Abstract

PRODUCT DEVELOPMENT OF OPHTHALMIC ALPHA-2 ADRENERGIC AGONIST SOLUTION

Vikas Thakur* and Shweta Agarwal

Abstract

Glaucoma comprises a group of eye diseases in which a raised pressure inside the eye causes damage to the optic nerve found at the back of the eye, leading to progressive loss of vision. Raised intraocular pressure (above 22mmHg) is a significant risk factor for developing glaucoma. Alpha-2-adrenergic agonist components include chemical entities, such as compounds, ions, complexes and the like, which are effective to act on or bind to alpha-2-adrenergic receptors and provide a therapeutic effect. Results obtained from analytical department gives out sodium chloride content as 0.70% and the total citrate content of 0.530 %, which is total of 0.475% sodium citrate and 0.05% citric acid. Viscosity of the batch was even similar to the innovator sample, i.e. around 3.5 cps. Innovator sample has pH around 6.0 with a solubility of 13 mg/ml and the osmolality was found to be 292mOsm. Solution was clear and greenish yellow in color. Drug X eye drops, is compatible with the TYGON 3350 tubing, when the product is kept in contact with silicone tubing for 36 hrs. Though there is decrease in concentration of preservative to 93.60% but that was within the limit and is tolerable. The Freeze Thaw study was carried out by exposing the product for 48 hours at freezing (-200C) and 48 hours for thawing (300C ± 20C / NMT 25 % RH). There is no difference in results of assay of Drug X and benzalkonium chloride, the assay results for drug X and benzalkonium chloride was found to be 99.00% and 94.60 % respectively. The sample was exposed to photostability test. The assay for the drug in the initial, positive control, dark control and test control were found to be 100%, 100.5%, 99.5% and 100.5% respectively. While the benzalkonium chloride concentration was found to be 99.20%, 98.40%, 97.20% and 98.60% in initial, positive control, dark control and test control samples respectively. From the results of microbiological testing, it was seen that there was more than 1 log reduction in the bacterial and yeast and mould count within 7 days of inoculation. While it further decreased and showed more than 3 log reductions after 14 days and 28 days respectively for both bacteria and yeast and mould. Thus it can be concluded that the preservative is effective even at concentration of 80% of label claim. Drug X eye drops, under test showed water loss up to 2.015% when stored at 40oC and the reference relative humidity of NMT 25% for 3 months. It was observed that the innovator product has average drop size of 34 μL and developed product has 35.75 μL which is almost similar and there is no major variance in drop size. From the stability data, it could be inferred that the 3-month stability data (accelerated 400C ±20C / NMT 25% RH as well as long term 250C ±20C / 40% ± 5%RH) of Drug X eye drops is within accepted limits. Stable formulation for the alpha-2 agonist as ophthalmic solution was developed.

Keywords: DRUG ‘X’.