US 2011 (0281830A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0281830 A1 Sulur et al. (43) Pub. Date: Nov. 17, 2011

(54) NOVEL DERMACEUTICAL CREAM MADE (30) Foreign Application Priority Data USING SODIUM FUSDATE AND Jan. 21, 2009 (IN) ...... 134/MUMA2009 (75) Inventors: Vanangamudi Subramaniam Publication Classification Sulur,r Chennai (IN);: Madhavan (51) Int. Cl. Srinivasan, Chennai (IN); A 6LX 3/575 (2006.01) Neelakandan Narayanan Chulliel, A6IP3L/00 (2006.01) Chennai (IN); Haridas Sankar, A6IP 29/00 (2006.01) Mumbai (IN). Kausik Ghosh, A6IP 700 (2006.01) Chennai (IN) (52) U.S. Cl...... S14/17O (73) Assignee: APEX LABORATORIES (57) ABSTRACT PRIVATE LIMITED, CHENNAI, The invention discloses a dermaceutical cream containing TN (IN) steroids and an antibacterial agent in the form of Fusidic acid, which Fusidic acid is formed in situ from Sodium Fusidate as the starting raw material, wherein Sodium Fusidate is con (21) Appl. No.: 13/144.932 verted into Fusidic acid under oxygen-free environment. The cream of the present invention has greater shelf-life stability (22) PCT Filed: Jan. 20, 2010 and the finer particle size of the API than the conventional creams containing Fusidic acid. The cream of the present (86). PCT No.: PCT/B2O1O/OSO242 invention contains Fusidic acid as the API that has been formed in situ from Sodium Fusidate, and steroids in a cream S371 (c)(1), base comprising an acid, a co-solvent, an emulsifier and a (2), (4) Date: Jul.18, 2011 waxy material along with water, preferably purified water. US 2011/028 1830 A1 Nov. 17, 2011

NOVELDERMACEUTICAL CREAM MADE of ointment rather than cream. Drawbacks of ointments over USING SODIUM FUSDATE AND STEROIDS creams are well known and it's generally preferable to use creams rather than ointments for topical application. FIELD OF INVENTION 0008. Several aspects of Fusidic acid as an API are known: 0009. It is thermolabile 0001. The present invention relates to primary & second 0010. It is available in cream formulations ary bacterial skin infections and inflammations and in par 0011. It can be obtained from Sodium Fusidate by dis ticular it relates to the single dose treatment using a steroids Solving the latter in an aqueous phase and adding acid to cream that also contains an antibacterial agent in the form of the solution, whereby Fusidic acid precipitates. How a Fusidic acid wherein the Fusidic acid has been made using ever, the Fusidic acid precipitate is difficult to process Sodium Fusidate as the starting Active Pharmaceutical Ingre into a cream form first due to its coarse and uneven dient (API). particle size and second retrieving Fusidic acid from wet cake involves drying and further handling which dete BACKGROUND OF THE INVENTION riorates the Fusidic acid due to exposure to oxygen 0002. Use of steroids to alleviate inflammation, irritation 0012. The stability of the API in a Fusidic acid cream is and itching caused by skin ailments is well known. It is also unreliable due to the thermolabile nature of Fusidic acid well known that use of Steroids compromises patient's 0013 Stabilization of medicaments containing Fusidic immune system and exposes them to bacterial infections. acid against oxidation involves observing a number of Strin Single dose therapies containing steroids and antibacterials gent precautionary procedures during manufacture and stor are well known. age. These include: 0003) Numerous single dose treatments, both topical and 0014 replacing Oxygen in pharmaceutical containers systemic, are currently employed for the treatment of above with inert gases such as Nitrogen, Carbon dioxide, skin inflammations. Topical and systemic inflammatory treat Helium and the like ment compositions typically employ a combination of corti 0.015 avoiding contact of the medicament with heavy costeroids in a base component. The active ingredients typi metal ions which catalyze oxidation, cally comprise Such as steroids like 0016 storing the API at reduced temperatures through Valerate, , Mometa out its shelf life before processing Sone Furoate, Acetate, 0017. In practice this means stricter controls during the Acetate, Propionate. Beclomethasone Dipropi manufacture as well as storage of such API (storing it typi onate, Betamethasone Dipropionate and the like. cally at 2°C. to 8°C. in air-tight containers throughout their 0004 Numerous treatments, both topical and systemic, shelf life). are available for the primary and secondary skin infection 0018. There is therefore a need to provide a Fusidic acid caused by sensitive Gram-ve organisms such as Staphylo cream in which Fusidic acid will be of greater stability at the coccus aureus, Streptococcus spp etc. Topical and systemic time of the manufacture of the cream, and which will sustain bacterial infection treatment compositions typically employ its stability at an acceptable level throughout its shelf life. at least one active pharmaceutical ingredient (API) in com 0019. There's a need to provide dermaceutical cream con bination with a base component. In the cream form, the APIs taining steroids, and an antibacterial in the form of Fusidic typically comprise an antibiotic/antibacterial Such as Fusidic acid, and in which Fusidic acid will be of greater stability at acid and the like. the time of the manufacture of the cream, and which will 0005. In the currently available Fusidic acid creams, sustain its stability at an acceptable level throughout its shelf Fusidic acid in fine powder form is used as source API. The life. Small particle size enhances its dermal contact by providing a large specific Surface area and penetration, and provides a OBJECTS AND ADVANTAGES OF THE Smooth feel on application to skin. However, a serious short INVENTION coming of the fine size of Fusidic acid particles is that it 0020. It is therefore one object of the present invention to presents an enormous Surface area for contact and reaction provide a cream which contains Fusidic acid as the active API with molecular Oxygen during manufacture, handling, and but which has greater stability of the API throughout its shelf processing of the cream. This has serious implications to its life. chemical stability and results in rapid reduction in potency of the API (Fusidic acid) in the final cream formulation. Degra 0021. It is a further objective of the present invention to dation due to oxidation is a major cause of instability of provide a dermaceutical cream containing at least one , currently available Fusidic acid creams. Table 1 show that the and an antibacterial agent in the form of Fusidic acid, in which degradation in the API samples (Fusidic acid) exposed to Fusidic acid will be of greater stability at the time of the oxygen ranged between 7.7% and 11% for conditions ranging manufacture of the cream, and which will sustain its stability from room temperature to 45° C. when analysed at three at an acceptable level throughout its shelf life. months of exposure period at the above conditions. 0006. It is known that greater the exposure time of Fusidic BRIEF SUMMARY OF THE INVENTION acid as the raw API to Oxygen, greater the limitations on 0022. The invention discloses a dermaceutical cream con stabilising Fusidic acid in a formulation. However, there is no taining steroids Such as Betamethasone Valerate, Fluticasone published data on the stability of Fusidic acid over a period of Propionate, Furoate, Dexamethasone Acetate, time. Hydrocortisone Acetate, , Beclom 0007 As an alternative to Fusidic acid, Sodium Fusidate is ethasone Dipropionate, Betamethasone Dipropionate and the known to have been used to make dermaceutical medica like, and an antibacterial agent in the form of Fusidic acid, ments for topical application. However, these are in the form which Fusidic acid is formed in situ from Sodium Fusidate as US 2011/028 1830 A1 Nov. 17, 2011

