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Formulation and Evaluation of Optimized Clotrimazole
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British Journal of Pharmaceutical Research 4 9 1014 1030 2014. low level was the formula of choice since it showed the highest drug release and the. highest antifungal activity, Keywords Clotrimazole emulgel multifactorial design antifungal activity. 1 INTRODUCTION, Topical formulations apply a wide spectrum of preparations both cosmetic and. dermatological to healthy or diseased skin 1 These formulations range in consistency from. solid through semisolid to liquids, When gels and emulsions are used in a combined form the dosage forms are referred to. emulgel 2 3 As the name suggests they are the combination of emulsion microemulsion. Novel polymers with complex functions as emulsifiers and thickeners have been widely used. due to their gelling capacity which allows the formulation of stable emulsion by decreasing. surface and interfacial tension and also by increasing the viscosity of the aqueous phase. Oil water and water oil emulsions are used as vehicles to deliver various drugs to the skin. 4 Emulsion gels are gaining importance due to many reasons they have better application. property in comparison to classical formulation as creams and ointment they have faster. and more complete release of the drug from the vehicle to the skin also they are convenient. to apply on hairy skin due to the absence of greasiness and lack of residue upon application. They permit the incorporation of both aqueous and oleaginous ingredients so hydrophobic. or poorly water soluble drugs as antifungal agents are easily incorporated in such type of. vehicles through the proper choice of the oily phase 5. Clotrimazole is an antifungal agent which inhibits the growth of pathogenic dermatophytes It. shares with econazole miconazole first choice status for topical treatment of tinea pedis. tineacruris and tineacorporis due to Candida albicans It is effective for topical treatment of. vulvovaginal and oropharyngeal candidiasis 6 7 8 For skin care and the topical treatment. of dermatological diseases a wide choice of vehicles including solid semisolids and liquid. preparations is available to physician and patients Within the major groups of semisolid. preparations the use of transparent emulgels has expanded both in cosmetics and. pharmaceuticals Emulgel or gellified emulsion is stable one and better vehicle for. hydrophobic or water insoluble drugs as Clotrimazole Also emulgels have a high patient. acceptability since they possess the advantages of both emulsions and gels Therefore they. have been recently used as vehicles to deliver various drugs to the skin. 2 MATERIALS AND METHODOLOGY,2 1 Materials, Clotrimazole was kindly provided by Alexandria Co for pharmaceutical and chemical. industries Alexandria Egypt carbpol 934 Goodrich Chemicals Co Cleveland Ohio. Hydroxylpropyl methyl cellulose HPMC 2910 was kindly supplied by Sedico for. pharmaceuticals Giza Egypt Tween 20 span 20 methyl and propyl parabens light liquid. paraffin propylene glycol Dimethyl Formamide DMF hydrochloric acid and ethyl alcohol. were purchased from Al Nasr pharmaceutical chemicals Cairo Egypt Triethanolamine. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. TEA was supplied from Morgan Chemicals Ind Co Cairo Egypt Canesten cream. Clotrimazole 1 B N 211030 was purchased from an Egyptian community pharmacy. Manufactured by Memfis for pharmaceuticals Cellulose membrane M Wt cutoff 10 000. 14 1000 was supplied from Sigma Chemical Company Saint Louis MO C albicans ATCC. No 10231was kindly provided by the Department of Microbiology October University for. Science and Modern Arts MSA clinical isolate growth at 25 C for 24 hours on Sabouraud s. 2 2 Methodology,2 2 1 Preparation of emulgel, The detailed composition for the prepared emulgel formulations is given in Table 1 The gel.
