Studies On Stability Of Chloramphenicol Eye Drops And Pharmacological Effect Of Its Degradation Products

Chloramphenicol was firstly isolated from metabolic products of Streptomyces venezuelae by Ehrlich et al.in 1947,and is now produced through synthesis and can also be used as its palm ester or amber ester.Chloramphenicol is white or yellowish green needle or long lamellar-shaped crystal or crystallized powder with bitter taste,and easily dissolved in methanol, ethanol,acetone,and propylene glycol.It is stable at dry condition and also stable in weak acidic and neutral solutions,and will not degrade even upon boiling,but would lose efficacy with alkali.It was widely used in clinics in the past years due to its broad spectrum,effectiveness and low price,while its toxicity makes it now only be used in serious infections like typhus and meningitis that other antibiotics or sulfonamides can not take effect.However,this product is widely used for treating acute ear and eye infections under which circumstances the toxicity of the drug is no longer a main problem.Chloramphenicol eye drops is now still widely used in clinics,but it is not stable.It lose efficacy before expiry date when its required storage condition be not met during market circulation.So there exists a need for chloramphenicol eye drops that is stable at room temperature and meets CP standard before expiry date.1.Studies on stability of chloramphenieol eye dropsTo address the existing problems with chloramphenicol eye drops,we have made many selections on its formula and added suitable stabilizing agent to increase its stability.We have found the efficacy of chloramphenicol eye drops can be ensured during its life by adopting suitable dosage form and separate packages for solid-liquid or nonaqueous phase-aqueous phase according to the characteristics of chloramphenicol.2.Functions of SH in eye dropsHyaluronic Acid(HA)is a kind of polysaccharide consisting of repeated subunits of N-acetylglucosarnine and D-glucuronate.Currently people had done many profound studies on HA's structure,properties and physiological effects,and put it into more clinical applications.HA's sodium salt,sodium hyaluronate(SH),is a polymer substance widely present in organisms and its solution has very high viscoelasticity.As a non-Nutonian fluid different from other common viscosifiers,its viscosity would decrease significantly with the increase of sheafing stress,therefore it would not cause unpleasant feel in the eyes even if the viscosity of the solution increases.Now SH is added to chloramphenicol eye drops as an adjuvant and gives good clinical results.SH can increase the viscosity of drug solution,reduce drug inflow to mouth and increase comfortable feel without causing stimulation to eyes.It could raise the drug concentration in tear fluids and aqueous humor,and reduce the frequency of administrations,prolong the retention time in the whole eyes and thus enhance the therapeutic effect.3.Pharmacological experiments of diolsChloramphenicol eye drops containing different concentrations of diols,and eye drops of pure diols were prepared and dropped to the eyes of rabbits(50μL).The drug concentraton in tear fluids,aqueous humor,cornea,and blood were checked within 6 hs after administration,neither chloramphenicol nor diols is detected at all blood sampling spots,indicating that at this dosage the eye drops will not cause damage to hematopoietic system.The concentration of chloramphenicol in tear fluids, aqueous humor,and cornea is much higher than that of its metabolic product diols.Achievements of this research;1)Working out several stable preparation formulas,which could address the existing problems with stability.2)Proving that adding SH to eye drops can increase therapeutic effect. 3)The chloramphenicol eye drops with diols within the limit specified in pharmacopeia is administered ocularly in normal dosage would not come into blood and cause damage to hematopoietic system.The results can be used as a reference for the changing of the maximum limit to diols in chloramphenicol eye drops in CP.