Process for the preparation of topical formulation
The present invention relates to the process for the preparation of topical formulations of anthraquinone compound. The present invention specifically relates to the process for the preparation of topical formulations of Rhein or Diacerein in the form of ointment, cream, gel and transferosomal gel. The present invention more specifically relates to the process for the preparation of topical formulations of Rhein or Diacerein in the form of ointment, cream, gel comprising the steps of heating, adding, stirring, dissolving and mixing. The present invention also relates to the process for the preparation of topical formulations of Rhein or Diacerein in the form of transferosomal gel comprising the steps of thin film formation, hydration of thin film and transferosomal gel formation. The present invention also relates to the process for the preparation of topical formulations of Rhein or Diacerein in the form of transferosomal gel comprising the steps of dissolving, adding and mixing.
1 . A process for the preparation of rhein transferosomal gel, wherein the process comprises the steps of:
(a) dissolving Rhein in molten surfactant at 60° C., adding a vesicle forming lipid component and a fluidity buffer by continuous mixing at 60° C. until a homogenous mixture is formed,
(b) adding an aqueous phase containing a penetration enhancer and a humectant to step (a) with continuous mixing until small transferosomes are formed with complete rhein entrapment and then homogenizing or sonicating to further reduce the size of said transferosomes, and
(c) adding a pre-swollen thickening agent or gelling agent to step (b) and mixing, and adjusting pH with a pH adjusting agent.
2 . The process for the preparation of Rhein as claimed in claim 1 , wherein the Surfactant is selected from polawax, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or Sorbitan monostearate.
3 . The process for the preparation of Rhein as claimed in claim 1 , wherein the vesicle forming lipid component is a phospholipid, which is soya lecithin, L-a-(distearoyl) lecithin, L-a-(diapalmitoyl) lecithin, L-a-phosphatide acid, L-a-(dilauroyl)-phosphatidic acid, L-a(dimyristoyl) phosphatidic acid, L-a(dioleoyl) phosphatidic acid, DL-a(dipalmitoyl) phosphatidic acid, L-a(distearoyl) phosphatidic acid, L-a-phosphatidylcholines and salts thereof.
4 . The process for the preparation of Rhein as claimed in claim 1 , wherein the fluidity buffer is selected from Cholesterol.
5 . The process for the preparation of Rhein as claimed in claim 1 , wherein the penetration enhancer is selected from propylene glycol; glycerine, isopropyl palmitate, isopropyl myristate, laurocapram, oleic acid, oleyl alcohol, ethoxydiglycol, alkanecarboxylic acids, adipic acid derivatives, ethanol, urea, polyethylene glycol (PEG), dimethylsulfoxide (DMSO), polar lipids, or N-methyl-2-pyrrolidone, diethylene glycol monoethyl ether, calcipotriene, detergents, emollients, ethoxy diglycol, triacetin, benzyl alcohol, sodium laureth sulfate, dimethyl isosorbide, isopropyl myristate, medium chain triglyceride oil (MCT Oil), menthol, isopropyl isostearate, propylene glycol monostearate, lecithin, diisopropyl adipate, diethyl sebacate, oleic acid, ethyl oleate, glyceryl oleate, caprylic/capric triglyceride, propylene glycol dicaprylate/dicaprate, laureth 4, oleth-2, oleth-20, propylene carbonate, nonoxynol-9,2-n-nonyl-1,3-dioxolane, C 7 to C 14 -hydrocarbyl substituted 1,3-dioxolane, 1,3-dioxine, or acetal and nonoxynol-15.
6 . The process for the preparation of Rhein as claimed in claim 1 , wherein the humectant is selected from glycerol, sorbitol, maltitol, polydextrose, triacetin, propylene glycol, polyethylene glycol (PEG) esters including PEG-20 stearate, PEG-40 stearate, PEG-150 stearate, PEG-150 distearate and PEG-100 stearate, alkoxylated alcohols including laureth-12, ceteareth-20, laureth-23, glycereth-7, glycereth-12, glycereth-26, PEG-4, PEG-6, PEG-8, PEG-12, PEG-32, PEG-75, PEG-150, dipropylene glycol, polypropylene glycol, pantothenol, gluconic acid salts.
7 . The process for the preparation of Rhein as claimed in claim 1 , wherein the thickening agent or gelling agent is selected from cellulose, hydroxypropyl cellulose (“HPC”), hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, acacia, alginic acid bentonite, polyvinyl pyrrolidone, magnesium aluminium silicate, carbomer, microcrystalline cellulose, carboxymethylcellulose calcium or sodium, cetostearyl alcohol, ethylcellulose, glycerin, gelatin, guar gum, hydroxypropyl cellulose, maltodextrin, polyvinyl alcohol, povidone, propylene carbonate, propylene glycol alginate, sodium alginate, sodium starch glycolate, starch, tragacanth, stearic acid and xanthan gum.
8 . The process for the preparation of Rhein as claimed in claim 1 , wherein the pH adjusting agent is selected from triethanolamine (TEA), citric acid monohydrate, amine base tromethamine, tetrahydroxypropyl ethylenediamine, diethanolamine, aminomethyl propanol, and/or sodium or ammonium hydroxide.