in formulations F1 F3 F5 and F7 was prepared by dispersing cabopol 934 in purified water. with continuous stirring using overhead stirrer for 5 min at 2000 rpm The gel in formulations. F2 F4 F6 and F8 was prepared by dispersing HPMC in hot purified water 70 C the gel. was cooled and left overnight The oil phase of the emulsion was prepared by dissolving. span 20 in light liquid paraffin while the aqueous phase was prepared by dissolving Tween. 20 in purified water Methyl and propyl parabens were dissolved in propylene glycol while. Clotrimazole was dissolved in ethanol both were then mixed with the aqueous phase The. aqueous and the oily phases were separately heated to 70 C and then the oily phase was. added to the aqueous phase with continuous stirring till cooled to room temperature The. emulsion and the gel were both mixed together in equal ratio with gentle stirring till obtaining. the emulgel 9 10, Table 1 Composition and codes of clotrimazole emulgel formulations W W. Components Formula s code,F1 F2 F3 F4 F5 F6 F7 F8,Clotrimazole 1 1 1 1 1 1 1 1. Carbopol 934 1 1 1 1,HPMC2910 2 5 2 5 2 5 2 5,Liquid paraffin 5 5 7 5 7 5 5 5 7 5 7 5. Tween20 0 6 0 6 0 6 0 6 1 1 1 1,Span20 0 9 0 9 0 9 0 9 1 5 1 5 1 5 1 5. Propylene glycol 5 5 5 5 5 5 5 5,Ethanol 2 5 2 5 2 5 2 5 2 5 2 5 2 5 2 5.
Methyl paraben 0 03 0 03 0 03 0 03 0 03 0 03 0 03 0 03. Propyl paraben 0 01 0 01 0 01 0 01 0 01 0 01 0 01 0 01. Purified water to 100 100 100 100 100 100 100 100,HPMC Hydroxypropyl methyl cellulose. 2 2 2 Experimental design and statistical analysis. A 3 factor 2 level factorial design was used to explore response surfaces and constructing. second order polynomial models with Statgraphic plus software Version 4 1 The 2 level. factorial design was specifically selected since it requires fewer runs than other experimental. designs The nonlinear computer generated quadratic model is given as. Y 0 1 X1 2 X2 3 X3 12 X1X2, British Journal of Pharmaceutical Research 4 9 1014 1030 2014. 13 X1X3 23 X2X3 123 X1X2X3, Where Y is the measured response associated with each factor level combination 0 is an. intercept 0 to 123 are regression coefficients computed from the observed experimental. values of Y X1 X2 and X3 are the coded levels of independent variables The terms X1 X2. and X3 i 1 2 or 3 represent the interaction and quadric terms respectively 2 level design. where selected each variable is tested at a low 1 and high 1 level 11. Eight Clotrimazole emulgel formulations were prepared according to 2 full factorial designs. to optimize the formulation factors and evaluate the main effects The independent variables. were the type of gelling agent X1 liquid paraffin X2 and emulsifying agent X3 The. two levels of gelling agent type were used carpobol and HPMC denoted the value 1 and. 1 in the above design respectively, Two levels of liquid paraffin concentration were chosen to be 5 and 7 5 denoted 1 and 1. respectively Finally the emulsifying agent concentration were 1 5 and 2 5 denoted 1 and. 1 respectively The eight experimental trials and the respective observed responses are. given in Table 2, Table 2 Variablesand observed response in 2 factorial designfor emulgel.
formulations, Formulations Independent variables Dependent variables. X1 X2 X3 Y1 Y2,F1 1 1 1 29 55 38 5,F2 1 1 1 32 81 43 4. F3 1 1 1 27 46 32 2,F4 1 1 1 28 68 35 7,F5 1 1 1 38 58 48 5. F6 1 1 1 43 22 57 5,F7 1 1 1 30 47 40 6,F8 1 1 1 35 33 46 7. X1 Gelling agent 1 Carbopol 1 hydroxpropylmethyl cellulose HPMC. X2 Liquid paraffin 1 5 1 7 5 Y1 Drug release after 3 hrs Y2 antifungal activity. X3 Emulsifying agent 1 1 5 1 2 5,2 2 3 Evaluation of emulgel.
