 6 3.4 yea rs ). The y were ra nd omly divided into two gro up s (5 2 patient in e ac h ) the patients in group 1 , were 17 fe male (3 3%) and 35 males (67 %) were instructe d to use the p re pared formula of ec ona zo l nitra te 1 % s olutio n. Patients in group II, w ere 16 fema le s (3 0%) a nd 36 males (69 %) were give n the co mmercial of e conazol nitrate 1% s olution, P eva ryl® Ciliag. All pa tients were instructe d to a pply e conazol nitrate twic e da ily with light mas sa ge o n to the affe cted s kin re gion. The d uratio n of tre atment was range d from one wee k to 16 wee ks . RESULTS and DISCUSSION All p atie nts involve d in this study were ev aluated clinic ally, in ad dition to myco lo gical and micros cop ic al examina tion be fo re and after trea tme nt with e ithe r the prepa re d fo rmula of e conazol 1 % s olutio n or P eva ryl® CLINICAL EVALUATION The re spo ns e to the trea tme nt wa s grad ed as , cured ,po or improve ment and no effe ct (7). The data s howe d that the perce ntage of c ured, poo r imp ro vement a nd no e ffec t in pa tients tre ated with e co nazol nitra te 1% so lution (the prep ared formula) we re 9 0.3 %, 7.8 % and 109 % res pec tive ly as s how n in ta ble -1 . Table :1 Clinical e valuation of 52 pa tie nts ta king Ec onazole 1 % s olut io n. No. o f pa tie nts 5 2 1 00% Cure d 4 7 90.3 % Poo r impro ve me nt 4 7.8% No e ffe ct 1 1.9% The res ults o f patient trea te d with Pev aryl® solution s howe d that 88.4 % we re c ured, 9.7 % of po or improv ement and only 1.9% with no effe ct a s illus trate d in tab le -2. Table –2 Clin ic al e va luatio n of 5 2 patie nts taking Peva ry l® as a re fere nce . No . o f patie nts 52 1 00% Cure d 46 88.4% Poor impro ve me nt 5 9.7% No e ffe ct 1 1.9% MYCOLOGICAL EVALUATION P rior to the ra py the fungus spe cies c ould be demo ns trated by a p ositiv e c ulture in 20 patients out of 52 pa tients treate d with either the prepa re d fo rmula o r re fe re nc e (Pe va ryl®) of e conazole nitrate 1 % s olutio n. Tab le –3 - showed tha t no more fungi we re prese nt in 14 patients , (7 0% ) tre ated with eco na zole 1% so lution while 6 pa tie nts could not be c hec ke d myc ologica lly, as there were no samples av aila ble due to he aling of myco sis. Myco lo gical e xa minatio n in patient treate d with (Pev aryl®) showed nega tiv e fungi in 13 patient (6 5%) a s shown in table 4 . Ir aq i J.Pharm.Sc i., Vol.15 (1 ) ,2006 65 Table –3 Mycologica l e valua tion o f 20 patie nts ta king Econazole 1 % s olutio n. No. of patie nts 2 0 100% Fung us ide ntific atio n pr io r to the ra py + Afte r the rapy - Cure d 1 4 7 0% Fu ngus ide ntifica tion Prio r to the ra py + Afte rthe ra py cure d No sa mple - ( cure ) 6 3 0% Table –4 Mycologica l e valua tion o f 20 patie nts taking Pev ary l® as re fre nce . No. of patie nts 20 100% Fungus ide ntification prior to the rapy + Afte r the rapy - - c ure d 13 65 % Fung us ide ntific atio n Prior to the rapy + Afte r the ra py c ure d No s ample - ( c ure ) 6 30 % Fungus ide ntification prior to the rapy+ Afte r the ra py + not c ure d 1 5% MICROSCOPICAL EVALUATION The diagnos is was also c onfirme d by pos itive mic ro sc opica l fungus id entifica tion prior to therap y in 25 pa tients tre ated with eco na zole 1% s olutio n o r Pev aryl® .The perce ntage trea te d with e co nazole 1% so lution and Pe varyl® w ith a negativ e funge s we re 80% and 76% resp ec tive ly a s s hown in tab le 5 and 6 .Microcs op ic al e xa mination co uld no t be performed in 4 c ase s (16 %) treate d with eco na zole 1 % and 5 c as es (20 %) used Pev aryl® , sinc e no s amp le were ava ila ble due to hea ling o f myc os is . Table –5 Mic ro sco pica lly results of 25 pa tie nts tak ing Eco naz ole 1% so lution . No. of patie nts 25 100% Fung us ide ntific ation prior to the rapy + cure d Afte r the rapy - 20 80% Fung us ide ntific ation Prior to the ra py + Afte r the rapy No sa mple - cure d ( cure ) 4 16% Fungus ide ntification prior to the rapy+ Afte r the ra py + not cure d 1 4% Ir aq i J.Pharm.Sc i., Vol.15 (1 ) ,2006 66 Table –6 Micro scopica lly res ults o f 52 patie nts ta king Pe varyl as refre nce . Therapeutic Re sults In Chronic Case s: 12 patients o f 52 p atie nts who s uffere d from chro nic myco sis ( dura tion 1 -5 years ) we re trea ted prep ared fo rmula of e co nazole the d ata that 1 1 p atie nts ( 9 1.7 ) we re cure d a fter trea tment with a verage d uratio n o f (2-16) wee ks and o nly one pa tie nt (8.3 ) wa s not re sp ond a s shown in table7 . Ta ble – 7 The ra pe utic results in 12 patie nts with c hronic myc os is la sting fo r more than one ye ar. The app earance of any s id e effe ct a fter the trea tme nt with b oth formulas wa s als o monitored burning and pruritrs (11,12,13,14,15 ) were obs erve d in only 3 p atie nts tre ated with eco na zole 1% so lutio n (o ut o f 52 p atients CONCLUSION The re sults of this c linica l inv es tiga tion clearly indica te d that the prep ared o f ec ona zo le nitrate 1% wa s effe ctiv e as c omp ared to that of commercial b ra nd Pe varyl®. No. of patie nts 2 5 100% Fungus ide ntification pr io r to the rapy + Afte r the ra py - c ure d 1 9 76% Fungus ide ntification Prio r to the rapy + Afte r the rapy cure d No sa mple - ( cure ) 5 20% Fungus ide ntification pr io r to the rapy + Afte r the ra py + no t c ure d 1 4 % Pa t. No Duratio n of dise ase in months Duration of tre atme nt in weeks Cure d No t cure d 1 2 3 4 5 6 7 8 9 10 11 12 12 12 14 24 13 12 60 16 14 12 12 30 2 1 1 2 2 3 .5 2 14.5 1 6 2 9 2 5 .5 + + + + + + + + + + + 12 pat. 1- 5 yea rs 2- 16 we eks 11 pat. 95% 1 pa t. 8.3% Ir aq i J.Pharm.Sc i., Vol.15 (1 ) ,2006 67 REFERENCES 1- Britis h Pha rma copoeia . Typo grao hy b y Majesties sta tionary a offic e , Lo ndo n , Camb rd ge2 001, Vo l.1 ,245. 2- Clark’s. is olation a nd identification of drug, 2nd.Ed . the pharmace utical press;Londo n; 19 86, 579 . 3- Hta ntsc hke , D.. In vitro sensitiv ity te st with antinycotic imido zo lc De riva tives and ava luation of re sults. Myko se n, 1 97 8,Sup pl I, 222 -9 . 4- Sc holar-M; P re diel—H; Korting—I- IC, Light and Ele ctio n Mic roscopic finding in a mode l of Hu man Coe tane ous Cand id ac ies, Journal o f Drug Ta rgeting, 1 99 9, 6(5) 36 1- 372 . 5- Sa min, L, H., Formula tion o f Ec onazo le nitrate as a to pical solution, Ira qi Journa l of Pha rma ce utic al Science s, 200 5,14, 20 - 30. 6- Le fler —F; Stev ens -DA, inhibition and killing of candida in Vitro by five imid azo le in clinica l use . Anti mic ro b — Agents — che mothe r (Antimicrobial-Agents -a nd- che mothe ra py), 1984, 25(Apr), 450 -454. 7- Culle n — S I; Rex- IH; Thorne — EG, comp arison of a new antifungal a gent, I perce nt Eco nazole nitra te (specsa zo le ) crea m versus I pe rc ent clotrEmazole cream in the trea tme nt o f i ntertrigi nous ca ndidosis, Curr- The r-Res (Current — Therap utic -Research); 198 4, 35 (Apr), 606 -6 09. 8- Stock-R, How effective is antimyc otic d rug? , pha rm-Int: 19 81, 2(Oct), 23 2-236 . 9- F redrikson-T, Trea tment of d crmatomyco ses with topical Fconazole and Clo trimazo le , e urr-The r-Res-Clin-Exp; 1979 , 2 5 (Ma y), 596-594. 10- Ve rma -BS , Eco nazole cream in fungal infe ctio n o f the s kin CurrF her—Res-Clin- Exp, 1978, 24(Nov ), 745-752 . 11- Schaller — M; P re idel-H; Janus chke-E; Korting-HC, Li ght and e lectron microscop ic findings in a mode l of hu man cuta ne ous candiois.J-Drug-Ta rget (Journal-o f-Drug- Targeting), 1999, 6 (5 ), 361 -3 72. 12- Ode h-F; Fa hry — H; K uhlwein-A; Nolting —S; S arta ni-A; et-a l. Doub le-b lind c linic al trail with a single d aily app lica tion o f entico na zole , Curr-Ther-Rcs (Curre nt — Theraputic-Res ea rc h), 1990, 47 (Ja n), 2 2-31. 13- Romague ra -C; He rrero-E; Ma rquez-M; Torres-J; Ortiz-J A, s tudy on the s ens itizing capac ity o f the ne w ataimyc otic sertacona zo le in the trea tme nt o f cuta ne ous mycoses, Arzeneim-Eorsc h (Arzneimitte l- F orsc hurg), 1 992 , 4 2 (5 S upp l), 754-756. 14- Pigatto -P ; Colli-E; Scatigna -M; Finzi-A. Evaluatio n o f s kin irritatio n a nd c onta ct sensitizing potential of fcnticonazole. Arzneim-Forsc h Arzneimittel-Forsc hurg), 1 99 0,40(3), 329-33 1. 15- Te tt-SE. To pical imidazoles . Aust-J- p ha rm (Australia n- Jo urnal- 0ft Pha rma cy), 1 98 6,67 (Fun), 567 -5 69.