Cidofovir lipid based topical GEL formulation

Abstract

The present invention relates to a topical formulation comprising cidofovir. Particularly, the invention relates to topical lipid based gel formulation comprising cidofovir.

Description

[0001] CIDOFOVIR LIPID BASED TOPICAL GEL FORMULATION

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a topical formulation comprising cidofovir. Particularly, the invention relates to topical lipid based gel formulation comprising cidofovir.

[0004] BACKGROUND OF THE INVENTION

[0005] Cidofovir ((l-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl] cytosine) represents a class of antiviral agent with potent in vitro and in vivo activity against a broad spectrum of herpes viruses. Cidofovir is a nucleotide analogue of deoxycytidine monophosphate that has broad antiviral activity against DNA viruses, including cytomegalovirus, herpes simplex virus, human papillomavirus and molluscum contagiosum.

[0006] Cidofovir is available for intravenous infusion, marketed as VISTIDE for the treatment of Cytomegalic virus retinitis in patients with acquired immunodeficiency syndrome.

[0007] WO2020168358 discloses ointment containing 0.5% to 5% cidofovir in plasticized base or petrolatum and creams containing 0.5% to 5% cidofovir in emollient cream or 1-5% cidofovir in Versabase cream for wounds such as HSV lesions. The formulas have an occlusive character.

[0008] W02013010942 discloses sheet-shaped lyophilized formulation comprising cidofovir, hydroxyethyl cellulose or hydroxypropylmethylcellulose and optionally a plasticizer.

[0009] W02008134033 discloses pharmaceutical formulation comprising 0.0001% - 1% DNA polymerase inhibitor such as cidofovir, wherein said pharmaceutical formulation is a topical dermal pharmaceutical formulation. W02004000359 discloses method of treating warts, comprising topically administering a formulation comprising effective amount of an active agent such as cidofovir, a pharmaceutically acceptable topical carrier, and a permeationenhancing base.

[0010] Toro, Jorge R., et al. (Arch Dermatol; Vol 136, Aug 2000) discloses use of topical Cidofovir for the treatment of Recalcitrant Molluscum Contagiosum in children affected with Human Immunodeficiency Virus 1. Topical gel was compounded by adding 15 ml Vistide in a vehicle.

[0011] Herpes lesions that can be treated with the topical formulations include genital herpes, oral herpes, and shingles. Application of the topical formulation to herpes lesions has been found to reduce the time of healing. In some cases, future outbreaks are prevented or greatly reduced in frequency and / or duration. Application of the topical formulations disclosed herein can prophylactically prevent or reduce the number of outbreaks normally experienced by a person with a herpetic infection.

[0012] Cutaneous warts (or verrucae) are benign skin growths caused by human papillomavirus (HPV). They appear as common warts (on hands and feet), flat warts (face and limbs), or plantar warts (on the soles of the feet) and can be transmitted by touch.

[0013] Systemic administration of an aqueous cidofovir solution, by intravenous injection, possibly leads to systemic side effects. Present therapy i.e., injection (infusion) requires hospital settings and is invasive in nature when used for systemic infection. Cidofovir concentrations need to be increased to assure adequate cidofovir amounts at the target site which may result in nephrotoxicity. On the other hand, local injections of cidofovir at the target site may require multiple injections to assure adequate coverage of the target site. As an alternative to aqueous solutions of cidofovir for injection, creams and ointments have been developed for topical applications, which may assure localized application to the target site. However, the stability of cidofovir in creams is low and its activity therefore deteriorates fast. In addition, the preparation of ointments includes a heating step, which may entail a risk of heat-mediated cidofovir degradation.

[0014] Based on closer review of the prior arts, there appears to be the unmet need of making a topical formulation of Cidofovir with improved characteristics and stability. Therefore, the objective of the present invention is to provide topical lipid based gel formulation of cidofovir which overcomes the drawbacks of the currently known topical formulations.

[0015] SUMMARY OF THE INVENTION

[0016] In one of the aspects of the invention there is provided a topical lipid based gel formulation comprising cidofovir.

[0017] In another aspect of the invention there is provided a topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers.

[0018] In yet another aspect of the invention there is provided a topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers; wherein cidofovir is optionally present in the form of lipid complex.

[0019] DETAILED DESCRIPTION OF THE INVENTION

[0020] The present invention provides a topical lipid based gel formulation comprising cidofovir.