the starting raw material, wherein Sodium Fusidate is con verted into Fusidic acid under oxygen-free environment. The TABLE 1-continued cream of the present invention has greater shelf-life stability and the finer particle size of the API than the conventional Results Of3 Months Old Fusidic Acid (API) Analysis By Stability creams containing Fusidic acid. The cream of the present Indicating HPLC Method And Titration Method invention contains Fusidic acid as the API that has been Name of Sample: FUSIDIC ACID BP: formed in situ from Sodium Fusidate, and steroids such as Pack: Open (O) & Closed (C) Petri dish Betamethasone Valerate, Fluticasone Propionate, Mometa Fusicic Acid Percentage Sone Furoate, Dexamethasone Acetate, Hydrocortisone *In- Assay (% Drop (% Acetate, Clobetasol Propionate. Beclomethasone Dipropi onate, Betamethasone Dipropionate and the like in a cream tial Tiltra- Titra base comprising an acid, a co-solvent, an emulsifier and a S. No Conditions (%) tion HPLC tion HPLC Remarks waxy material along with water, preferably purified water. 3 45° C. (O) 98.52 89.52 2.08 11.08 After 3 4 45° C. (C) 99.10 92.12 150 8.48 Months DETAILED DESCRIPTION OF THE INVENTION 0023. We discussed earlier the known aspects of the topi cal preparations that have Fusidic acid and Sodium Fusidate as the APIs. It is evident from the current state of knowledge Stability Analysis of Sodium Fusidate that: 0032 0024 Creams containing Fusidic acid that are made using Sodium Fusidate as starting API are not available. 0025 Creams containing Fusidic acid that are made TABLE 2 using Sodium Fusidate along with steroids such as Results Of3 Months Old Sodium Fusidate (API) Analysis By Betamethasone Valerate, Fluticasone Propionate, Stability Indicating HPLC Method And Titration Method Mometasone Furoate, Dexamethasone Acetate, Hydro Name of the Sample: Sodium Fusidate BP Acetate, Clobetasol Propionate, Beclometha Pack: Open & Closed Petri dish Sone Dipropionate, Betamethasone Dipropionate and Sodium Fusidate Percentage the like as starting APIs are not available. *In- Assay (% % 0026. There is no published data on the stability of Sodium Fusidate as the API. tial Titra- Titra 0027 Sodium Fusidate is not considered to be inher S. No Conditions (%) tion HPLC tion HPLC Remarks ently more stable as an API than Fusidic acid. 1 RT (O) 98.7 97.71 96.25 O.99 2.45 API 0028. In the face of this, it has been surprisingly discov 2 RT (C) 98.85 97.67 –0.15 1.03 analysed ered that Sodium Fusidate as an API is significantly more 3 45° C. (O) 97.07 92.6S 1.63 6.05 After 3 stable than Fusidic acid and that Fusidic acid deteriorates 4 45° C. (C) 97.16 92.96 1.54 5.74 Months more rapidly than Sodium Fusidate. 0029. There is no published data on the stability of Sodium Fusidate as the API. The applicant carried out experiments on 0033. In both studies the * Initial denotes the results of the Sodium Fusidate to evaluate its stability. It can be seen from samples tested at the time of receipt of the API from the Table 2 that the degradation of Sodium Fusidate over a tem Supplier. perature range of room temperature to 45° C. ranged between 0034. It can be observed from Tables 1 and 2 that: 2.45% and 6%. 0035. In the case of Fusidic Acid, there is about 7.7% 0030 Tables 1 and 2 also show the comparison between loss in 3 Months at room temperature (open condition) the stability of the Fusidic acid and Sodium Fusidate as raw and about 11% loss in 3 Months at 45° C. (open condi APIs. The study was carried out using an in-house HPLC tion). method developed by the applicant, which the applicant 0036. In the case of Sodium Fusidate, there is about believes is a true stability-indicating method as opposed to the 2.5% loss in 3 Months at room temperature (open con titration method suggested in British Pharmacopoeia (BP). dition) and about 6% loss in 3 Months at 45° C. (open This is because the BP method does not differentiate between condition). the intact API and the degraded form. 0037. The data thus shows that Sodium Fusidate as an API is more stable than Fusidic acid. Stability Analysis of Fusidic Acid 0038. The applicant explored the possibility of making a 0.031 cream (rather than an ointment) using Sodium Fusidate (rather than Fusidic acid) and steroids such as Betamethasone TABLE 1. Valerate, Fluticasone Propionate, Mometasone Furoate, Dex Results Of3 Months Old Fusidic Acid (API) Analysis By Stability amethasone Acetate, Hydrocortisone Acetate, Clobetasol Indicating HPLC Method And Titration Method Propionate, Beclomethasone Dipropionate, Betamethasone Name of Sample: FUSIDIC ACID BP: Dipropionate and the like. Although Sodium Fusidate has Pack: Open (O) & Closed (C) Petri dish been used in dermaceutical applications, it has not been pos sible to make creams that use Sodium Fusidate. This is Fusicic Acid Percentage *In- ASSay (90 Drop (% because of the inherent alkalinity of Sodium Fusidate (pH 7.5 to 9), which means it cannot be used in a cream form therefore tial Tiltra- Titra all products manufactured using Sodium Fusidate as starting S. No Conditions (%) tion HPLC tion HPLC Remarks material are ointments. A dermaceutical cream that uses 1 RT (O) 100.6 99.21 92.93 1.39 7.67 API Sodium Fusidate and steroids would exploit the benefit of the 2 RT (C) 99.02 94.37 1.58 6.23 analysed fact that Sodium Fusidate is more stable than Fusidic acid and it would also provide a cream formulation which is far Supe US 2011/028 1830 A1 Nov. 17, 2011

rior in its application qualities than an ointment. It would thus 0046. The Fusidic acid and steroids cream of the present fill an existing need for a cream that has better stability than invention has been manufactured in a totally oxygen free currently available creams containing Fusidic acid and Ste environment under purging with inert gas and applying roids. vacuum. Under these conditions, the Sodium Fusidate is con 0039. The applicant therefore surprisingly discovered that verted in situ into Fusidic acid. The cream of the present in order to achieve greater stability of the API in a dermaceu invention is used in the treatment of bacterial skin infections tical cream, Sodium Fusidate rather than Fusidic acid may be and inflammations. used as the starting API during the cream's manufacture. 0047. The pH of the product of the present invention is from about 3 to 6. On the other hand, Sodium Fusidate oint Using Sodium Fusidate as starting material eliminates the ments that are commercially available are greasy and cos drawback associated with the manufacture and storage of metically non elegant. existing Fusidic acid creams. 0048. It is essential that the active drug penetrates the skin 0040. The applicant has also discovered that the Fusidic for the optimum bio-dermal efficacy. The particle size of the acid and Steroids cream prepared using Sodium Fusidate as active drug plays an important role here. It is necessary that the starting APIs showed good chemical stability, and effi the active drug is available in a finely dispersed form for the cacy, product to be being efficacious. Also this is to be achieved in 0041. The application discloses a cream containing Ste the safe pH compatible environment of skin (4.0 to 6.0). To roids such as Betamethasone Valerate, Fluticasone Propi achieve all these, it is essential to choose proper vehicles or onate, MometaSone Furoate, Dexamethasone Acetate, co-solvents for the dissolution or dispersion of the drug. Hydrocortisone Acetate, Clobetasol Propionate. Beclom 0049. The product of the present invention is efficacious ethasone Dipropionate, Betamethasone Dipropionate and the due to the pronounced anti-inflammatory, antibacterial activ like and Fusidic acid (the API) that has been prepared using ity of the steroids and regenerated Fusidic acid which is Sodium Fusidate as the starting API, in which Fusidic acid available in reduced particle size than the conventional prod forms in-situ under totally oxygen free environment by slow ucts, and in a finely dispersed form. addition of an acid, into a molecular dispersion form (due to 0050. The inventor has screened different co-solvents the presence of a co-solvent) at the intermediate stage, and such as Propylene Glycol, Hexylene Glycol, PolyEthyleneG which Fusidic acid regenerates as an extremely fine disper lycol-400 & the like and dissolved the Sodium Fusidate in one sion when added to a final cream base, thereby resulting in a of above co-solvents varying from about 5% (w/w) to 40% finely and homogeneously dispersed Fusidic acid in the final (w/w) under inert gas purging and under vacuum and con cream. All these operations are performed in an environment verted to Fusidic acid in-situ by adding an acid such as HCl, free of atmospheric oxygen. The cream of the present inven HSO, HNO, Lactic acid and the like from about 0.005% tion contains Fusidic acid as the API that has been formed in (w/w) to about 0.5% (w/w) under stirring and obtained situ from Sodium Fusidate, steroids such as Betamethasone Fusidic acid in more stabilized and solution form, which Valerate, Fluticasone Propionate, Mometasone Furoate, Dex makes our final product in a cream base which easily pen amethasone Acetate, Hydrocortisone Acetate, Clobetasol etrates the skin and highly efficacious, and also highly derma Propionate. Beclomethasone Dipropionate, Betamethasone compatible by having a pH of about 3.0 to about 6.0. Dipropionate and the like in a cream base comprising an acid, 0051. The stability of the product is confirmed by the a co-solvent, an emulsifier and a waxy material along with stability studies performed for 3/6 months as per ICH guide water, preferably purified water. lines. 0042. The APIs which may be employed in the present invention as starting APIs are either acid-based actives or Experimental Data their salts well known in the art of treating bacterial primary 0.052 APIs-stability experiments were carried out (see & secondary infections and inflammations. Examples of suit tables 3-20) using several products that are representative of able acid-based actives or their salts which may be used the present invention. Tests were carried out to observe (or include, but are not limited to Sodium Fusidate and steroids measure as appropriate) the physical appearance of the prod such as Betamethasone Valerate, Fluticasone Propionate, uct, the pH value and assay of the APIs over a period of time. Mometasone Furoate, Dexamethasone Acetate, Hydrocorti Each gram of product of the present invention used for the sone Acetate, Clobetasol Propionate. Beclomethasone Dipro tests contained Sodium Fusidate in the amount required to pionate. Betamethasone Dipropionate and the like. produce 2% (w/w) Fusidic acid in the finished product and 0043. These acid-based active compounds or their salts appropriate amount of steroids as mentioned below require a base component to be used in the pharmaceutical 0053 i. Betamethasone Valerate 0.12% (w/w) composition that uses the compounds, since the compounds 0054 ii. Fluticasone Propionate 0.05% (w/w) cannot, by themselves, be deposited directly onto human skin 0.055 iii. Mometasone Furoate 0.1% (w/w) due to their harshness. 0056 iv. Dexamethasone Acetate—0.1% (w/w) 0044) The cream base of the present invention optionally 0057 v. Hydrocortisone Acetate 1.0% (w/w) further comprises an ingredient selected from a group com 0.058 vi. Clobetasol Propionate 0.05% (w/w) prising a preservative, a buffering agent, an anti oxidant, a 0059 vii. Beclomethasone Dipropionate 0.025% chelating agent, and a humectant, or any combination thereof. (w/w) 0045. The present invention provides a novel cream that 0060 viii. Betamethasone Dipropionate 0.05% has been produced using Sodium Fusidate as the starting raw (w/w) material, and which cream contains Fusidic acid of high wherein all percentages are with respect to the final formula therapeutic efficacy and of chemical stability that is generally tion. Superior to the commercially available creams containing 0061 The product used for the Stability Studies tests con Fusidic acid. tained approximately 10% extra APIs (overages). It was pack US 2011/028 1830 A1 Nov. 17, 2011 aged in an aluminium collapsible tube and each gram of the product contained 20.8 mg of Sodium Fusidate (in conform TABLE 4 ance with BP), which is equivalent to 20 mg of Fusidic acid pH Test, Batch No. SBV-01 (BP conformant). Measured parameter: pH; Limits of measured parameter: 3-6 i) PRODUCT: Sodium Fusidate+Betamethasone Valerate Method of measurement: Digital pH Meter Cream Conditions Initial 1 Month 2” Month 3 Month PACK: Aluminum Collapsible Tube 40° C. 75% RH 4.25 4.24 4.23 4.24 30° C. 65% RH 4.23 4.24 4.23 0062 25° C. 60% RH 4.24 4.23 4.24 Temperature cycling 4.23 Freezthaw 4.22

