Process for preparing pharmaceutical ophthalmic compositions
Pharmaceutical ophthalmic compositions comprising active ingredient(s) such as carbonic anhydrase inhibitor (CAI) or combinations and processes for making such compositions and the use of these compositions in patient populations including pediatric populations. A process for preparing an ophthalmic composition comprising a carbonic anhydrase inhibitor, which comprises a) preparing a slurry comprising a carbonic anhydrase inhibitor and a surfactant; b) preparing a polymer slurry comprising a polymer and water; c) preparing a solution comprising tonicity and preservative agents; d) mixing the polymer slurry of step b and the solution of step c, to form a vehicle concentrate and adjusting pH; e) adding the slurry of step a, to the vehicle concentrate of step d and mixing to homogenize; f) autoclaving the mixture of step e; g) sizing the mixture of step f, under aseptic condition.
1. A process for preparing an ophthalmic composition comprising a carbonic anhydrase inhibitor, which comprises
a) preparing a slurry comprising a carbonic anhydrase inhibitor and a surfactant;
b) preparing a polymer slurry comprising a polymer and water;
c) preparing a solution comprising tonicity and preservative agents;
d) mixing the polymer slurry of step b and the solution of step c, to form a vehicle concentrate and adjusting pH;
e) adding the slurry of step a, to the vehicle concentrate of step d and mixing to homogenize;
f) autoclaving the mixture of step e;
g) sizing the mixture of step f, under aseptic condition;
wherein the process comprises only single stage autoclaving.
2. The process of claim 1 wherein the carbonic anhydrase inhibitor is brinzolamide.
3. The process of claim 1 wherein sizing is carried out by using microfluidizer, ball mill or colloidal mill.
4. The process of claim 1 wherein the polymer is selected from carbomer, hydroxypropylmethylcellulose, polyvinyl alcohol, hydroxyethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyethylene glycol, sodium carboxymethylcellulose, methylcellulose, ethylcellulose, sodium alginate, gelatin, carboxyvinyl polymer or mixtures thereof.
5. The process of claim 1 wherein the surfactant is selected from alkyl aryl polyether alcohol, polyoxyethylene polyoxypropylene polymer, polyoxyethylenesorbitan fatty acid esters, polyoxyethylene hydrogenated castor oils, sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters or mixtures thereof.
6. The process of claim 1 wherein the preservative is selected from benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, chlorobutanol, benzyl alcohol, sodium dehydroacetate, thiomersal or mixtures thereof.
7. The process of claim 1 wherein the tonicity agent is selected from sodium chloride, glycerol, glucose, mannitol, sorbitol or mixtures thereof.
8. A process for preparing an ophthalmic composition comprising a carbonic anhydrase inhibitor, which comprises
a) autoclaving a slurry comprising a carbonic anhydrase inhibitor and a surfactant;
b) aseptically sizing the particles of the dispersed slurry of step a by microfluidizer;
c) preparing a polymer slurry comprising a polymer and water;
d) preparing a solution comprising tonicity and preservative agents;
e) mixing the polymer slurry of step c and the solution of step d to form a vehicle concentrate and adjusting pH;
f) autoclaving the vehicle concentrate; and
g) aseptically adding the slurry of step b to the sterilized vehicle concentrate of step f.
9. The process of claim 8 wherein the carbonic anhydrase inhibitor is brinzolamide.