[0021] In one embodiment of the invention, a topical lipid based gel formulation comprises 0.5% w / w - 5% w / w of Cidofovir. Preferably, 1% - 3% w / w of cidofovir. In another embodiment of the invention, there is provided a topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers.

[0022] Penetration enhancers are excipients that can increase skin permeability.Many classes of excipients can be used as penetration enhancers. Suitable lipid based penetration enhancers include soya phosphatidylcholine, phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, cardiolipin, hydrogenated phospholipids, and unsaturated phospholipids. Penetration enhancer of the present invention is present at a concentration of from about 0.2% w / w - 20% w / w.

[0023] Even though the main penetration enhancers of this invention are lipid based penetration enhancers, there could be additional penetration enhancers added in the formulation. Examples of such additional enhancers include, ethers such as diethylene glycol monoethyl ether, diethylene glycol monomethyl ether; surfactants such as sodium laurate, sodium lauryl sulfate, cetyltrimethylammonium bromide, benzalkonium chloride, Poloxamer (231, 182, 184), Tween (20, 40, 60, 80), alcohols such as ethanol, propanol, octanol, benzyl alcohol, and the like; polyethylene glycol and esters thereof such as polyethylene glycol monolaurate; amides and other nitrogenous compounds such as urea, dimethylacetamide (DMA), dimethylformamide (DMF), 2-pyrrolidone, l-methyl-2-pyrrolidone, ethanolamine, diethanolamine and triethanolamine; terpenes; alkanones; and organic acids, such as citric acid and succinic acid, sulfoxides such as DMSO.

[0024] In another embodiment of the invention there is provided a lipid based gel formulation comprising cidofovir and one or more penetration enhancers; wherein cidofovir is optionally present in the form of lipid complex.

[0025] Lipid complex of cidofovir can be prepared by using high pressure / high shear homogenization. In particular, lipid is added in water and dispersed using high shear homogeniser to make uniform dispersion. To this, cidofovir is mixed at high speed till lipid complex having particle size in the nanometre range is achieved. pH of suspension was adjusted to 3.0 to 5.0 using sodium hydroxide. The lipid complex so obtained has particle size in the range of 25 nm to 700 nm.

[0026] The lipid complex obtained by above process is further incorporated into carbopol gel base to prepare the final gel formulation.

[0027] Cidofovir may be present in the formulation as free form (uncomplexed with lipid) or in the lipid complex form. The amount of cidofovir in the lipid complex form may range from 10-50% w / w of total amount of cidofovir present in the formulation.

[0028] Preparation of lipid suspension is a crucial step. Preparation of lipid complex with the help of high pressure / high shear homogenization aids in nanonization of lipid and in turn helps in achieving uniform distribution of lipids in the final gel. Further, when applied to the skin, this helps in increasing the absorption of the active from the skin surface.

[0029] In another embodiment of the invention there is provided a topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers along with pharmaceutically acceptable excipients.

[0030] Suitable pharmaceutically acceptable excipients include gelling agents or gel forming agents, chelating agents, pH adjusters, preservatives / antioxidants, emollients, solubilizers, surfactants and emulsifiers.

[0031] Gel forming agents are substances that are used to impart viscosity or to stabilize the formulations. These may be obtained from natural, synthetic, or semisynthetic sources. Examples include poloxamers, pullulan, polymeric gelling agents such as Acrylic acid-based gelling agents including Carbomers (carbomer 934P, carbomer 940, carbomer 941), Acrylic acid polymers such as Pemulenl polymeric emulsifiers, Cellulose-based gelling agents such as Hydroxypropyl cellulose (HPC), carboxymethylcellulose, and hydroxyethyl cellulose (HEC), natural gelling agents such as Xanthan gum, gellan gum, guar gum, pectin, and gelatin. The gelling agent of the present invention is present at a concentration of from about 0.5 % w / w to 10% w / w.