Composition: Each gm contains: i) Sodium Fusidate BP Equivalent to Fusidic Acid BP 2.0% TABLE 5 ii) Betamethasone Valerate IP O.12% Assay (%) Test, Batch No. SBV-01 Measured parameter: Assay (%); Limits of measured parameter: 90-110 Method of measurement: HPLC Method TABLE 3 1st 2nd 3rd Description Test, Batch No. SBV-01 Conditions Assay (%) Initial Month Month Month00 Measured parameter: Physical appearance 40° C. 75% i) Fusidic acid 108.57 108.46 108.16 108.11 Best value of measured parameter: Homogeneous White to off RH ii) Betamethasone 109.56 109.51 109.32 109.11 White Viscous cream Valerate Method of measurement. Observation by naked eye 30° C. 65% i) Fusidic acid 108.53 108.41 108.36 RH ii) Betamethasone 109.48 10942 109.20 Conditions Initial 1 Month 2” Month 3 Month Valerate 40° C. Homogenous Homogenous Homogenous Homogenous 25° C. 60% i) Fusidic acid 108.54 108.42 108.40 75% RH White to off White to off White to off White to off RH ii) Betamethasone 109.54 10942 10921 White viscous White White White Valerate C8 viscous viscous viscous Temperature i) Fusidic acid 107.53 Ce3 Ce3 C8 cycling ii) Betamethasone 109.51 30° C. Homogenous Homogenous Homogenous Valerate 65% RH White to off White to off White to off Freezthaw i) Fusidic acid 108.01 White White White ii) Betamethasone 108.25 viscous viscous viscous Valerate Ce3 Ce3 C8 25o C. Homogenous Homogenous Homogenous 60% RH White to off White to off White to off ii) PRODUCT: sodium Fusidate+Fluticasone Propionate White White White Cream viscous viscous viscous Ce3 Ce3 C8 Temperature — Homogenous — PACK: Aluminum Collapsible Tube cycling White to off White 0063 viscous Ce3 Freezthaw Homogenous — White to off Composition: Each gm contains: White viscous i) Sodium Fusidate BP Equivalent to Fusidic Acid BP 2.0% Ce3 ii) FluticasOne Propionate BP O.05%

TABLE 6 Description Test, Batch No. SFC-01 Measured parameter: Physical appearance Best value of measured parameter: Homogeneous White to off White Viscous Method of measurement: Observation by naked eye 1st 2nd 3rd 6 i Conditions Initial Month Month Month Month 40° C. 75% RH Homogenous Homogenous Homogenous Homogenous Homogenous White to off White to White to White to White to White Off Off Off Off viscous White White White White Ce:8 viscous viscous viscous viscous US 2011/028 1830 A1 Nov. 17, 2011

TABLE 6-continued Description Test, Batch No. SFC-01 Measured parameter: Physical appearance Best value of measured parameter: Homogeneous White to off White Viscous Method of measurement. Observation by naked eye 1st 2nd 3rd 6th Conditions Initial Month Month Month Month 30° C. 65% RH Homogenous Homogenous Homogenous Homogenous White to White to White to White to O Off Off Off White White White White viscous viscous viscous viscous Ce:8 Ce3 C8 Ce:8 25° C. 60% RH Homogenous Homogenous Homogenous Homogenous White to White to White to White to O Off Off Off White White White White viscous viscous viscous viscous Ce:8 Ce3 C8 Ce:8 Temperature Homogenous — cycling White to O White viscous Ce:8 Freezthaw Homogenous — White to O White viscous Ce:8

TABLE 7 TABLE 7-continued

pH Test, Batch No. SFC-01 pH Test, Batch No. SFC-01 Measured parameter: pH; Limits of measured parameter: 3-6: Method of Measured parameter: pH; Limits of measured parameter: 3-6: Method of measurement: Digital pH Meter measurement: Digital pH Meter Conditions Initial 1 Month 2 Month 3Month 6 Month Conditions Initial 1 Month 2 Month 3Month 6 Month Temperature 3.49 40° C. 75% RH 3.51 3.SO 3.48 3.49 3.48 cycling 30° C. 65% RH 3.SO 3.49 3.48 3.47 Freezthaw 3.48 25° C. 60% RH 3.51 3.49 3.SO 3.49

TABLE 8 Assay (%) Test, Batch No. SFC-01 Measured parameter: Assay (%) Limits of measured parameter: 90-110 Method of measurement: HPLC Method 1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month

40° C. 75% i) Fusidic acid 108.68 108.56 108.36 108.21 108.18 RH ii) Fluticasone 108.56 108.51 108.32 108.11 108.08 Propionate 30° C. 65% i) Fusidic acid 108.53 108.31 108.26 108.22 RH ii) Fluticasone 108.48 108.42 108.2O 108.11 Propionate 25° C. 60% i) Fusidic acid 108.64 108.52 108.48 108.38 RH ii) Fluticasone 108.54 108.42 108.21 108.10 Propionate Temperature i) Fusidic acid 108.10 cycling ii) Fluticasone 108.51 Propionate US 2011/028 1830 A1 Nov. 17, 2011

TABLE 8-continued Assay (%) Test, Batch No. SFC-01 Measured parameter: Assay (%) Limits of measured parameter: 90-110 Method of measurement: HPLC Method 1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month Freezthaw i) Fusidic acid 108.21 ii) Fluticasone 108.15 Propionate iii) PRODUCT: Sodium Fusidate+Mometasone Furoat Ca TABLE 9-continued Description Test, Batch No. SFM-01 PACK: Aluminum Collapsible Tube 1st 2nd 3rd 6th Conditions Initial Month Month Month Month 0.064 25o C. Do Do Do Do 60% RH Temperature Do cycling Composition: Each gm contains: Freezthaw Do i) Sodium Fusidate BP Equivalent 2.0% Measured parameter: Physical appearance to Fusicic Acid BP Best value of measured parameter: Homogeneous White to off White Viscous cream; ii) Mometasone Furoate USP O.1% Method of measurement; Observation by naked eye

TABLE 10 TABLE 9 pH Test, Batch No. SFM-01 Description Test, Batch No. SFM-01 1st 2nd 3rd 6th 1st 2nd 3rd 6th Conditions Initial Month Month Month Month Conditions Initial Month Month Month Month 40° C. 75% RH 3.54 3.53 3.52 3.53 3.52 40° C. Homo- Homo- Homo- Homo- Homo 30° C. 65% RH 3.52 3.53 3.54 3.53 75% RH genous genous genous genous genous 25° C. 60% RH 3.53 3.54 3.53 3.52 White White White White White Temperature 3.52 to off to off to off to off to off cycling White White White White White Freezthaw 3.53 viscous viscous viscous viscous viscous Ce3 Ce3 Ce3 Ce3 Ce:8 Measured parameter: pH: 30° C. Do Do Do Do Limits of measured parameter: 3-6 65% RH Method of measurement: Digital pH Meter