2 2 3 1 Physical appearance and pH determination, The prepared Clotrimazole emulgel were inspected visually for their color homogeneity. consistency and pH The pH values of 1 aqueous solutions of the prepared emulgels were. measured by a pH meter Orion Research Inc USA 12 Experiments were carried out in. triplicates,2 2 3 2 Drug content determination, The drug content of Clotrimazole emulgel was measured by dissolving a known weight of the. emulgel formulation one gram in 100 ml methanol appropriate dilutions were made and the. resulting solution was then filtering using millipore filter 0 45 m Absorbance was. measured at 260 nm using UV spectrophotometer Shimadzu UV 1700 Japan 11 Drug. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. content was calculated using the slope and the intercept obtained by linear regression. analysis of standard calibration curve Experiments were carried out in triplicates. 2 2 3 3 Rheological studies, The viscosity of different Clotrimazole emulgel formulations was determined at 25 C using a. cone plate viscometer with spindle 52 Brookfield model HBDV III USA 13 Experiments. were carried out in triplicates By applying Ostwald de Waele relationship power law fluid. the flow behavior index n can be calculated By n 1 the Ostwald de Waele relationship. describes Newtonian behavior For n 1 Pseudoplastic fluids and for n 1 Dilatant behavior. can be described, Where Shear stress Pa Flow consistency index Pa sn Shear rate s 1 Flow. behavior index,2 2 3 4 In Vitro release studies, The study was carried out using the modified USP apparatus type II Hanson SR8 plus 80.
USA Two grams of each emulgel was spread on the cellophane membrane previously. soaked overnight in the dissolution medium The loaded membrane was stretched over a. glass cup of diameter 3 cm and then the cup was immersed in 100 ml of the dissolution. medium 25 v v DMF in 0 02N HCl to maintain sink condition the temperature was. maintained at 37 0 5 C with paddle agitation speed 50 rpm An aliquot of 5 ml was. withdrawn at different intervals of time The withdrawn samples were replaced by equal. volumes of fresh release medium The samples were assayed spectrophotometry at. max260 nm using ultraviolet spectrophotometer Experiments were carried out in triplicates. The effect of gelling type the liquid paraffin concentration and emulsifying agent. concentration was studied 5,2 2 3 5 Kinetic analysis of the drug release. Kinetic analysis of the data was carried out to determine the release model which describes. the proper order of drug release as follow Zero order cumulative drug release vs time. first order log cumulative drug retained vs time and Higuchi model cumulative drug. retained vs square root of time 14 15 16,2 2 3 6 Antifungal activity studies. The prepared emulgel formulations were tested against candida albican strain ATCC No. 10231 using agar cup method Cups of 10mm diameter were made aseptically in sabouraud. dextrose agar after being inoculated with the tested fungal suspension strain 10 cfu ml by. spreading on the agar surface The cups were filled with each prepared formulation by sterile. syringe The zone of inhibition of each cup was observed and the radius of the zone of. inhibition was measured and compared to the control canestin cream 17 Experiments were. carried out in triplicates, British Journal of Pharmaceutical Research 4 9 1014 1030 2014. 2 2 3 7 Stability studies, The prepared Clotrimazole emulgels were packed in aluminum tubes 5 grams and. subjected to stability studies at 25 C 60 relative humidity RH and 40 C 75 RH for a. period of 3 months Samples were withdrawn at time intervals of 15 days and evaluated for. physical appearance pH rheological properties drug content and drug release 18. 3 RESULTS AND DISCUSSION,3 1 Physical Appearance and pH Determination.
The prepared Clotrimazole emulgel formulations were inspected visually for color. homogeneity phase separation consistency and pH All formulations showed white color. formulations prepared using carbopol 934 as gelling agent showed glossy appearance No. phase separation was noticed formulations showed suitable homogeneity and consistency. The pH of the emulgel formulation was in the range of 5 66 6 53 which considered. acceptable to avoid the risk of skin irritation upon application to skin 19 20 Results are. shown in Table 3and Fig 1,6 5 6 38 6 33 6 35 6 39,pH of Formulation. F1 F2 F3 F4 F5 F6 F7 F8,Formulation,Fig 1 pH of emulgel formulation F1 F8. 3 1 Drug Content, Results of drug content are shown in Table 3 and represented in Fig 2 The drug content of. different emulgel formulations was estimated and the results were in official limits with range. of 95 55 to 98 45 mg which indicate uniform distribution of the drug throughout the. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Table 3 Physical appearance pH and drug content of clotrimazole emulgel. formulations, Formulations Color Phase Homogeneity Consistency pH Drug. Separation content,F1 Shiny white None 6 13 95 55,F2 White Shiny None 6 38 96 34.
F3 white None 6 33 98 21,F4 White None 6 13 98 09,F5 Shiny white None 6 53 96 84. F6 White None 6 35 96 39,F7 Shiny white None 5 66 97 44. F8 White None 6 39 98 45, Excellent Good Satisfactory All parameters are inspected visually. 98 21 98 09 97 44,98 96 84 96 39,Drug Content,F1 F2 F3 F4 F5 F6 F7 F8. Formulation, Fig 2 Drug content mg of emulgel formulation F1 F8.
