Optimization and evaluation of the thermosensitive gel formulation of bupivacaine-polydeoxyribonucleotide
Objective:To optimize the temperature-sensitive gel formulation of bupivacaine hydrochloride and polydeoxyribonucleotide in order to obtain analgesic and healing-promoting temperature-sensitive gel preparations with stable quality,appropriate indexes,and long-term release.Methods:The single factor method was employed to investigate the effects of poloxamer 407,poloxamer 188,and sodium chloride on the gelation temperature and time.The range of factors were preliminarily determined.And the star point design response surface method was used to investigate the influence of factor combinations on the gelation temperature and in vitro release.The prescription was optimized,and a series of quality evaluations were conducted.Result:The mass fractions of poloxamer 407,poloxamer 188,and sodium chloride in the optimal prescription determined by the star point design response surface method were 17.468％,3.233％,and 0.519％,respectively.The drug loaded thermosensitive gel prepared by the optimal formulation is a colorless transparent solution.The gelling temperature is(31.33±0.24)℃,the gelling time is(55±7.07)s,the pH value is(5.52±0.01),the viscosity at 4 ℃ is(185.2±13.53)mPa·s,and the viscosity at 25 ℃ is(574.8±14.53)mPa·s.The injectable performance and water-holding capacity were good,and in vitro release studies have shown that the prescription could effectively delay the release rate of the drug and prolong the drug release time to more than 72 h.The open wound test confirmed that the sample could significantly increase the healing rate of wounds in rats and improve the pain sensation of rats after surgery.Conclusion:The optimal prescription selected through single factor method and star point design effect surface method meets the requirements for all measurement indicators,which is expected to be applied in clinical practice.
bupivacaine hydrochloridepolydeoxyribonucleotidestemperature sensitive hydrogelstar point designquality evaluation
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