TABLE 11 Assay (%) Test, Batch No. SFM-01 Measured parameter: Assay (%) Limits of measured parameter: 90-110; Method of measurement: HPLC Method 1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month

40° C. 75% i) Fusidic acid 108.27 108.26 108.14 108.08 107.89 RH ii) Mometasone 108.56 108.51 108.32 108.11 107.88 Furoate 30° C. 65% i) Fusidic acid 108.23 108.21 108.16 107.92 RH ii) Mometasone 108.48 108.42 108.2O 107.75 Furoate 25° C. 60% i) Fusidic acid 108.24 108.22 108.2O 107.95 RH ii) Mometasone 108.54 108.42 108.21 107.82 Furoate Temperature i) Fusidic acid 107.63 cycling ii) Mometasone 108.51 Furoate US 2011/028 1830 A1 Nov. 17, 2011

TABLE 1 1-continued Assay (%) Test, Batch No. SFM-01 Measured parameter: Assay (%) Limits of measured parameter: 90-110; Method of measurement: HPLC Method 1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month Freezthaw i) Fusidic acid 108.11 ii) Mometasone 108.15 Furoate iv) PRODUCT: Sodium Fusidate--Dexamethasone Acetate Cream TABLE 1.4 PACK: Aluminum Collapsible Tube Assay (%) Test, Batch No. SFD-01 1st 2nd 3rd 0065 Conditions Assay (%) Initial Month Month Month 40° C. i) Fusidic acid 108.62 108.58 108.44 108.30 75% RH ii) Dexamethasone 108.15 108.14 108.12 108.05 Acetate 30° C. i) Fusidic acid 108.63 108.52 108.32 Composition: Each gm contains: 65% RH ii) Dexamethasone 108.14 108.12 108.09 Acetate 25o C. i) Fusidic acid 108.60 108.54 108.46 i) Sodium Fusidate BP Equivalent 2.0% 60% RH ii) Dexamethasone 108.14 108.11 108.10 Acetate to Fusicic Acid BP Temperature i) Fusidic acid 108.52 ii) Dexamethasone Acetate IP O.1% cycling ii) Dexamethasone 107.68 Acetate Freezthaw i) Fusidic acid 108.41 ii) Dexamethasone 107.84 Acetate TABLE 12 Measured parameter: Assay (%); Description Test, Batch No. SFD-01 Limits of measured parameter: 90-110 1st 2nd 3rd Method of measurement: HPLC Method Conditions Initial Month Month Month

40° C. 75% RH Homo- Homo- Homo- Homo genous genous genous genous v) PRODUCT: Sodium Fusidate+Hydrocortisone Acetate White White White White Cream to off to off to off to off White White White White PACK: Aluminum Collapsible Tube viscous viscous viscous viscous C8 C8 Ce:8 Ce3 0066 30° C. 65% RH Do Do Do 25° C. 60% RH Do Do Do Temperature Do cycling Freezthaw Do Composition: Each gm contains: Measured parameter: Physical appearance i) Sodium Fusidate BP Equivalent to 2.0% Best value of measured parameter: Homogeneous White to off White Viscous cream Fusicic Acid BP Method of measurement; Observation by naked eye ii) Hydrocortisone Acetate IP 1.0%

TABLE 13 TABLE 1.5 pH Test, Batch No. SFD-01 Conditions Initial 1st Month 2nd Month 3rd Month Description Test, Batch No. HAS-Ol

40° C. 75% RH 4.22 4.21 4.20 4.2O Conditions Initial 1st Month 2nd Month 3rd Month 30° C. 65% RH 4.22 4.21 4.2O 25° C. 60% RH 4.21 4.21 4.2O 40° C. Homo- Homo- Homo- Homo Temperature 4.21 75% RH genous genous genous genous cycling White White White White Freezthaw 4.2O to off to off to off to off White White White White Measured parameter: pH viscous viscous viscous viscous Limits of measured parameter: 3-6 Ce3 Ce3 Ce3 C8 Method of measurement: Digital pH Meter 30° C. 65% RH Do Do Do 25° C. 60% RH Do Do Do US 2011/028 1830 A1 Nov. 17, 2011

Vi) PRODUCT: Sodium Fusidate+Clobetasol Propionate TABLE 15-continued Cream Description Test, Batch No. HAS-Ol PACK: Aluminum Collapsible Tube Conditions Initial 1st Month 2nd Month 3rd Month 0067 Temp cycling Do Freezthaw Do Measured parameter: Physical appearance Best value of measured parameter: Homogeneous White to off White Viscous cream; Composition: Each gm contains: Method of measurement; Observation by naked eye i) Sodium Fusidate BP Equivalent 2.0% to Fusicic Acid BP TABLE 16 ii) Clobetasol Propionate USP O.05% pH Test, Batch No. HAS-01 1st 2nd 3rd Conditions Initial Month Month Month TABLE 1.8 40° C. 75% RH 4.31 4.30 4.29 4.28 30° C. 65% RH 4.31 4.30 4.29 Description Test, Batch No. SPC-01 25° C. 60% RH 4.30 4.29 4.28 1st 2nd 3rd 6th Temperature 4.29 Conditions Initial Month Month Month Month cycling Freezthaw 4.28 40° C. 75% RH Homo- Homo- Homo- Homo- Homo genous genous genous genous genous Measured parameter: pH White White White White White Limits of measured parameter: 3-6 to off to off to off to off to off Method of measurement: Digital pH Meter White White White White White viscous viscous viscous viscous viscous Ce3 Ce:8 Ce3 Ce3 Ce8 TABLE 17 30° C. 65% RH Do Do Do Do 25° C. 60% RH Do Do Do Do Assay (%) Test, Batch No. HAS-01 Temp cycling DO 1st 2nd 3rd Freezthaw Do Conditions Assay (%) Initial Month Month Month Measured parameter: Physical appearance 40° C. i) Fusidic acid 108.52 O848. 108.34 108.20 Best value of measured parameter: Homogeneous White to off White Viscous cream 75% RH ii) Hydrocortisone 107.15 O7.14 107.12 107.05 Method of measurement; Observation by naked eye Acetate 30° C. i) Fusidic acid O851 108.42 108.32 65% RH ii) Hydrocortisone O7.14 107.12 107.09 TABLE 19 Acetate 25o C. i) Fusidic acid O8.50 108.44 108.36 pH Test, Batch No. SPC-01 60% RH ii) Hydrocortisone O7.14 107.11 107.10 1st 2nd 3rd 6th Acetate Conditions Initial Month Month Month Month Temperature i) Fusidic acid O840 cycling ii) Hydrocortisone O7.11 40° C. 75% RH 4.22 4.21 4.20 4.2O 4.19 Acetate 30° C. 65% RH 4.21 4.20 4.19 4.18 Freezthaw i) Fusidic acid O8.31 25° C. 60% RH 4.22 4.21 4.2O 4.20 ii) Hydrocortisone O7.14 Temp cycling 4.2O Acetate Freezthaw 4.19 Measured parameter: Assay (%) Measured parameter: pH Limits of measured parameter: 90-110 Limits of measured parameter: 3-6 Method of measurement: HPLC Method Method of measurement: Digital pH Meter

TABLE 20 Assay (%) Test, Batch No. SPC-01 Measured parameter: Assay (%); Limits of measured parameter: 90-110 Method of measurement: HPLC Method

1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month

40° C. 75% i) Fusidic acid 108.38 108.33 108.24 108.10 108.01 RH ii) Clobetasol 107.41 107.34 107.22 107.15 107.10 Propionate 30° C. 65% i) Fusidic acid 108.31 108.32 108.22 108.11 RH ii) Clobetasol 107.38 107.32 107.29 107.22 Propionate US 2011/028 1830 A1 Nov. 17, 2011

TABLE 20-continued Assay (%) Test, Batch No. SPC-01 Measured parameter: Assay (%); Limits of measured parameter: 90-110 Method of measurement: HPLC Method

1st 2nd 3rd 6th Conditions Assay (%) Initial Month Month Month Month 25° C. 60% i) Fusidic acid 108.30 108.24 108.15 108.08 RH ii) Clobetasol 10740 107.34 107.30 107.24 Propionate Temperature i) Fusidic acid 108.28 cycling ii) Clobetasol 107.21 Propionate Freezthaw i) Fusidic acid 108.22 ii) Clobetasol 107.11 Propionate vii) PRODUCT: Sodium Fusidate+Beclomethasone Dipropi onate Cream TABLE 22

PACK: Aluminum Collapsible Tube pH Test, Batch No. SFB-01 Measured parameter: pH 0068 Limits of measured parameter: 3-6 Method of measurement: Digital pH Meter