[0032] The term “chelating agent” as used herein refers to any known pharmaceutically acceptable chelating agents. Suitable chelating agents can include but are not limited to any one or more of ethylenediaminetetraacetic acid (EDTA) and derivatives thereof, ethylene glycol-bis-(2-aminoethyl)-N,N,N',N'-tetraacetic acid (EGTA) and derivatives thereof, cyclohexanediamine tetraacetic acid (CDTA) and derivatives thereof, hydroxyethylethylenediamine triacetic acid (HEDTA) and derivatives thereof, diethylenetriamine pentaacetic acid (DTPA) and derivatives thereof, dimercaptopropane sulfonic acid (DMPS) and derivatives thereof, dimercaptosuccinic acid (DMSA) and derivatives thereof, aminotrimethylene phosphonic acid (ATPA) and derivatives thereof, N,N-bis(carboxymethyl)glycine (NTA) and derivatives thereof, nitrilotriacetic acid and derivatives thereof, citric acid and derivatives thereof, niacinamide and derivatives thereof, sodium desoxycholate and derivatives thereof, polyphosphates; nitrilotriacetic acid, Edetate Calcium Disodium, as well as several simple organic acids like Oxalic acid, Malic acid. Rubeanic acid and Citric acid; and any pharmaceutically acceptable salts thereof. Chelating agent of the present invention is present at a concentration of from about 0.1%w / w - 10%w / w.

[0033] As used herein the term “pH adjuster” refers to any pharmaceutically acceptable formulation, compound, or agent, suitable for adjusting the pH of the presently described topical pharmaceutical formulations without negatively affecting any property thereof. Suitable pH adjusters can include any pharmaceutically acceptable acid or base. Suitable pH adjusters can include but are not limited to hydrochloric acid, sulfuric acid, citric acid, acetic acid, formic acid, phosphoric acid, tartric acid, trolamine, sodium hydroxide and potassium hydroxide. In another embodiment of the invention pH of topical cidofovir formulation is 5 — 8.

[0034] As used herein the term preservative / antioxidant refers to any known pharmaceutically acceptable preservative that functions by inhibiting bacteria, fungi, yeast, mould, other microbe, and / or by inhibiting oxidation. Suitable preservatives include but are not limited to antimicrobial agents and / or antioxidants. Suitable antimicrobial agents can include but are not limited to methyl paraben, propyl paraben, benzoates, benzyl alcohol, sodium benzoate, sorbates, propionates, nitrites, polyethylene glycol 400, hexylene glycol, propylene glycol, benzoic acid, methyl glycol ether, polypropylene glycol 10, glycol ethoxy, capric / polyethylene glycol 6 caprylic glyceride, monobutyl ether ethylene glycol, polyethylene glycol 8 capric / caprylic glycerides, 3 -methoxy-3 -methyl- 1 -butanol, dimethyl isosorbide, Butylated Hydroxy Toluene and mixtures thereof. Suitable antioxidants can include but are not limited to vitamin C, butylated hydroxytoluene (BHT), sulphites, and Alpha tocopherol or vitamin E. Preservative / antioxidant of the present invention is present at a concentration of from about 0.005 % w / w - 10% w / w.

[0035] Emollients are selected from white soft paraffin, fatty acids with 8 to 30 carbon atoms, fatty alcohols with 8 to 30 carbon atoms, fatty acid esters with from 8 to 30 carbon atoms, fatty acid amides with 8 to 30 carbon atoms, including one or more fatty components selected from fatty acids, including capric acid, caprillic acid, lauric acid, medium chain fatty acid (8 to 10 carbons), stearic acid, isostearic acid, octanoic acid, oleic acid, linoleic acid, or linolenic acid, esters of fatty acids, mono- , di- and / or triglycerides of fatty acids, olive oil, sunflower seed oil, coconut oil, cocoa butter, jojoba oil, almond oil, pine needle oil, shea butter, argan oil, nigella sativa oil, beeswax, and flaxseed oil, silicone waxes, soya phosphatidylcholine and mixtures thereof. Emollients are present in the concentration of 5% w / w and above.

[0036] Solubilizer components are selected from polyethylene glycol 400, hexylene glycol, propylene glycol, methyl glycol ether, polypropylene glycol- 10, ethoxydiglycol, capric / caprylic glyceride polyethylene glycol-6, monobutyl ether ethylene glycol, polyethylene glycol-8, capric / caprylic glycerides, 3-methoxy-3-methyl-l-butanol, dimethyl isosorbide and mixtures thereof. Preferably, the water-dispersible component is propylene glycol.

