Kodym Anna, Wiśniewski Andrzej, Knioła Dawid, Olejniczak Monika
Department of Pharmaceutical Technology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 9 M. Skłodowskiej-Curie St., Bydgoszcz, Poland.
Acta Pol Pharm. 2011 Jul-Aug;68(4):555-64.
The aim of the studies was to develop formulary technologies of 1% and 5% eye drops containing cefuroxime with stability of at least 10-12 days. The stability was defined as the time required to reach the cutoff value of 10% degradation of cefuroxime in the drops, as determined using an HPLC assay. The drops should have such properties as optical clarity, pH in the range of 3.5 to 8.5 and osmotic pressure not lower than 280 mOsm/L. Additionally, drops of enhanced viscosity within the range 7-9 mPaxs were developed. Drops (1% and 5%) were prepared under aseptic conditions by dissolving Biofuroksym (Cefuroxime natricum) IBA Bioton--the form of the drug for dry injections--in citrate buffer of pH 6.05-6.28. Polyvinyl alcohol was used to increase the viscosity of the drops. Phenylmercuric borate at the final concentration of 0.001% was used together with beta-phenylethyl alcohol at the final concentration of 0.4% to preserve the drops. The drops were stored for 30 days in tightly closed glass bottles at the temperature of 4 degrees C and 20 degrees C, protected from light. As the course of the infection may differ in intensity, location and the area of the infection in the eye, the composition of the drops was developed at two concentrations (1% and 5%), and five formulary versions for each concentration were prepared. The concentration of cefuroxime in the drops was determined every three days using HPLC. Such properties as pH, osmotic pressure and viscosity were also examined. Additionally, organoleptic analysis (clarity, color, odor) was performed. Physical and chemical properties of all formulations of 1% and 5% drops containing cefuroxime prepared in citrate buffer of pH 6.05-6.28 met the standards set in the objective of the work. The stability of cefuroxime in buffered drops stored at the temperature of 4 degrees C, determined with HPLC as the time of 10% degradation of cefuroxime, was 15 days for 1% and 5% drops. In the drops, which were buffered and of increased viscosity, the times of 10% cefuroxime degradation were 18 days for 1% drops and 30 days for 5% drops. The preservatives added to the buffered drops did not lower their stability. Osmotic pressure, pH and viscosity of the drops during the period of 30-day-storage at the temperature of 4 degrees C met the requirements acceptable for the eye drops. The stability of 1% and 5% buffered drops containing cefuroxime stored at the temperature of 4 degrees C allows preparing the drops in pharmacies on the basis of doctor's prescription. Depending on the character and the course of the infection the drops can be prepared at the concentration of 1% and 5% following the composition of the selected formulation which would meet the individual needs of the patient's therapy.
这些研究的目的是开发含头孢呋辛的1%和5%滴眼液的处方技术，使其稳定性至少达到10 - 12天。稳定性定义为滴眼液中头孢呋辛降解达到10%的截止值所需的时间，该时间通过高效液相色谱法测定。滴眼液应具备如下特性：光学澄清度、pH值在3.5至8.5范围内以及渗透压不低于280 mOsm/L。此外，还开发了粘度在7 - 9 mPa·s范围内的增稠滴眼液。通过将Biofuroksym（头孢呋辛钠）IBA Bioton（用于冻干注射剂的药物形式）溶解在pH值为6.05 - 6.28的柠檬酸盐缓冲液中，在无菌条件下制备1%和5%的滴眼液。使用聚乙烯醇来增加滴眼液的粘度。最终浓度为0.001%的硼酸苯汞与最终浓度为0.4%的β - 苯乙醇一起用于保存滴眼液。将滴眼液在4℃和20℃的温度下，避光保存在密封玻璃瓶中30天。由于眼部感染的病程在强度、位置和感染区域可能有所不同，因此滴眼液的成分开发了两种浓度（1%和5%），每种浓度制备了五个处方版本。每三天使用高效液相色谱法测定滴眼液中头孢呋辛的浓度。还检测了pH值、渗透压和粘度等特性。此外，进行了感官分析（澄清度、颜色、气味）。在pH值为6.05 - 6.28的柠檬酸盐缓冲液中制备的含头孢呋辛的1%和5%滴眼液的所有制剂的物理和化学性质均符合工作目标中设定的标准。用高效液相色谱法测定，在4℃温度下储存的缓冲滴眼液中头孢呋辛的稳定性，即头孢呋辛降解10%的时间，1%和5%的滴眼液均为15天。在缓冲且粘度增加的滴眼液中，1%的滴眼液头孢呋辛降解10%的时间为18天，5%的滴眼液为30天。添加到缓冲滴眼液中的防腐剂并未降低其稳定性。在4℃温度下储存30天期间，滴眼液的渗透压、pH值和粘度均符合滴眼液可接受的要求。含头孢呋辛的1%和5%缓冲滴眼液在4℃温度下的稳定性使得可以根据医生处方在药房配制滴眼液。根据感染的特征和病程，可以按照所选制剂的成分制备1%和5%浓度的滴眼液，以满足患者治疗的个体需求。