Composition: Each gm contains: Conditions Initial 1st Month 2nd Month 3rd Month

i) Sodium Fusidate BP 2.0% 40° C. 75% RH 4.33 4.32 4.32 4.31 (Equivalent to Fusidic Acid BP) 30° C. 65% RH 4.31 4.30 4.31 ii) Beclomethasone dipropionate IP O.025% 25° C. 60% RH 4.32 4.33 4.32 Temperature 4.31 cycling TABLE 21 Freezthaw 4.32

Description Test, Batch No. SFB-01 Measured parameter: Physical appearance Best value of measured parameter: Homogeneous White to off White TABLE 23 Viscous cream: Method of measurement. Observation by naked eye Assay (%) Test, Batch No. SFB-01 Conditions Initial 1st Month 2nd Month 3rd Month Measured parameter: Assay (%); Limits of measured parameter: 90-110 Method of measurement: HPLC Method 40° C. Homogenous Homogenous Homogenous Homogenous 75% RH White to White to White to White to 1st 2nd 3rd of White off White off White of White Conditions Assay (%) Initial Month Month Month WISCOS WISCOS WISCOS WISCOS C8 Ce3 Ce3 C8 40° C. 75% i) Fusidic aci 108.28 O8.25 108.20 108.12 30° C. Homogenous Homogenous Homogenous RH ii) 108.12 O8.04 107.98 107.88 65% RH White to White to White to Becomethasone off White off White off White ipropionate WISCOS WISCOS WISCOS 30° C. 65% i) Fusidic aci O8.25 108.22 108.18 Ce3 Ce3 C8 RH ii) O8.11 107.96 107.68 25o C. Homogenous Homogenous Homogenous Becomethasone 60% RH White to White to White to ipropionate off White of White off White 25° C. 60% i) Fusidic aci O8.22 108.18 108.15 WISCOS WISCOS WISCOS RH ii) O8.OS 108.OO 107.90 Ce3 Ce3 C8 Becomethasone Temp cycling — Homogenous — ipropionate White to Temperature i) Fusidic aci O8.23 o White cycling ii) O7.68 WISCOS Becomethasone Ce3 ipropionate Freezthaw Homogenous — Freezthaw i) Fusicic aci O8.11 White to ii) O7.58 o White Becomethasone WISCOS ipropionate US 2011/028 1830 A1 Nov. 17, 2011

viii) PRODUCT: Sodium Fusidate--Betamethasone Dipropi onate Cream TABLE 26 Assay (%) Test, Batch No. STD-01 PACK: Aluminum Collapsible Tube Measured parameter: Assay (%) Limits of measured parameter: 90-110 0069 Method of measurement: HPLC Method 1st 2nd 3rd Conditions Assay (%) Initial Month Month Month 40° C. 75% i) Fusidic acid 108.82 108.78 108.70 108.52 Composition: Each gm contains: RH ii) Betamethasone 107.52 107.44 107.38 107.28 dipropionate 30° C. 65% i) Fusidic acid 108.75 108.62 108.48 i) Sodium Fusidate BP Equivalent to Fusidic Acid BP 2.0% RH ii) Betamethasone 107.48 107.36 107.22 ii) Betamethasone dipropionate USP 0.05% dipropionate 25° C. 60% i) Fusidic acid 108.62 108.58 108.45 RH ii) Betamethasone 107.28 107.21 107.19 dipropionate Temperature i) Fusidic acid 108.63 TABLE 24 cycling ii) Betamethasone 107.28 dipropionate Description Test, Batch No. STD-01 Freezthaw i) Fusidic acid 108.41 Measured parameter: Physical appearance ii) Betamethasone 107.38 Best value of measured parameter: Homogeneous White to dipropionate off White Viscous cream Method of measurement. Observation by naked eye 0070 From the above data, it is evident that product of the Conditions Initial 1st Month 2nd Month 3rd Month present invention is quite stable at ambient conditions and also at elevated temperature & humid conditions of storage. 40° C. Homogenous Homogenous Homogenous Homogenous 0071. According to the preferred embodiment of the 75% RH White to White to White to White to off White off White off White off White present invention, there is provided a single dose composition viscous viscous viscous viscous comprising at least one steroid and at least one antibacterial C8 Ce3 Ce:8 Ce:8 agent for the topical treatment of bacterial skin infections and 30° C. Homogenous Homogenous Homogenous inflammations on human skin, the composition comprising a 65% RH White to White to White to steroid selected from a group comprising Betamethasone Val off White off White off White viscous viscous viscous erate, Fluticasone Propionate, Mometasone Furoate, Dexam Ce3 Ce:8 Ce:8 ethasone Acetate, Hydrocortisone Acetate, Clobetasol Propi 25o C. Homogenous Homogenous Homogenous onate, Beclomethasone Dipropionate, Betamethasone 60% RH White to White to White to Dipropionate and the like, and Fusidic acid made in situ by a off White off White off White conversion of Sodium Fusidate, a cream base containing pri viscous viscous viscous mary and secondary emulsifiers, waxy materials, co-solvents, Ce3 Ce:8 Ce:8 and acids, and water. Temperature — Homogenous — 0072 The proportions of various components of the pre cycling White to ferred embodiment are as follows: off White viscous 0.073 a. Fusidic acid from about 0.1% (w/w) to about Ce3 25% (w/w) by weight, preferably from about 0.5% Freezthaw Homogenous — (w/w) to about 5% (w/w) by weight and more preferably White to about 2.00% (w/w), which has been converted in situ off White from Sodium Fusidate from about 0.1% (w/w) to about viscous 25% (w/w) by weight, preferably from about 0.5% Ce3 (w/w) to about 5% (w/w) by weight and more preferably about 2.08% (w/w), and from about 0.001% (w/w) to about 5% (w/w) by weight, preferably from about 0.005% (w/w) to about 2.00% (w/w) by weight, and TABLE 25 most preferably from about 0.05% (w/w) to 1.0% (w/w) pH Test, Batch No. STD-01 by weight, of a active compound, Measured parameter: pH 0074 b. a cream base containing primary and secondary Limits of measured parameter: 3-6 emulsifiers, waxy materials, co-solvents, acids, and Method of measurement. Digital pH Meter water wherein Conditions Initial 1st Month 2nd Month 3rd Month 0075 primary and secondary emulsifiers are selected from a group comprising Cetostearyl alcohol, 40° C. 75% RH 4.31 4.30 4.31 4.30 30° C. 65% RH 4.31 4.30 4.31 Cetomacrogol-1000, Polysorbate-80, Span-80 and 25° C. 60% RH 4.30 4.31 4.31 the like from about 1% (w/w) to 15% (w/w), prefer Temperature 4.31 ably 15% (w/w), more preferably 14.5% (w/w) cycling 0076 waxy materials are selected from a group com Freezthaw 4.30 prising White Soft Paraffin, Liquid Paraffin, Hard Par affin and the like from about 5% (w/w) to 20% (w/w), preferably 15% (w/w), more preferably 12.5% (w/w), US 2011/028 1830 A1 Nov. 17, 2011