3 1 Rheological Studies, Viscosities of different Clotrimazole emulgel formulations at both low and high shear rates. are shown in Table 4 the results showed that the emulgel formulations prepared using. carbopol 934 as gelling agent F1 F3 F5 and F7 possessed higher viscosities than emulgel. formulations prepared using HPMC 2910 F2 F4 F6 and F8 This is due to the difference in. the type of gelling agent which results in changing the structure consistency 21 this effect. may be due to the higher hygroscopicity of HPMC compared with carbopol 934 22 Figs 3. 4 and 5 show the rheograms of Clotrimazole emulgel containing carbopol HPMC and the. market product canesten cream As represented in the Figures all the prepared emulgel. exhibited a shear thinning behavior as the viscosity decreased by increasing the shear rate. The figures also show that all Clotrimazole emulgel formulations possessed thixotropic. behavior where the down curve was displaced with regard to the up curve at any rate of. shear on the down curve a lower shear stress than it had on the up curve a hysteresis loop. was formed between the up curve and the down curve By applying Ostwald de Waele. equation the flow behavior index n for all formulation was found to be less than 1. indicating pseudoplastic behavior Thixotropy time dependent flow needs a definite time to. rebuild its original structure that breaks down during continuous shear measurements 23. The results of Clotrimazole emulgel are in agreement with Abd El Bary et al who had. prepared Chloramphenicol emulgel using Carbopol 940 as a gelling agent 24. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. 8000 F1 8000 F3,Shear Stress dyne cm2,Shear Stress. 2000 2000 Up Curve,Down Curve,Down Curve,50 75 100 150 200 250 50 75 100 150 200 250. Shear Rate 1 sec ShearRate 1 sec,8000 8000 F7,Shear Stress dyne cm2. Shear Stress dyne cm2,Up Curve Up Curve,Down Curve 2000.
50 75 100 150 200 250,50 75 100 150 200 250,Shear Rate 1 sec Shear Rate 1 sec. Fig 3 Rheograms of Carbopol 934 Emulgel F1 F3 F5 and F7. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Down Curve,Shear Stress,50 75 100 150 200 250,ShearRate 1 sec. Fig 4 Rheogram of the Market Product Canesten Cream. Table 4 Viscosities cp of Clotrimazole emulgel formulationsat low and high rateof shear. Formulations min max Formulations min max,F1 1926 180 F2 1365 1162. F3 4062 7255 F4 817 743,F5 3894 1502 F6 800 666,F7 3145 1321 F8 1027 841. Canesten 1152 606,Viscosity at low rate of shear,Viscosity at high rate of shear.
British Journal of Pharmaceutical Research 4 9 1014 1030 2014. F2 8000 F4,Shear Stress dyne cn2,Shear Stress dyne cm2. 2000 Up Curve 2000 Up Curve,Down Curve Down Curve,50 75 100 150 200 250 50 75 100 150 200 250. ShearRate 1 sec,ShearRate 1 sec,8000 F6 8000 F8,Shear Stress dyne cn2. Shear Stress dyne cn2,2000 Up Curve 2000 Up Curve,Down Curve. Down Curve,50 75 100 150 200 250 50 75 100 150 200 250.
Shear Rate 1 sec Shear Rate 1 sec, Fig 5 Rheograms of HPMC 2910 Emulgel F2 F4 F6 and F8. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. 3 4 In vitro drug release, The in vitro release of Clotrimazole from different emulgel formulations and the market. product at 37 C was investigated and the results are represented in Fig 6 It was noticed. that the release of emulgel formulations are higher than that of canesten cream the market. product The release of Clotrimazole from its emulgel can be ranked in the following. descending order F6 F5 F8 F2 F7 F1 F4 F3 where the amount of drug release. after 3 hours was found to be 43 22 38 58 35 33 32 81 30 47 29 55 28 66. and 27 46 respectively While the release of Clotrimazole from the canesten cream after 3. hours was found to be 25 32,Drug released,10 20 30 40 50 60 90 120 150 180. Time intervals minutes, Fig 6 Release profiles of Clotrimazole from its emulgel formulations. Formulations F6 and F5 were observed to have the highest release this was due to the. presence of liquid paraffin and emulsifying agent in low and high level respectively These. results were due to the increase of hydrophilicity of emulgel which facilitate the penetration. of the release medium into the emulgel and the diffusion of the drug fromemulgel The. results of Clotrimazole emulgel are in agreement with Abd El Bary et al 24 who showed. that the presence of liquid paraffin led to retardation of Chloramphenicol release from its. emulgel formulation, The release of drug from formulation F5 was found to be lower than the release from F6 this.
