Laniesse Delphine, Smith Dale A, Knych Heather K, Mosley Cornelia, Guzman David Sanchez-Migallon, Beaufrère Hugues
Am J Vet Res. 2017 Jun;78(6):677-687. doi: 10.2460/ajvr.78.6.677.
OBJECTIVE To assess rheological properties and in vitro diffusion of poloxamer 407 (P407) and butorphanol-P407 (But-P407) hydrogels and to develop a sustained-release opioid formulation for use in birds. SAMPLE P407 powder and a commercially available injectable butorphanol tartrate formulation (10 mg/mL). PROCEDURES P407 and But-P407 gels were compounded by adding water or butorphanol to P407 powder. Effects of various concentrations of P407 (20%, 25% and 30% [{weight of P407/weight of diluent} × 100]), addition of butorphanol, and sterilization through a microfilter on rheological properties of P407 were measured by use of a rheometer. In vitro diffusion of butorphanol from But-P407 25% through a biological membrane was compared with that of a butorphanol solution. RESULTS P407 20% and 25% formulations were easily compounded, whereas it was difficult to obtain a homogenous P407 30% formulation. The P407 was a gel at avian body temperature, although its viscosity was lower than that at mammalian body temperature. The But-P407 25% formulation (butorphanol concentration, 8.3 mg/mL) was used for subsequent experiments. Addition of butorphanol to P407 as well as microfiltration did not significantly affect viscosity. Butorphanol diffused in vitro from But-P407, and its diffusion was slower than that from a butorphanol solution. CONCLUSIONS AND CLINICAL RELEVANCE But-P407 25% had in vitro characteristics that would make it a good candidate for use as a sustained-release analgesic medication. Further studies are needed to characterize the pharmacokinetic and pharmacodynamic properties of But-P407 25% in vivo before it can be recommended for use in birds.
目的 评估泊洛沙姆407(P407)和布托啡诺 - P407(But - P407)水凝胶的流变学特性及体外扩散情况,并开发一种用于鸟类的缓释阿片类制剂。样本 P407粉末和市售注射用酒石酸布托啡诺制剂(10 mg/mL)。方法 通过向P407粉末中加水或布托啡诺来配制P407和But - P407凝胶。使用流变仪测量不同浓度的P407(20%、25%和30%[{P407重量/稀释剂重量}×100])、布托啡诺的添加以及通过微滤灭菌对P407流变学特性的影响。将25%的But - P407中布托啡诺通过生物膜的体外扩散与布托啡诺溶液的扩散进行比较。结果 20%和25%的P407制剂易于配制,而难以获得均匀的30%P407制剂。P407在鸟类体温下为凝胶,尽管其粘度低于哺乳动物体温下的粘度。25%的But - P407制剂(布托啡诺浓度为8.3 mg/mL)用于后续实验。向P407中添加布托啡诺以及微滤对粘度没有显著影响。布托啡诺从But - P407体外扩散,其扩散速度比布托啡诺溶液慢。结论及临床意义 25%的But - P407具有体外特性,使其成为用作缓释镇痛药物的良好候选者。在推荐其用于鸟类之前,需要进一步研究以表征25%的But - P407在体内的药代动力学和药效学特性。