0077 co-solvents are selected from a group compris Composition of the Typical Cream of the Preferred Embodi ing Propylene Glycol, Hexylene Glycol, PolyEthyl ment of the Present Invention and on which the Experimental ene Glycol-400 and the like from about 5% (w/w) to Results Presented in the Foregoing Description have been 40% (w/w), preferably 30% (w/w), more preferably Based are Now Provided. 25% (w/w), 0078 acids are selected from a group comprising TABLE 27 HCl, H2So4, HNO3, Lactic acid and the like from about 0.005% (w/w) to 0.5% (w/w), preferably 0.3% i. Sodium Fusiciate + Betamethasone Valerate Cream (w/w), more preferably 0.25% (w/w), and (0079 water in the amount in the range of 20% (w/w) S. to 75% (w/w), preferably 35% (w/w) to 50% (w/w), No Ingredients Specification % (w.fw) more preferably 40% (w/w) to 43% (w/w), preferably 1 Fusicic acid made from Sodium Fusiciate BP 2.OO purified water. 2 Betamethasone Valerate P O.12 0080. In another embodiment of the present invention the 3 Cetostearyl Alcohol P 12.5 product of the preferred embodiment is further provided with 4. White Soft Paraffin P 12.5 preservatives, wherein said preservatives are selected from a 5 Polysorbate 80 P 2 group comprising Methylparaben, Propylparaben, Chloro 6 Propylene Glycol P 25 cresol, Potassium sorbate, Benzoic acid and the like from 7 Benzoic Acid P O.2 about 0.05% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), 8 Butylated Hydroxy Toluene P O.O1 more preferably 0.2% (w/w). 9 Disodium Edetate P O.1 0081. In a still further embodiment of the present inven 10 1M Nitric Acid P 4.0 tion, the product of the preferred embodiment is further pro 11 Disodium hydrogen Orthophosphate P O.OS vided with a buffering agent selected from a group compris anhydrous ing Di Sodium Hydrogen Ortho Phosphate, Sodium 12 Purified Water P 41.56 Hydrogen Ortho Phosphate and the like from about 0.01% (w/w) to 1.00% (w/w), preferably 0.5% (w/w), more prefer ably 0.05% (w/w). TABLE 28 0082 In yet another embodiment of the present invention, the product of the preferred embodiment is further provided ii. Sodium Fusidate + FluticasOne Propionate Crean with an anti oxidants are selected from a group comprising S. Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and No Ingredients Specification % (w.fw) the like from about 0.001% (w/w) to 5% (w/w), preferably 1 Fusicic acid made from Sodium Fusiciate BP 2.OO 0.1% (w/w), more preferably 0.01% (w/w). 2 FluticasOne Propionate BP O.OS 3 Cetostearyl Alcohol IP 12.5 0083) Inafurther embodiment of the present invention, the 4. White Soft Paraffin IP 12.5 product of the preferred embodiment is further provided with 5 Polysorbate 80 IP 2 a chelating selected from a group comprising Disodium 6 Propylene Glycol IP 25 7 Benzoic Acid IP O.2 EDTA and the like from about 0.01% (w/w) to 1% (w/w), 8 Butylated Hydroxy Toluene IP O.O1 preferably 0.5% (w/w), more preferably 0.1% (w/w). 9 Disodium Edetate IP O.1 10 1M Nitric Acid IP 4.0 0084. In still another embodiment of the present invention, 11 Disodium hydrogen Orthophosphate IP O.OS the product of the preferred embodiment is further provided anhydrous with a humectant selected from a group comprising Glycerin, 12 Purified Water IP 41.6 Sorbitol, Propylene glycol and the like from about 5% (w/w) to 40% (w/w) preferably 30% (w/w), more preferably 25% (w/w). 0085. In another embodiment of the present invention, the TABLE 29 product of the preferred embodiment further is provided with iii. Sodium Fusiciate + Mometasome Furoate Cream at least one component selected from a group comprising buffering agents, preservatives, anti oxidants, chelating S. % agents, humectants, or any combination thereof in respective No Ingredients Specification (ww) proportions disclosed in the earlier described embodiments. 1 Fusicic acid made from Sodium Fusiciate BP 2.OO 2 Mometasome Furoate USP O.1 I0086. In a further embodiment of the present invention, a 3 Cetostearyl Alcohol P 12.5 novel dermaceutical cream is disclosed wherein sodium fusi 4. White Soft Paraffin P 12.5 date is converted in-situ under totally oxygen free environ 5 Polysorbate 80 P 2 6 Propylene Glycol P 25 ment by slow addition of an acid, into Fusidic acid of a 7 Benzoic Acid P O.2 molecular dispersion form (due to the presence of a co-sol 8 Butylated Hydroxy Toluene P O.O1 Vent) at the intermediate stage, and which Fusidic acid regen 9 Disodium Edetate P O.1 erates into an extremely finely dispersed form when added to 10 1M Nitric Acid P 4.0 a final cream base, thereby resulting in a finely and homoge 11 Disodium hydrogen Orthophosphate anhydrous IP O.OS neously dispersed Fusidic acid in the final cream; all opera 12 Purified Water P 41.56 tions of converting sodium fusidate into Fusidic acid carried out preferably in an environment free of atmospheric oxygen. US 2011/028 1830 A1 Nov. 17, 2011 12

TABLE 30 TABLE 33-continued iv. Sodium Fusiciate + Dexamethasone Acetate Cream vii. Sodium Fusidate + Becomethasone Dipropionate Cream S. % No Ingredients Specification (wfw) S. No Ingredients Specification (wiw) Fusicic acid made from Sodium Fusiciate BP 2.OO 5 Polysorbate 80 IP 2 Dexamethasone Acetate BP O.1 6 Propylene Glycol IP 25 Cetostearyl Alcohol IP 12.5 7 Benzoic Acid IP O.2 White Soft Paraffin IP 12.5 8 Butylated Hydroxy Toluene IP O.O1 Polysorbate 80 IP 9 Disodium Edetate IP O.1 Propylene Glycol IP 25 10 1M Nitric Acid IP 4.0 Benzoic Acid IP O.2 11 Disodium hydrogen Orthophosphate IP O.OS Butylated Hydroxy Toluene IP O.O1 anhydrous Disodium Edetate IP O.1 12 Purified Water IP 41.6 1M Nitric Acid IP 4.0 Disodium hydrogen Orthophosphate anhydrous IP O.OS Purified Water IP 41.56 TABLE 34 viii. Sodium Fusidate + Betamethasone Dipropionate Crean TABLE 31 S. % V. Sodium Fusidate + Hydrocortisone Acetate Crean No Ingredients Specification (ww)

S. % 1 Fusicic acid made from Sodium Fusiciate BP 2.OO No Ingredients Specification 2 Betamethasone Dipropionate USP O.OS (wfw) 3 Cetostearyl Alcohol IP 12.5 Fusicic acid made from Sodium Fusiciate BP 2.OO 4. White Soft Paraffin IP 12.5 Hydrocortisone Acetate IP 1 5 Polysorbate 80 IP 2 Cetostearyl Alcohol IP 12.5 6 Propylene Glycol IP 25 White Soft Paraffin IP 12.5 7 Benzoic Acid IP O.2 Polysorbate 80 IP 2 8 Butylated Hydroxy Toluene IP O.O1 Propylene Glycol IP 25 9 Disodium Edetate IP 0.1 Benzoic Acid IP O.2 10 1M Nitric Acid IP 4.0 Butylated Hydroxy Toluene IP O.O1 11 Disodium hydrogen Orthophosphate anhydrous IP O.OS Disodium Edetate IP O.1 12 Purified Water IP 41.6 1M Nitric Acid IP 4.0 Disodium hydrogen Orthophosphate anhydrous IP O.OS Purified Water IP 40.65 I0087. It is evident from the foregoing description that the present invention comprises the following embodiments. 0088 1. A novel dermaceutical cream containing at least one corticosteroid, and Fusidic acid which is made TABLE 32 in situ under oxygen-free environment using Sodium vi. Sodium Fusidate + Clobetasol Propionate Crean Fusidate, wherein said cream comprises Fusidic acid made in situ by a conversion of Sodium Fusidate, and a S. % cream base containing at least one of each of a preser No Ingredients Specification (wfw) Vative, a primary and secondary emulsifier, a waxy Fusicic acid made from Sodium Fusiciate BP 2.OO material, a co-solvents, an acid, and water, preferably Clobetasol Propionate USP O.OS purified water. Cetostearyl Alcohol IP 12.5 White Soft Paraffin IP 12.5 0089 2. A novel dermaceutical cream as described in Polysorbate 80 IP 2 item 1, wherein said corticosteroid is added from about Propylene Glycol IP 25 0.001% (w/w) to about 5% (w/w) by weight, preferably Benzoic Acid IP O.2 Butylated Hydroxy Toluene IP O.O1 from about 0.005% (w/w) to about 2.00% (w/w) by Disodium Edetate IP O.1 weight, and most preferably from about 0.05% (w/w) to 1M Nitric Acid IP 4.0 1.0% (w/w) by weight and said Fusidic acid is present in Disodium hydrogen Orthophosphate anhydrous IP O.OS an amount from about 0.1% (w/w) to about 25% (w/w), Purified Water IP 41.6 preferably from about 0.5% (w/w) to about 5% (w/w), and more preferably about 2.00% (w/w), and in which the amount of said Sodium Fusidate used to form in situ TABLE 33 said Fusidic acid is in the range between about 0.1% (w/w) to about 25% (w/w), preferably from about 0.5% vii. Sodium Fusidate + Becomethasone Dipropionate Cream (w/w) to about 5% (w/w) and more preferably about % 2.08% (w/w), and S. No Ingredients Specification (wfw) 0090 said preservatives is selected from a group com prising Methylparaben, Propylparaben, Chlorocresol, Fusidic acid made from Sodium Fusiciate BP 2.OO Beclomethasone Dipropionate IP O.O2S Potassium sorbate, Benzoic acid and the like, either Cetostearyl Alcohol IP 12.5 singly or any combination thereof, to form a proportion White Soft Paraffin IP 12.5 from about 0.05% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.2% (w/w), US 2011/028 1830 A1 Nov. 17, 2011 13

