Фармацевтичний журнал (Oct 2019)
Development of the composition and production technology of injection medication for intra-articular introduction based on sodiun hyaluronate
Abstract
Osteoarthrosis is the most widespread disease of musculoskeletal system, which leads to different level of disability in 10–30% of cases. The age of the person is one of the key risk factors for the development of such disease. The most effective resolution is a surgery in which joints are replaced, but this method is very risky and expensive especially for elderly people. That is why development of the composition and research in new technological aspects of biotechnological medication is an actual course in pharmacy. The aim of research: development of the composition and production technology of injection solution of hyaluronic acid as sodium hyaluronate for the therapy of degenerate inflammatory disease of articulation. The object of the study is an injection with sodium hyaluronate for intra-articular administration. Evaluation of the test results when choosing the optimal technology for preparing the injection solution was carried out by the visual method (description, transparency), and by the method of rotational viscometry (viscosity). The suitability of the sterilization regime was determined by physicochemical methods (appearance, transparency, viscosity, pH of the solution) and microbiological method (sterility) according to the requirements of SPhU. The quantitative content of sodium hyaluronate was determined by spectrophotometry (SPhU, 2.2.25) using a carbazole reagent. The results of the studies has been developed the optimal composition of the drug based on stabilized sodium hyaluronate by the excipient BDE. The resulting solution in its physical-chemical properties are a clear, highly viscous aqueous solution. The developed composition contains (in %): Sodium hyaluronate with a molecular weight of ~ 2 MDA (in terms of 100% substance) – 1.0; BDE – 0.75; sodium chloride – 0.85; phosphate buffer – up to pH from 5.0 to 8.5; water for injection – up to 100%. The critical parameters of the technological stages for the production of a drug with sodium hyaluronate are determined experimentally. Specific critical parameters are the degassing of a viscous solution, filtration and the conditions of the sterilization mode of the injection solution. It was experimentally established that the optimal parameters for the filtration stage are the use of a Durapore hydrophilic membrane made of polyvinyl difluoride (PVDF), the temperature of the solution is 50 ± 0.5 °C and the use of back pressure mode to reduce the volume wich is filtered per unit time. It was determined that the sterilization mode with saturated steam at a temperature of 121 °C for 8 min is optimal and ensures the quality of the solution in quality criterion of «Sterility». Samples of the experimental series of injection solution, obtained by the developed technology, comply with the requirements of SPhU for drugs for parenteral use according to physical-chemical and biological quality criteria as appearance, transparency, viscosity, pH of the solution, sterility, assay sodium hyaluronate.
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