The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets

Context: Mini-tablets are compact dosage forms, typically 2–3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.

Objective: To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.

Methods: The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL? K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.

Results and Discussion: Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.

Conclusion: This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.     

Bioconversion of hydrocortisone to prednisolone by immobilized bacterial cells in a two-liquid-phase system

Bioconversion of hydrocortisone to prednisolone by free, immobilized and reused immobilized cells of three bacterial strains (Bacillus sphaericus ATCC 13805, Bacillus sphaericus SRP III and Arthrobacter simplex 6946) in an aqueous and a two-liquid-phase system using different organic solvents was investigated. The experiments were carried out in a 125 cm³ shake flask at 27±2°C, 220 rpm for 96 h. The contents of prednisolone and hydrocortisone in samples taken at 0, 3, 6, 24, 48, 72, 96 and 144 h were determined by HPLC analysis. The immobilized bacterial cells showed higher prednisolone yield than the free form in an aqueous system. In the two-phase systems, the butyl acetate to aqueous media ratio of 1: 30 for all three bacterial strains in immobilized forms gave the highest prednisolone yields, at an incubation time of 144 h, of 87·6, 70·6 and 88·3% respectively. For an n-decane to aqueous ratio of 1: 6, moderate prednisolone yields of 81·8, 47·9 and 71·4% were obtained with shorter incubation times of 72, 96 and 6 h respectively. For cyclohexane and other alcohols, the organisms produced low yields of prednisolone (0–30%). Single reuse of all three immobilized bacterial cells gave a 3–20% lower yield of prednisolone than the non-reused cells. The increase in hydrocortisone concentration decreased the prednisolone production whereas increasing the n-decane to aqueous ratio from 1: 6 to 1: 3 caused no significant change in the productivity. © 1998 Society of Chemical Industry     

海普林治疗颜面再发性皮炎118例疗效观察

目的对比观察海普林乳膏与尤卓尔乳膏对颜面再发性皮炎的治疗效果。方法外涂膏剂,辅以口服维生素类药物。结果海普林乳膏组(治疗组)80例,总有效率93.8%,尤卓尔乳膏组(对照组)38例,总有效率68%;经卡方检验,两组疗效有显著性差异。结论治疗组效果优于对照组,海普林乳膏对治疗颜面再发性皮炎患者安全有效。     

氢化可的松母液错流萃取行为研究

将氢化可的松母液解析为氢化可的松、表氢化可的松和６α－羟基ＲＳ三种组分，模拟了母液的表观分配系数。拟合结果与实验值符合较好，平均相对误差＜５．５％。     

液相色谱-串联质谱法测定饲料中氢化可的松

目的 建立液相色谱-串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)测定饲料中氢化可的松含量的分析方法.方法 饲料样品中的氢化可的松经甲醇提取、石墨化碳黑固相萃取柱结合氨基固相萃取柱净化,配制基质匹配标准溶液,外标法定量.色谱采用乙腈(A)和0...     

Formulation Compatibility of Myristyl Nicotinate with Drugs Used to Treat Dermatological Conditions Involving an Impaired Skin Barrier

A number of dermatology conditions including skin photodamage, atopic dermatitis, and rosacea involve skin barrier impairment and first line therapies for these conditions including retinoids and steroids further impair skin barrier function. We have evaluated the compatibility of myristyl nicotinate, an agent that enhances skin barrier function, with drugs used to treat conditions where skin barrier impairment is present including photodamage (retinoic acid), atopic dermatitis (hydrocortisone, triamcinolone acetonide), rosacea (metronidazole), and seborrheic dermatitis (ketoconazole). Myristyl nicotinate was found to be compatible with each of the drugs examined when formulated together and also was shown to be photocompatible with retinoic acid. Our results suggest that the combination of myristyl nicotinate with these drugs is a feasible therapeutic development strategy.     

Imparting recognition sites in poly(HEMA) for two compounds through molecular imprinting

So far, molecularly imprinted polymers (MIPs) have been synthesized and evaluated as selective matrices for single components. It may be possible to impart multiple recognition sites in MIPs, which could be used as elements capable of binding more than one component. Such systems could advantageously be used in the design of sensors having the ability to sense more than one compound at a time. This communication discusses such a possibility by imprinting sites for two model compounds, namely, salicylic acid and hydrocortisone in poly(2‐hydroxy ethyl methacrylate). © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 1823–1826, 1999     

用离心萃取器连续逆流提取氢化可的松的研究

采用环隙式离心萃取器进行了提取氢化可的松的研究。用醋酸丁酯从发酵液中萃取氢化可的松 ,其传质过程受扩散因素控制 ,且分配系数随平衡水相浓度的增大而增大。开发了用环隙式离心萃取器连续逆流提取氢化可的松的工艺流程 ,当转速为 340 0～ 380 0r/min ,总流量为 40～ 75mL/min ,V(O ,有机相 )∶V(A ,水相 )为 (0 35～ 0 42 )∶1 0 0时 ,氢化可的松的萃取率为91 0 8%～ 93 16 % ,而厂家现行生产工艺采用的V(O)∶V(A)是 0 7∶1 0 ,氢化可的松的萃取率为90 %。因而 ,新工艺提高了氢化可的松的萃取率 ,降低了萃取剂耗量     

皮质醇纯物质中杂质分析与定值

皮质醇是临床医学和药物学研究中的重要测定指标,但皮质醇测定的量值溯源问题尚待解决。本工作对皮质醇纯品中杂质的定性定量以及纯度的测定进行了研究。采用HPLC-IT-TOF对与主成分结构类似的杂质进行定性分析,并采用HPLC-MS/MS对杂质含量进行定量测定。采用卡尔费休库仑法、顶空气相色谱法、电感耦合等离子体质谱法对其他杂质进行定量分析,用质量平衡法计算皮质醇纯品的纯度,结果为99.18%,扩展不确定度为U=0.18% (k=2),并用定量核磁法对测定结果进行了验证。结果表明,两种方法定值结果的一致性较好,说明所建立的定性及定量方法准确可靠,对激素类及其他有机纯物质的定性和定量有较好的指导作用。     

Formulation compatibility of myristyl nicotinate with drugs used to treat dermatological conditions involving an impaired skin barrier

A number of dermatology conditions including skin photodamage, atopic dermatitis, and rosacea involve skin barrier impairment and first line therapies for these conditions including retinoids and steroids further impair skin barrier function. We have evaluated the compatibility of myristyl nicotinate, an agent that enhances skin barrier function, with drugs used to treat conditions where skin barrier impairment is present including photodamage (retinoic acid), atopic dermatitis (hydrocortisone, triamcinolone acetonide), rosacea (metronidazole), and seborrheic dermatitis (ketoconazole). Myristyl nicotinate was found to be compatible with each of the drugs examined when formulated together and also was shown to be photocompatible with retinoic acid. Our results suggest that the combination of myristyl nicotinate with these drugs is a feasible therapeutic development strategy.