0091 said primary and secondary emulsifier is selected an extremely finely dispersed form when added to a final from a group comprising Cetostearyl alcohol, Cetomac cream base, thereby resulting in a finely and homoge rogol-1000, Polysorbate-80, Span-80 and the like, either neously dispersed Fusidic acid in the final cream; all singly or any combination thereof, to form a proportion operations of converting sodium fusidate into Fusidic from about 1% (w/w) to 15% (w/w), preferably 15% acid carried out preferably in an environment free of (w/w), more preferably 14.5% (w/w), atmospheric oxygen. 0092 said waxy material is selected from a group com 01.01 8. A novel dermaceutical cream as described in prising White soft paraffin, Liquid Paraffin, Hard paraf items 1 to 7 wherein said conversion of Sodium Fusidate finand the like, either singly or any combination thereof, into said Fusidic acid and the following formation of to form a proportion from about 5% (w/w) to 20% said Fusidic acid in a finely dispersed form in the final (w/w), preferably 15% (w/w), more preferably 12.5% cream base take place in an oxygen-free environment. (w/w), 01.02 9. A novel dermaceutical cream as described in 0093 said co-solvent is selected from a group compris item 8 wherein said oxygen-free environment comprises ing Propylene Glycol, Hexylene Glycol, PolyEthylene a gaseous environment formed of inert gas selected from Glycol-400 and the like, either singly or any combina a group comprising carbon dioxide, nitrogen, helium tion thereof, to form a proportion from about 5% (w/w) and the like. to 40% (w/w), preferably 30% (w/w), more preferably (0103) 10. A method of treating primary & secondary 25% (w/w), skin infections and inflammations said method compris 0094) said acid is selected from a group comprising ing applying of a cream containing at least one corticos acids such as HCl, H2So4, HNO3, Lactic acid and the teroid and Fusidic acid which is made in situ under like, either singly or any combination thereof, to form a oxygen-free environment using Sodium Fusidate, proportion from about 0.005% (w/w) to 0.5% (w/w), wherein said cream comprises Fusidic acid made using preferably 0.3% (w/w), more preferably 0.25% (w/w), Sodium Fusidate, a cream base containing a preserva and tive, primary and secondary emulsifiers, waxy materials, 0.095 water in the amount in the range of 20% (w/w) to co-solvents, acids, and water. 75% (w/w), preferably 35% (w/w) to 50% (w/w), more 01.04 11. A method of treating primary & secondary preferably 40% (w/w) to 43% (w/w), preferably purified skin infections and inflammations said method compris Water. ing applying of a cream as described in item 10, wherein 0096 3. A novel dermaceutical cream as described in said cream further comprises any of a group comprising item 1 which further comprises a buffering agent, a buffering agent, an antioxidant, a chelating agent, and wherein said buffering agent is selected from a group a humectant, or any combination thereof. comprising Di Sodium Hydrogen Ortho Phosphate, 01.05 12. A method of treating primary & secondary Sodium Hydrogen Ortho Phosphate and the like, either skin infections and inflammations said method compris singly or any combination thereof, to form a proportion ing applying of a cream as described in item 11, wherein from about 0.01% (w/w) to 1.00% (w/w), preferably said corticosteroid is added from about 0.001% (w/w) to 0.5% (w/w), more preferably 0.05% (w/w). about 5% (w/w) by weight, preferably from about 0097. 4. A novel dermaceutical cream as described in 0.005% (w/w) to about 2.00% (w/w) by weight, and items 1 to 3 which further comprises an anti-oxidant, most preferably from about 0.05% (w/w) to 1.0% (w/w) wherein said anti-oxidant is selected from a group com by weight, prising Butylated Hydroxy Anisole. Butylated Hydroxy 01.06 said Fusidic acid is present in an amount from Toluene and the like, either singly or any combination about 0.1% (w/w) to about 25% (w/w), preferably from thereof, to form a proportion from about 0.001% (w/w) about 0.5% (w/w) to about 5% (w/w), and more prefer to 5% (w/w), preferably 0.1% (w/w), more preferably ably about 2.00% (w/w), and in which the amount of 0.01% (w/w). Sodium Fusidate used to form in situ said Fusidic acid is 0.098 5. A novel dermaceutical cream as described in in the range between about 0.1% (w/w) to about 25% items 1 to 4 which further comprises a chelating agent, (w/w), preferably from about 0.5% (w/w) to about 5% wherein said chelating agent is selected from a group (w/w) and most preferably about 2.08% (w/w), comprising Disodium EDTA and the like, either singly 01.07 said primary and secondary emulsifier is selected or any combination thereof, to form a proportion from from a group comprising Cetostearyl alcohol, Cetomac about 0.01% (w/w) to 1% (w/w), preferably 0.5% (w/w), rogol-1000, Polysorbate-80, Span-80 and the like, either more preferably 0.1% (w/w). singly or any combination thereof, to form a proportion 0099. 6. A novel dermaceutical cream as described in from about 1% (w/w) to 15% (w/w), preferably 15% items 1 to 5 which further comprises a humectant, (w/w), more preferably 14.5% (w/w), wherein said humectant is selected from a group com 01.08 said waxy material is selected from a group com prising Glycerin, Sorbitol, Propylene glycoland the like, prising white soft paraffin, liquid paraffin, Hard paraffin either singly or any combination thereof, to form a pro and the like, either singly or any combination thereof, to portion from about 5% (w/w) to 40% (w/w), preferably form a proportion from about 5% (w/w) to 20% (w/w), 30% (w/w), more preferably 25% (w/w). preferably 15% (w/w), more preferably 12.5% (w/w), 0.100 7. A novel dermaceutical cream as described in 0109) said co-solvent is selected from a group compris items t to 6 wherein sodium fusidate is converted in-situ ing Propylene Glycol, Hexylene Glycol, PolyEthylene under totally oxygen free environment by slow addition Glycol-400 and the like, either singly or any combina of an acid, into Fusidic acid of a molecular dispersion tion thereof, to form a proportion from about 5% (w/w) form (due to the presence of a co-solvent) at the inter to 40% (w/w), preferably 30% (w/w), more preferably mediate stage, and which Fusidic acid regenerates into 25% (w/w), US 2011/028 1830 A1 Nov. 17, 2011

