盐酸小檗碱肠溶缓释片制剂工艺研究

目的 研究盐酸小檗碱肠溶缓释片的制剂工艺。方法 采用体外释放度评价的方法,以单因素设计及正交设计筛选片芯处方及工艺,并对片芯进行肠溶包衣,制备盐酸小檗碱肠溶缓释片。结果 体外释放度实验显示,片芯及肠溶片均符合Higuchi释药模型。结论 盐酸小檗碱肠溶缓释片工艺稳定,体外释放符合设计要求。     

复方甘草含片的研究进展

复方甘草含片是在复方甘草片基础上的一次剂型改革,将甘草片改进为含片,使其成为味道适宜、质量稳定的新剂型,主要有镇咳、祛痰、消炎作用。通过实践研究发现,复方甘草含片镇咳祛痰的疗效强于复方甘草片。本文通过查阅分析相关文献,从药理作用、临床疗效、制备工艺、质量控制四个方面系统的阐述了复方甘草含片的研究进展及所取得的进步,为其在临床上合理应用进一步提供了依据。     

盐酸益母草碱片的制备及质量评价

目的制备盐酸益母草碱片,并进行质量评价。方法采用湿法制粒技术,以盐酸益母草碱为原料药,采用单因素实验筛选填充剂、崩解剂、黏合剂、润滑剂种类;结合正交实验,以15 min累积溶出度(以水为溶出介质)为指标,筛选崩解剂占比、黏合剂溶液质量分数、润滑剂占比,并进行验证。按2020年版《中国药典》(四部)通则方法对所制盐酸益母草碱片的体外溶出行为(溶出介质分别为pH1.2的盐酸溶液、pH4.5的醋酸-醋酸钠溶液、pH6.8的磷酸盐缓冲液、水)、片剂外观、硬度、脆碎度、含量均匀度进行检测。结果盐酸益母草碱片的最优处方为盐酸益母草碱原料药500 mg、糊精9250 mg、交联聚维酮200 mg、硬脂酸镁50 mg、1%羟丙甲纤维素溶液4 mL。所制3批片剂的平均15 min累积溶出度为81.25%(RSD=1.12%,n=3)。在上述4种溶出介质中,所制片剂均能在30 min内达到溶出平衡,且累积溶出度均超过85%。所制片剂外观颜色均一,呈米黄色,表面光滑,边缘完整,无杂色、斑点、异物等,硬度为57.3 N(n=6),减重率为0.15%,含量均匀度符合2020年版《中国药典》(四部)相关规定。结论成功制备了盐酸益母草碱片,且质量符合相关规定。     

重复经颅磁刺激联合帕利哌酮对精神分裂症患者认知功能的影响

目的探讨重复经颅磁刺激(rTMS)联合帕利哌酮缓释片对精神分裂症患者认知功能的疗效及安全性。方法选择符合入组条件的首发精神分裂症患者61名,随机分成治疗组30例(帕利哌酮缓释片联合rTMS),对照组31例(单纯药物)。分别于治疗前及治疗4周后应用阳性与阴性症状量表(PANSS)评定临床症状;应用数字划消测验(CT)、修订版韦氏记忆量表(WMS-RC)、威斯康星卡片分类测验(WCST)分别评定患者的注意功能、记忆功能及执行功能。结果治疗后,两组PANSS总分均低于治疗前,治疗组总分明显低于对照组(P<0.01);两组CT、WMS-RC各指标的得分均优于治疗前(P<0.01),治疗组明显高于于对照组(P<0.05);治疗组WCST各项评分优于治疗前,对照组总应答数、持续错误数、非持续性错误数较治疗前明显降低(P<0.05);治疗组的总应答数、持续错误数及非持续性错误数明显低于对照组(P<0.05)。两组均未出现明显副反应。结论重复经颅磁刺激联合帕利哌酮缓释片对改善精神分裂症患者的认知功能有增效作用,安全性好。     

Anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D. Adams

The anti-inflammatory activity of hexane leaf extract of Aspilia africana C.D. Adams (Compositae) was evaluated in rodents using the xylene-induced ear edema, egg albumin- and agar-induced paw edema, formaldehyde-induced arthritis, cotton pellet granuloma, gastric ulcerogenic, acetic acid-induced vascular permeability and dextran-induced in vivo leukocyte migration tests. Results showed that the extract (5mg/ear) inhibited topical edema in the mouse ear and at 200 and 400mg/kg (i.p.), it significantly (P<0.05) suppressed the development of egg albumin- and agar-induced paw edema, and the global edematous response to arthritis induced by formaldehyde in rats. Oral administration of the extract (200 or 400mg/kg) evoked a significant (P<0.05) dose-related ulceration of the rat gastric mucosa and inhibition of vascular permeability induced by acetic acid in mice. The extract also significantly (P<0.05) reduced total leukocyte and neutrophils counts in a non-dose-related manner. However, it significantly (P<0.05) increased lymphocyte counts and stimulated the growth of granuloma tissues induced by subcutaneously implanted cotton pellets in rats. Phytochemical tests showed that the extract contained sterols and terpenoids. These findings suggest that the leaves of Aspilia africana possess anti-inflammatory activity in acute and certain aspects of chronic inflammation, which may derive from inhibition of prostaglandins synthesis, inhibition of increased vascular permeability, inhibition of neutrophil migration into inflamed tissues, and stimulation of lymphocyte accumulation, which may enhance tissue repair and healing. The terpenoids present in the leaves may account for the anti-inflammatory activity.     

