Quality Standard Study Of Sodium Hyaluronate Eeye Drops And Production Management Of Eye Drops

Sodium hyaluronate is a kind of endogenous polymeric glycosaminoglycan existed in animal tissues. Due to its high viscoelasticity and moisture, promoting corneal repairment function, Sodium hyaluronate eye drops (SHED) has been applied widely in clinical for the ophthalmology treatment of Sjogren’s syndrome, Stevens-Johnson syndrome and dry eye syndrome, or external eye diseases made by surgery, drugs, traumatic, wearing contact lenses. As a representative eye drops, SHED is characteristic in its production process as well as unique in its quality control methods. In this paper, quality standards of SHED and production management of dye drops were introduced, which may be helpful for process and quality control of other eye drops.The quality standards of SHED in China were introduced at first, including import standards, enterprise registration and proposed China pharmacopoeia standard draft (2015edition). Full inspection reports of3batches of commercially available SHED products were then conducted as an example. Quantification of benzalkonium chloride was further selected as an illustration example. A HPLC method was established for the determination of benzalkonium chloride in SHED. A Develosil C8-5(4.6i.d.250mm) column was applied; the mobile phase was consisted of acetonitrile (A)-triethylamine perchlorate test solution (7:3; pH2.5)(B); a PDA detector was applied, with the detection wavelengths setting at210nm; the flow rate and column temperature was set at1.0mL/min and40℃癈, respectively; sample volume was50μL. In this condition, trailing factor is not higher than1.3, with the theoretical plate number higher than7000. As a result, the linear range for benzalkonium chloride was between0.015-0.045mg/ml, with the average recovery to be99.3%. The average content of benzalkonium chloride in3batches of SHED was determined to be29.93μg/ml.As for its production, eye drops was recommended as sterile products in China pharmacopoeia (2010edition) for the first time. An implementation of GMP specification (2010edition) required aseptic drug production management of eye drops in sequence. This study discussed the aseptic production process control of eye drops, according to the non final sterilization rules of aseptic production process. The whole process control should be mentioned, including the production workshop cleanliness, sterile operation, material, equipment and facilities, media fills and pragmatic constraints, feeding, content control, environmental monitoring and so on. These results can provide critical factors for the production of eye drops to meet the new GMP standard regulation requirements in the near future.