may be due to the higher viscosity of Carbopol emulgel formulation as observed in Table 4. 25 In contrary to F6 and F5 formulations F4 and F3 showed the lowest drug release this. may be due to the presence of liquid paraffin and emulsifying agent in high and low level. respectively F8 has both liquid paraffin and the emulsifying agent in their high levels and. exhibited higher release than F2 formulation containing both liquid paraffin and the. emulsifying agent in their low levels The previous result indicated that the effect of. emulsifying agent in high level on the drug release was more pronounced than the effect of. liquid paraffin in low level on the drug release, British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Although F5 has Carbopol as gelling agent it showed higher drug release than F8 which has. HPMC as a gelling agent This result is due to that F5 has liquid paraffin in low level while F8. has liquid paraffin in high level The same explanation was found when comparing F1 and. F4 formulations These results showed that the effect of liquid paraffin in decreasing the drug. release from emulgel formulation was more than the effect of HPMC on the drug release. Thus we can arrange the studied factors according to their effect on drug release from the. emulgel formulation as follows The emulsifying agent concentration the liquid paraffin. concentration the gelling agent type,3 5 Kinetic Analysis of the Drug Release. The release data analysis was carried out using the various kinetic modules using. cumulative release vs time zero order kinetic model log cumulative drug remained. vs Time first order kinetic model and cumulative drug release vs square root of time. Higuchi model 26 27 28 The correlation coefficient R2 values are tabulated in Table 5. Most of the formulation showed first order release except formulations F3 and F7 which. showed zero order kinetics and diffusion model kinetic respectively This may be due to the. presence of carbopol 934 as a gelling agent and liquid paraffin in its higher level in both F3. Table 5 The kinetic study of the In vitro release data of Clotrimazole from is different. emulgel formulations,Formulation Correlation Coefficient R2. Zero Order First Order Diffusion,F1 0 98881 0 98896 0 97038. F2 0 98940 0 98973 0 97737,F3 0 99213 0 99109 0 97190.
F4 0 99125 0 99181 0 97338,F5 0 98619 0 98851 0 97951. F6 0 99050 0 99270 0 98951,F7 0 98458 0 98935 0 99076. F8 0 98613 0 98851 0 97957,Canesten cream 0 99144 0 99376 0 98835. 3 6 Antifungal Activity Studies, The antifungal activity of Clotrimazole from its different emulgel formulations as well as in its. market available cream form Canesten cream are shown in Table 6 and Fig 7 The zone. of inhibition was taken as a measure of the drug antifungal activity The greatest activity was. observed with F6 where the zone of inhibition was 57 5mm while the lowest activity was. found with F3 where the zone of inhibition was 30mm These results were due to the. increase of hydrophilicity of emulgel in F6 which facilitate the penetration of the release. medium into the emulgel and the diffusion of the drug from emulgel The results are in. agreement with the results obtained from the in vitro release study which indicates good. correlation between the in vitro and the antifungal activity studies. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Table 6 The inhibition zone as a criterion for Clotrimazole antifungal activity in its. different emulgel formulations, Formulation Inhibition Zone Formulation Inhibition Zone.
mm SD mm SD,F1 38 5 0 56 F5 48 5 0 82,F2 43 4 1 08 F6 57 5 1 17. F3 32 2 0 84 F7 40 6 0 96,F4 35 7 0 75 F8 46 7 0 76. Canesten cream 28 5 0 69,The inhibition zone is average of n 3. Zone of inhibition mm,50 43 4 46 7,40 32 2 35 7,F1 F2 F3 F4 F5 F6 F7 F8 Canesten. Clotrimazol emulgel formulations, Fig 7 Zone of inhibition of Clotrimazole emulgel formulations.