[0037] Surfactants are selected from the monoolein sorbitan / propylene glycol oleate, fatty acid mono- and diglycerides from coconut oil, soy lecithin, egg phosphatide, citric acid esters of mono glycerides, monoglyceride lactic acid esters, sucrose fatty acid esters, oleic acid polyglycolated glycerides, linoleic acid polyglycolated glycerides, fatty acid polyglycerol esters, including both long and medium chain fatty acids and these of polyglyceryl fatty acids of mixed fatty acids, and mixtures thereof. Preferably, the surfactants are polyglycolized glycerides of oleic acids, polysorbate 60 Glyceryl Mono Stearate.

[0038] Emulsifiers are selected from ethylene glycol monostearate, sorbitan tristearate, a mixture of PEG-6 stearate, glycol stearate and PEG stearate and hydrogenated lecithin, ceto stearyl alcohol. Emulsifiers of the present invention is present at a concentration of from about 1% w / w / to 15% w / w.

[0039] In another embodiment of the invention topical lipid based gel formulation comprising cidofovir is subjected to various stability conditions (40°C / 75% RH & 25°C / 60% RH) and evaluated for various parameters such as pH, assay, viscosity and related substances.

[0040] The lipid based gel formulation comprising cidofovir is subjected to in-vitro release testing (IVRT), in-vitro permeation testing (IVPT) and in-vivo clinical studies. These studies would establish the extent of permeation of cidofovir through the skin and there by exhibiting therapeutic efficacy.

[0041] The topical lipid based cidofovir gel formulation may be used for the treatment of herpes infections i.e. Viral Lesions, Plantar Verruca, Genital Warts, Condylomata Acuminata, Molluscum Contagiosum, Vulval Intraepithelial Neoplasia, Extensive disfiguring cutaneous HPV infection on the face in HIV Patients, Resistant hand warts in patient with indolent myelodysplastic syndrome. The topical lipid based cidofovir gel formulation is prepared by a conventional process known in the art.

[0042] The present invention is explained in detail with reference to the following examples described below, which are given for the purpose of illustration only and are not intended to limit the scope of the invention.

[0043] EXAMPLES

[0044] Table 1: Cidofovir lipid based gel formulation (1% w / w and 3% w / w) Process:

[0045] Part-1: Purified water was taken in a vessel. Soya Phosphatidylcholine was added in water and dispersed using high shear homogeniser to make uniform dispersion. To this, cidofovir was mixed at high speed till particle size in nano range is achieved. pH of suspension was adjusted to 3.0 to 5.0 using sodium hydroxide. Part-2: In another vessel, purified water, preservative and / or antioxidant and / or chelating agent was added and mixed properly. To this, gel forming polymer was added slowly with stirring ensuring no lumps formed.

[0046] Part-3. Part-1 was mixed with Part-2 with stirring at sufficient speed to make uniform dispersion. pH of dispersion was adjusted to 5.0 - 8.0 using sodium hydroxide. Final volume was made up to batch size using purified water followed by mixing to make uniform gel.

[0047] Initial characterization data:

[0048] Topical lipid based gel formulation containing 1% w / w cidofovir of Table 1 is characterized for various parameters and the details are as below:

[0049] Table 2: Initial characterization data

[0050] In-vitro release testing: Topical lipid based gel formulation containing 1% w / w cidofovir of Table 1 is evaluated for in-vitro release over a period of 8 hrs. Phosphate buffer pH 7.4 (7ml) was used as the dissolution media and the in vitro release test was carried out using Hanson Franz Diffusion cell at a stirring speed of 600rpm. The release details are as below:

[0051] Table 3: In-vitro release testing results of cidofovir lipid based gel formulation

[0052] Stability studies: Topical lipid based gel formulation of Table 1 is subjected to various stability conditions and evaluated for various parameters such as pH, assay and related substances.

[0053] Table 4: Stability data of topical lipid based gel formulation containing 1% w / w cidofovir at 25°C / 60%RH Table 5: Stability data of topical lipid based gel formulation containing 1% cidofovir at 40°C / 75%RH

[0054] Cidofovir topical formulations disclosed in Table 1 is under testing for in-vitro 5 permeation studies (IVPT) and in-vivo clinical studies as per the following protocols.

[0055] In-vitro permeation testing (IVPT)

[0056] The experiments are being conducted, in-line with the draft guidance on Tn vitro 0 Permeation testing (IVPT) for Topical Drug Products Submitted in ANDAs (Oct

[0057] 2022) published by USFDA, draft guidelines on quality and equivalence of topical products - EMA and USP General Chapter (1724) Semisolid Drug Products - Performance Tests’.