Determination and Estimation of Pharmacokinetic Profile of Caffeine in Form of Extract of Green Tea Leaves and its Analogy with Synthetic Form

The aim of the study was to formulate and investigate the pharmacokinetic parameters for the tablets of herbal extract of caffeine with comparison to synthetic formulation. The tablets of the aqueous herbal extract of leaves of Camellia sinensis and synthetic caffeine were formulated by wet granulation technique. The HPLC and HPTLC were applied as analytical tools for estimation of caffeine. The batches of formulation (B1 to B7) were subjected for various pre and post-formulation studies. The pharmacokinetic of the batch B5 was assessed in rabbits, and the results were compared to synthetic batch B7. With the suitable pre and post-formulation results, the B5 showed in vitro release of 90.54% of caffeine at the end of 60 min. The release followed first order kinetics and the plot of Higuchi and Peppas confirms anomalous diffusion as the basic mechanism behind the release. B5 revealed non-significant mean C_max, t_1/2, and AUC of 1.88 μg/ml, 5.52 h and 9.67 μg.h/ml respectively compared to B7. The study highlights; no significant difference in the pharmacological effect of caffeine when administered in the form of extract. The administration of herbal extract can further provide the other health benefits lacked by synthetic caffeine.     

Anti-visceral obesity and antioxidant effects of powdered sea buckthorn (Hippophae rhamnoides L.) leaf tea in diet-induced obese mice

The potential health benefits of tea have long been studied. This study examined the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six weeks. SLT suppressed body weight gain in a dose-dependent manner and significantly reduced visceral fat, plasma levels of leptin, triglyceride and total cholesterol and ALT activity compared with the high-fat-fed control mice. SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP, β-oxidation and CPT activities. However, SLT supplementation during high-fat feeding led to a significant decrease in PAP, β-oxidation and CPT activities with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and hepatic and erythrocyte lipid peroxides were significantly lowered with SLT supplements. Hepatic and erythrocyte SOD and CAT activities were also increased with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was increased in erythrocytes only. These results indicate that SLT has potential anti-visceral obesity and antioxidant effects mediated by the regulation of lipid and antioxidant metabolism in high-fat diet-induced obese mice.     

处方工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响

目的 研究处方中的辅料及工艺对瑞舒伐他汀钙片混合均匀度及含量均匀度的影响。方法 采用粉末直接压片工艺，通过单因素试验，考察处方中乳糖的型号、微晶纤维素的型号、乳糖与微晶纤维素的比例、钙盐的种类及交联聚维酮用量对混合均匀度及含量均匀度的影响；同时研究混合工艺对混合均匀度及压片工艺对含量均匀度的影响。结果 不同的乳糖型号（T80、PW80、315）、微晶纤维素型号（PH102、M102、102）、乳糖与微晶纤维素的比例（1:1、3:1、1:3）、钙盐的种类（磷酸钙（细颗粒）、无水磷酸氢钙（细颗粒、细粉）、碳酸钙（细粉））的处方混合均匀度及含量均匀度良好，磷酸钙（粗颗粒）的处方混合均匀度及含量均匀度较差。在混合容器中加入50%的乳糖，之后加入原料药、微晶纤维素、交联聚维酮和磷酸钙，以10 r·min-1混合20~25 min；再加入剩余的乳糖，以10 r·min-1混合15~25 min，物料混合均匀度良好。重力加料器及压片速度（10~20 r·min-1）的含量均匀度良好；强制加料器及压片速度（30 r·min-1）的含量均匀度较差。结论：通过研究筛选出了适合粉末直压工艺的乳糖型号、微晶纤维素型号、乳糖与微晶纤维素比例、钙盐种类及交联聚维酮用量。考察了混合工艺参数范围，优选了重力加料器及压片速度（10~20 r·min-1），获得了良好的混合均匀度和含量均匀度。     

Formulation of multiparticulate systems as lyophilised orally disintegrating tablets

The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality.     

Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

Halken S, Agertoft L, Seidenberg J, Bauer C‐P, Payot F, Martin‐Muñoz MF, Bartkowiak‐Emeryk M, Vereda A, Jean‐Alphonse S, Melac M, Le Gall M, Wahn U. Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.
Pediatr Allergy Immunol 2010: 21: 970–976.
© 2010 John Wiley & Sons A/S The efficacy and safety of five‐grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5–11 yr) and adolescents (12–17 yr) with grass pollen–allergic rhinoconjunctivitis were included in a multinational, randomized, double‐blind, placebo‐controlled study and received either a 300IR five‐grass pollen tablet or placebo daily in a pre‐ (4 months) and co‐seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five‐grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.