3 7 Stability studies, The prepared Clotrimazole emulgel formulations were found to be stable after subjected to. stability studies at 25 C 60 relative humidity RH and 40 C 75 RH for a period of 3. months No significant change was noticed in the parameters evaluated for physical. appearance pH rheological properties drug content drug release and antifungal activity. 3 8 Multifactorial Design, 2 full factorial designs to optimize the formulation factors and evaluate the main effects were. used The independent variables were the type of gelling agent X1 liquid paraffin X2. and emulsifying agent X3 Two levels of gelling agent type were used carpobol and. HPMC denoted the value 1 and 1in the above design respectively. Two levels of liquid paraffin concentrations were chosen to be 5 and 7 5 denoted 1 and. 1 respectively Finally the emulsifying agent concentrations were 1 5 and 2 5 denoted 1. and 1 respectively, Three dimensional 3D plots and standard pareto chart for the drug release Y1 and. antifungal activity Y2 were drawn using Statgraphics plus design software version 4 1 is. shown in Figs 8 and 9 respectively, British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Estimated Response Surface,emulsifying agent conc 0 0.
Desirability,0 39 0 20 6,Liquid paraffin conc,Gelling agent type. Standardized Pareto Chart for Drug release after 3 hrs. C emulsifying agent conc,B Liquid paraffin conc block. A Gelling agent type,AB AC block,Standardized effect. Fig 8 a Response surface plot and Fig 8 b standard pareto chart showing the. effect of X1 X2 and X3 on the drug release after 3 hrs Y1. Estimated Response Surface,emulsifying agent conc 0 0. Desirability,1 0 6 0 2 1,0 6 Liquid paraffin conc,Gelling agent type.
Standardized Pareto Chart for Antifungal activity,C emulsifying agent conc. B Liquid paraffin conc block,A Gelling agent type,AB AC block. 0 2 4 6 8 10,Standardized effect, Fig 9 a Response surface plot and Fig 9 b standard pareto chart showing. the effect of X1 X2 and X3 on the antifungal activity Y2. X1 Gelling agent type X2 Liquid paraffin X3 Emulsifying agent. British Journal of Pharmaceutical Research 4 9 1014 1030 2014. Regression analysis of the data was carried out in statistical analysis system SAS by a. special cubic model From ANOV Astudy on the data of Clotrimazole release after 3 hours. Y1 and the antifungal activity Y2 which is shown in Table 7 the standard error was below. 5 indicating that the observed responses were very close to predicted values The Durbin. Watson DW statistic tests the residual to determine if there is any significant correlation. between data since the DW value is greater than 1 4 there is probably not any serious. autocorrelation in the residuals, Table 7 Summary of results of regression analysis for responses Y1 drug release. after 3 hrs and Y2 antifungal activity,Response R Adjusted R Standard Mean Durbin.
error absolute Watson,error statistic, Drug release after 3 hrs Y1 98 18 93 62 1 37 0 627 1 7099. Antifungal activity Y2 98 69 95 41 1 71 0 837 2 23. The promising Formulation was selected on the basis of the accepted criteria of both the. drug release after 3hrs and the drug antifungal activity From the obtained results. Hydroxypropyl methyl cellulose as a gelling base was used in addition to liquid paraffin in its. low level 5 and emulsifying agent in its high level 7 5 These criteria were found in. formulation F6 as the observed values were very close to the predicted ones as shown in. Table 8 Observed and predicted values of the responses for the optimized. Clotrimazole formulation F6,Response Observed value Predicted value Residual. Drug release after 3 hrs Y1 43 22 42 87 0 35,Antifungal activity Y2 57 5 56 4 1 1. 4 CONCLUSION, From the above results we can conclude that emulgel will be a solution for incorporating. hydrophobic drugs in water soluble gel bases Clotrimazole emulgel formulations prepared. using either carbopol 934 or HPMC 2910 showed acceptable physical properties pH drug. content viscosity and antifungal activity stability studies revealed no significant differences. before and after storage for the selected formula The study also shows that the use of. 2 factorial designs are valid in predicting the optimized formulation which was found to be. HPMC based emulgel with liquid paraffin in its low level and emulsifying agent in its high. level since it shows the highest drug release and antifungal activity.


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