[0058] The method development will be performed to evaluate the pharmacokinetic 5 parameters, Jmax and AMT. The preliminary development will be performed for:

[0059] Selection of Receptor solution: The receptor solution will be selected and validated to maintain sink conditions throughout the duration of the study. The choice of receptor media will also consider compatibility with the skin or membrane and analytical method.

[0060] Selection and Qualification of Membrane (Human Skin): Human skin (typically dermatomed abdominal, back or thigh cadaver skin) will be used for IVPT studies in accordance with regulatory recommendations. Skin storage, preparation, and handling procedures will be standardized.

[0061] Selection of Study Timepoints: Timepoints will be selected to adequately characterize the rate and extent of drug permeation over the course of the study. A minimum of 6-12 timepoints is expected, with justification for selected intervals.

[0062] The study will be performed on the finalized parameters as per the following study design:

[0063] Formulations:

[0064] 1. Test (1 batch of Cidofovir gel 1% w / w) v / s Reference (1 batch of Cidofovir 1% solution)

[0065] 2. Test (1 batch of Cidofovir gel 3% w / w) v / s Reference (1 batch of Cidofovir 3% solution)

[0066] Outcome of the study:

[0067] The cutaneous pharmacokinetic endpoints for the IVPT studies are based upon parameters that characterize the rate and extent to which the drug permeates into and through the skin, and become available in the receptor solution. Specifically, the rate of drug permeation is characterized by the flux (J) and the extent of drug permeation is characterized by the total cumulative amount (AMT) of drug permeated into the receptor solution across the study duration.

[0068] Individual flux (J) and AMT for each cell and donor will be calculated and Jmax and AMT will be inferred.

[0069] Bioequivalence details (for Jmax as well as AMT) shall be provided. In-vivo Clinical study protocol:

[0070] This study is currently ongoing and assesses the efficacy of Cidofovir lipid based topical gel in the subjects with Cutaneous Warts.

[0071] A Multicentre, Double blind, Randomised, Parallel, Active and Placebo Controlled, Phase III Clinical Study to Evaluate Efficacy, Safety and Tolerability of Cidofovir lipid based topical gel in the Subjects with Cutaneous Warts.

[0072] Total 205 subjects were randomised into 3 arms with 2:2: 1 ratio (82 subjects in test arm 1, 82 in test arm 2 and 41 subjects in arm 3 placebo) to get at least 180 evaluable subjects (72 subjects in test arm 1, 72 subjects in test arm 2 and 36 subjects in arm 3 placebo) in India.

[0073] Subjects will be adult males or females with clinical diagnosis of cutaneous warts, must have 2 to 10 clearly identifiable common warts (verruca vulgaris) located on face, hands (dorsal, periungual, or palmar), feet (dorsal), limbs, and / or trunk and meet the following criteria at the baseline visit: a. Each wart must measure 3 to 10 mm in their longest dimension (diameter) on the epidermal plane of the skin at the baseline visit, b. Each wart must be present for at least 4 weeks at the baseline visit, c. Not be covered with hair which, in the investigator’s opinion, would interfere with the study medication treatment or the study evaluations, d. Not be in an intertriginous fold, e. Planter, Subungual and common warts in regions of a pre-existing inflammatory condition or where epidermis is breached are excluded. In addition, other warts (e.g., Anogenital warts) will be excluded.

[0074] The Investigational product (IP) will be applied to the targeted area twice a day for test arms and placebo. IP application demonstration will be done on day of randomization at site.

[0075] Study consists of 8 visits i.e.

[0076] • Visit 1: Screening visit: (Day -14 to Day -1)

[0077] • Visit 2 : Randomisation visit: Week 0 (Day 1)

[0078] • Visit 3 : Follow-up visit: Week 2 (Day 14 + 3 days)

[0079] • Visit 4 : Follow-up visit: Week 4 (Day 28 + 3 days) • Visit 5 : Follow-up visit: Week 8 (Day 56 + 3 days)

[0080] • Visit 6 : Follow-up visit: Week 12 (Day 84 + 3 days)

[0081] • Visit 7 : End of treatment visit : Week 16 (Day 112 + 3 days)

[0082] • Visit 8: Post treatment follow up visit: Week 20 (Day 140 ± 3 days)

[0083] Study duration:

[0084] Approximately total study duration will be 14 days of screening, 16 weeks of treatment period and 4 week post- treatment follow-up period.