0110 said acid is selected from a group comprising said cream comprises Fusidic acid made in situ by a conver HCl, H2SO4, HNO3, Lactic acid and the like, either sion of Sodium Fusidate, and a cream base containing at least singly or any combination thereof, to form a proportion one of each of a preservative, a primary and secondary emul from about 0.005% (w/w) to 0.5% (w/w), preferably sifier, a waxy material, a co-solvents, an acid, and water, 0.3% (w/w), more preferably 0.25% (w/w), preferably purified water. 0111 said preservative is selected from a group com 2. A novel dermaceutical cream as claimed in claim 1, prising Methylparaben, Propylparaben, Chlorocresol, wherein said corticosteroid is added from about 0.001% Potassium Sorbate, Benzoic acid and the like, either (w/w) to about 5% (w/w) by weight, preferably from about singly or any combination thereof, to form a proportion 0.005% (w/w) to about 2.00% (w/w) by weight, and most from about 0.05% (w/w) to 0.5% (w/w), preferably preferably from about 0.05% (w/w) to 1.0% (w/w) by weight, 0.3% (w/w), more preferably 0.2% (w/w), and said Fusidic acid is present in an amount from about 0.1% 0112 said buffering agentis selected from a group com (w/w) to about 25% (w/w), preferably from about 0.5% (w/w) prising Di Sodium Hydrogen Ortho Phosphate, Sodium to about 5% (w/w), and more preferably about 2.00% (w/w), Hydrogen Ortho Phosphate and the like, either singly or and in which the amount of said Sodium Fusidate used to any combination thereof, to form a proportion from form in situ said Fusidic acid is in the range between about about 0.01% (w/w) to 1.00% (w/w), preferably 0.5% 0.1% (w/w) to about 25% (w/w), preferably from about 0.5% (w/w), more preferably 0.05% (w/w), (w/w) to about 5% (w/w) and more preferably about 2.08% 0113 said anti-oxidant is selected from a group com (w/w), and prising Butylated Hydroxy Anisole. Butylated Hydroxy said preservatives is selected from a group comprising Toluene and the like, either singly or any combination Methylparaben, Propylparaben, Chlorocresol, Potas thereof, to form a proportion from about 0.001% (w/w) sium Sorbate, Benzoic acid and the like, either singly or to 5% (w/w), preferably 0.1% (w/w), more preferably any combination thereof, to form a proportion from 0.01% (w/w), about 0.05% (w/w) to 0.5% (w/w), preferably 0.3% 0114 said chelating agentis selected from a group com (w/w), more preferably 0.2% (w/w), prising Disodium EDTA and the like, either singly or said primary and secondary emulsifier is selected from a any combination thereof, to form a proportion from group comprising Cetostearyl alcohol, Cetomacrogol about 0.01% (w/w) to 1% (w/w), preferably 0.5% (w/w), 1000, Polysorbate-80, Span-80 and the like, either sin more preferably 0.1% (w/w), and gly or any combination thereof, to form a proportion 0115 said humectant is selected from a group compris from about 1% (w/w) to 15% (w/w), preferably 15% ing Glycerin, Sorbitol, Propylene glycol and the like, (w/w), more preferably 14.5% (w/w), either singly or any combination thereof, to form a pro said waxy material is selected from a group comprising portion from about 5% (w/w) to 40% (w/w), preferably White soft paraffin, Liquid Paraffin, Hard paraffin and 30% (w/w), more preferably 25% (w/w), and the like, either singly or any combination thereof, to 0116 said water in the amount in the range of 20% form a proportion from about 5% (w/w) to 20% (w/w), (w/w) to 75% (w/w), preferably 35% (w/w) to 50% preferably 15% (w/w), more preferably 12.5% (w/w), (w/w), more preferably 40% (w/w) to 43% (w/w), pref said co-solvent is selected from a group comprising Pro erably purified water. pylene Glycol, Hexylene Glycol, PolyEthylene Glycol 0117. It is evident from the foregoing description that the 400 and the like, either singly or any combination present invention has the following distinctions and advan thereof, to form a proportion from about 5% (w/w) to tages over the commercially available comparable products: 40% (w/w), preferably 30% (w/w), more preferably 0118. It has been prepared using Sodium Fusidate 25% (w/w), which is more stable than Fusidic acid said acid is selected from a group comprising acids such as 0119. It has a more stable and quality enriched Fusidic HCl, H2SO4, HNO3, Lactic acid and the like, either acid as the final API singly or any combination thereof, to form a proportion 0.120. The Fusidic acid in the present invention from about 0.005% (w/w) to 0.5% (w/w), preferably degrades more slowly than the conventional products 0.3% (w/w), more preferably 0.25% (w/w), and I0121. The stability level of the Fusidic acid in the water in the amount in the range of 20% (w/w) to 75% present invention remains within the acceptable limits (w/w), preferably 35% (w/w) to 50% (w/w), more pref throughout the shelf life of the product erably 40% (w/w) to 43% (w/w), preferably purified 0.122 The particle size of the Fusidic acid is finer and Water. overall particle distribution in the cream is better, thereby providing better dermaceutical efficacy 3. A novel dermaceutical cream as claimed in claim 2 0123. While the above description contains much speci which further comprises a buffering agent, wherein said buff ficity, these should not be construed as limitation in the scope ering agent is selected from a group comprising Di Sodium of the invention, but rather as an exemplification of the pre Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phos ferred embodiments thereof. It must be realized that modifi phate and the like, either singly or any combination thereof, to cations and variations are possible based on the disclosure form a proportion from about 0.01% (w/w) to 1.00% (w/w), given above without departing from the spirit and scope of the preferably 0.5% (w/w), more preferably 0.05% (w/w). invention. Accordingly, the scope of the invention should be 4. A novel dermaceutical cream as claimed in claim 3 determined not by the embodiments illustrated, but by the which further comprises an anti-oxidant, wherein said anti appended claims and their legal equivalents. oxidant is selected from a group comprising Butylated Hydroxy Anisole. Butylated Hydroxy Toluene and the like, 1. A novel dermaceutical cream containing at least one either singly or any combination thereof, to form a proportion corticosteroid, and Fusidic acid which is made in situ under from about 0.001% (w/w) to 5% (w/w), preferably 0.1% oxygen-free environment using Sodium Fusidate, wherein (w/w), more preferably 0.01% (w/w). US 2011/028 1830 A1 Nov. 17, 2011

5. A novel dermaceutical cream as claimed in claim 4 between about 0.1% (w/w) to about 25% (w/w), prefer which further comprises a chelating agent, wherein said ably from about 0.5% (w/w) to about 5% (w/w) and most chelating agent is selected from a group comprising Diso preferably about 2.08% (w/w), dium EDTA and the like, either singly or any combination said primary and secondary emulsifier is selected from a thereof, to form a proportion from about 0.01% (w/w) to 1% group comprising Cetostearyl alcohol, Cetomacrogol (w/w), preferably 0.5% (w/w), more preferably 0.1% (w/w). 1000, Polysorbate-80, Span-80 and the like, either sin 6. A novel dermaceutical cream as claimed in claim 5 gly or any combination thereof, to form a proportion which further comprises a humectant, wherein said humec from about 1% (w/w) to 15% (w/w), preferably 15% tant is selected from a group comprising Glycerin, Sorbitol, (w/w), more preferably 14.5% (w/w), Propylene glycol and the like, either singly or any combina said waxy material is selected from a group comprising tion thereof, to form a proportion from about 5% (w/w) to white soft paraffin, liquid paraffin, Hard paraffin and the 40% (w/w), preferably 30% (w/w), more preferably 25% like, either singly or any combination thereof, to form a (w/w). proportion from about 5% (w/w) to 20% (w/w), prefer 7. A novel dermaceutical cream as claimed in claim 6 ably 15% (w/w), more preferably 12.5% (w/w), wherein sodium fusidate is converted in-situ under totally said co-solvent is selected from a group comprising Pro oxygen free environment by slow addition of an acid, into pylene Glycol, Hexylene Glycol, PolyEthylene Glycol Fusidic acid of a molecular dispersion form (due to the pres 400 and the like, either singly or any combination ence of a co-solvent) at the intermediate stage, and which thereof, to form a proportion from about 5% (w/w) to Fusidic acid regenerates into an extremely finely dispersed 40% (w/w), preferably 30% (w/w), more preferably form when added to a final cream base, thereby resulting in a 25% (w/w), finely and homogeneously dispersed Fusidic acid in the final said acid is selected from a group comprising HCl H2SO4. cream; all operations of converting sodium fusidate into HNO3, Lactic acid and the like, either singly or any Fusidic acid carried out preferably in an environment free of combination thereof, to form a proportion from about atmospheric oxygen. 0.005% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), 8. A novel dermaceutical cream as claimed in claim 7 more preferably 0.25% (w/w), wherein said conversion of Sodium Fusidate into said Fusidic said preservative is selected from a group comprising acid and the following formation of said Fusidic acid in a Methylparaben, Propylparaben, Chlorocresol, Potas finely dispersed form in the final cream base take place in an sium Sorbate, Benzoic acid and the like, either singly or oxygen-free environment. any combination thereof, to form a proportion from 9. A novel dermaceutical cream as claimed in claim 8 about 0.05% (w/w) to 0.5% (w/w), preferably 0.3% wherein said oxygen-free environment comprises a gaseous (w/w), more preferably 0.2% (w/w), environment formed of inert gas selected from a group com said buffering agentis selected from a group comprising Di prising carbon dioxide, nitrogen, helium and the like. Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen 10. A method of treating primary & secondary skin infec Ortho Phosphate and the like, either singly or any com tions and inflammations said method comprising applying of bination thereof, to form a proportion from about 0.01% a cream containing Fusidic acid which is made in situ under (w/w) to 1.00% (w/w), preferably 0.5% (w/w), more oxygen-free environment using Sodium Fusidate, wherein preferably 0.05% (w/w), said cream comprises Fusidic acid made using Sodium Fusi said anti-oxidant is selected from a group comprising date, at least one corticosteroid, a cream base containing a Butylated Hydroxy Anisole. Butylated Hydroxy Tolu preservative, primary and secondary emulsifiers, waxy mate ene and the like, either singly or any combination rials, co-solvents, acids, and water. thereof, to form a proportion from about 0.001% (w/w) 11. A method of treating primary & secondary skin infec to 5% (w/w), preferably 0.1% (w/w), more preferably tions and inflammations said method comprising applying of 0.01% (w/w), a cream as claimed in claim 10, wherein said cream further said chelating agent is selected from a group comprising comprises any of a group comprising a buffering agent, an Disodium EDTA and the like, either singly or any com antioxidant, a chelating agent, and a humectant, or any com bination thereof, to form a proportion from about 0.01% bination thereof. (w/w) to 1% (w/w), preferably 0.5% (w/w), more pref 13. A method of treating primary & secondary skin infec erably 0.1% (w/w), and tions and inflammations said method comprising applying of said humectant is selected from a group comprising Glyc a cream as claimed in claim 12, wherein said corticosteroid is erin, Sorbitol, Propylene glycol and the like, either sin added from about 0.001% (w/w) to about 5% (w/w) by gly or any combination thereof, to form a proportion weight, preferably from about 0.005% (w/w) to about 2.00% from about 5% (w/w) to 40% (w/w), preferably 30% (w/w) by weight, and most preferably from about 0.05% (w/w), more preferably 25% (w/w), and (w/w) to 1.0% (w/w) by weight said water in the amount in the range of 20% (w/w) to 75% said Fusidic acid is present in an amount from about 0.1% (w/w), preferably 35% (w/w) to 50% (w/w), more pref (w/w) to about 25% (w/w), preferably from about 0.5% erably 40% (w/w) to 43% (w/w), preferably purified (w/w) to about 5% (w/w), and more preferably about Water. 2.00% (w/w), and in which the amount of Sodium Fusi date used to form in situ said Fusidic acid is in the range