[0085] Investigational Product Details:

[0086] Efficacy Assessment:

[0087] Complete clearance of Warts

[0088] Proportion of subjects with total clearance of all warts at 2 week, 4 week, 8 week, 12 week and 16 weeks.

[0089] Clinical examination and photographic documentation of all baseline warts will be performed. Complete clearance is defined as the absence of any visible wart tissue (total disappearance of all visible and palpable wart lesions at the treated sites as recoded with size of 0 mm in the CRF) confirmed by the investigator. Partial clearance of Warts

[0090] Partial Clearance is a noticeable reduction of 50% or morel2 in wart size or number but not full clearance. The proportion of subjects with partial clearance of baseline warts will be assessed at 2 week, 4 week, 8 week, 12 week and 16 weeks. Wart size and number will be measured and recorded at each visit.

[0091] Physician’s Wart Assessment

[0092] Mean change in Physician’s wart assessment (PWA) score from baseline (week 0) to week 2, week 4, week 8, week 12 and week 16. The severity of wart will be assessed using Physician’s Wart Assessment (PWA).

[0093] Physician’s Wart Assessment is a 4 point scale which is as follows:

[0094] 0 = clear, no visible wart,

[0095] 1 = not clear, a visible wart that is less than 3mm in maximal diameter (or length),

[0096] 2 = a visible wart > 3mm and <6 mm in maximal diameter (or length) and

[0097] 3 = a visible wart > 6mm in maximal diameter (or length)

[0098] Change in size of wart

[0099] To compare change in size of wart between the treatment arms at 2 weeks, 4 week, 8 week, 12 week and 16 weeks. Wart dimensions will be measured in two perpendicular diameters (for largest diameter of wart) using calipers or a ruler. Measurements will be recorded consistently by trained personnel.

[0100] Percentage of warts completely cleared

[0101] To compare percentage of warts completely cleared between arms at week 2, week

[0102] 4 week, 8 week, 12 week and 16 weeks. All warts present at baseline and any new warts will be counted at each visit by the investigator.

[0103] Rate of recurrence in subjects with complete clearance

[0104] Percentage of subjects reported with recurrence after complete clearance at the same place till week 20 will be evaluated and compared between the groups.

[0105] Improvement in the Global Aesthetic Improvement Scale score.

[0106] Global Aesthetic Improvement Scale (GAIS) score will be evaluated at week 2, week 4, week 8, week 12 and week 16 to assess overall aesthetic improvement visit in both treatment arms. Investigator will visually inspect the area and judge the overall aesthetic improvement in terms of size and appearance of warts. Improvement is defined as a decrease in diameter of the wart compared to baseline.

[0107] GAIS scoring for individual warts is a 7 point scale which is as follows: very much improved (+3), much improved (+2), improved (+1), no change (0), worse (-1), much worse (-2) and very much worse (-3).

[0108] Note: Wart assessment will be done in similar manner at baseline and subsequent visits preferable by the same evaluator.

[0109] Change of Pain score. The visual analog scale (VAS) is a scale in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of subject’s pain. Each subject will be asked to grade the pain on the VAS, a 10-cm line marked 0 at one end and 10 at the other (0 = no pain; 10 = worst pain imaginable).

[0110] Pain score will be evaluated at baseline visit to week 2, 4, 8, 12 and 16 on drug application.

Claims

CLAIMS:

1. A topical lipid based gel formulation comprising cidofovir.

2. The topical lipid based gel formulation as claimed in claim 1, comprising 0.5% w / w - 5% w / w of Cidofovir.

3. A topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers.

4. The topical lipid based gel formulation as claimed in claim 3, wherein one or more penetration enhancers include soya phosphatidylcholine, pho sphatidylcholine(lecithin) , phosphatidylethanolamine , phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, cardiolipin, hydrogenated phospholipids and unsaturated phospholipids.

5. A topical lipid based gel formulation comprising cidofovir and one or more penetration enhancers; wherein cidofovir is optionally present in the form of lipid complex.

6. The topical lipid based gel formulation as claimed in claim 5, further comprises one or more pharmaceutically acceptable excipients.

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