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首页> 外文期刊>The Internet Journal of Asthma, Allergy and Immunology >Formulation And Evaluation Of Controlled Release Transdermal Patches Of Theophylline - Salbutamol Sulphate
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Formulation And Evaluation Of Controlled Release Transdermal Patches Of Theophylline - Salbutamol Sulphate

机译：茶碱-沙丁胺醇硫酸盐控释透皮贴剂的研制与评价

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Transdermal formulations containing theophylline and salbutamol sulphate were formulated using hydroxy propyl methyl cellulose. Theophylline was loaded by adsorption with the aid of co-adsorbate, sodium chloride. The formulations were subjected to in vitro release studies and the dose of salbutamol and theophylline were optimized to yield the desired flux. The films were uniform and of 200±40 micron thickness. The in vitro flux of theophylline and salbutamol sulphate from the formulation was 1.22±0.4 mg/hr/sq.cm and 13.36±1.02 mcg/hr/sq.cm respectively. The formulation was subjected for pharmacodynamic studies in guinea pigs. The PCT of guinea pigs increased significantly after 4th hour the same was observed even after 24 hours. Pharmacokinetic studies were carried out in healthy human volunteers. Theophylline was analyzed in saliva and salbutamol in the blood plasma. The Tmax of the drugs was 3 hours and appreciable concentrations of the drugs above their MEC could be analysed even after 12 hours. The half-lives of the drugs were significantly prolonged compared to tablets. There was no signs of erythema or oedema in volunteers on observation for a period of 7 days. INTRODUCTION Theophylline is useful for treatment of asthma in only a fairly narrow plasma concentration range. Patients with a peak level exceeding 20mcg/ml experience toxic concentrations as serious as convulsions, yet asthmatics with a mean steady state concentration less than 5 mcg/ml may obtain little protection from the risk of an attack. Theophylline is also a commonly used drug for the treatment or prevention of recurrent apnea of premature infants. Theophylline kinetics vary greatly among individuals on oral administration and several gastric disturbances are also reported [1]. Salbutamol sulphate and theophylline are administered in combination by oral route to effect the synergistic activity of drugs. The dosage forms with this combination were reported to be performing better than a single drug in most of the patients. But controlled release formulations with both drugs in a single formulation are available only as oral dosage forms. Treatment of ailments using transdermal formulations is effectively in vogue and known to have several advantages over the oral dosage forms. The present work is an attempt to incorporate two drugs in the transdermal formulation and to monitor the release of the drugs to maintain the therapeutic levels. Hence theophylline and salbutamol sulphate were selected, as they undergo first pass metabolism and have short half-lives. The dose of theophylline is quite high for incorporation into a transdermal delivery. To overcome the problem loading high doses of theophylline into the polymeric matrix was also one of the objectives of the study. MATERIALS AND METHODS Hydroxy propyl methyl cellulose (15 cps at 1%w/v in distilled water), polyisobutylene (E-Merck, India ), salbutamol sulphate and theophylline (Astra- IDL Ltd , Bangalore), Polyethylene glycol (PEG-400) and sodium chloride (A.R) (S.D fine chemicals, Bombay) were obtained.Adsorption of theophylline on HPMCAdsorption studies were carried out and the experimental variables were optimized to achieve maximum adsorption of theophylline on the polymer. The influence of presence of electrolyte on extent of adsorption was determined using sodium chloride in different concentrations. Theophylline adsorbed polymer was prepared by placing a known weight of the polymer (200-225micrometer range) in contact with the saturated solution of the drug (in 96%v/v ethanol) containing 0.1% w/v sodium chloride, for a period of about 5 hours. The polymer was then removed by filtration and dried under vacuum at low temperature.Formulation of transdermal films of theophylline and salbutamol sulphateThe drug adsorbed polymers equivalent to 150 mg of theophylline was weighed and dissolved in about 10 ml of water to which 40%w/w (of polymer concentration) PEG-400 & 2.5mg S.S was added stirred at a lo
机译：使用羟丙基甲基纤维素配制含有茶碱和硫酸沙丁胺醇的透皮制剂。通过共吸附物氯化钠的吸附来负载茶碱。对制剂进行体外释放研究，并优化沙丁胺醇和茶碱的剂量以产生所需的通量。膜是均匀的并且具有200±40微米的厚度。制剂中茶碱和硫酸沙丁胺醇的体外通量分别为1.22±0.4 mg / hr / sq.cm和13.36±1.02 mcg / hr / sq.cm。该制剂在豚鼠中进行药效学研究。豚鼠的PCT在第4小时后显着增加，甚至在24小时后也观察到。在健康的人类志愿者中进行了药代动力学研究。分析了唾液和沙丁胺醇在血浆中的茶碱含量。药物的Tmax为3小时，甚至在12小时后仍可以分析其MEC上方的明显浓度。与片剂相比，药物的半衰期显着延长。观察7天后，志愿者中没有红斑或水肿的迹象。简介茶碱仅在相当窄的血浆浓度范围内可用于治疗哮喘。峰值水平超过20mcg / ml的患者经历的毒性浓度与惊厥一样严重，但是平均稳态浓度低于5 mcg / ml的哮喘患者可能几乎没有遭受发作风险的保护。茶碱也是治疗或预防早产儿反复呼吸暂停的常用药物。口服茶碱的个体间茶碱动力学差异很大，并且还报道了几种胃病[1]。硫酸沙丁胺醇和茶碱通过口服途径联合给药，以实现药物的协同活性。据报道，在大多数患者中，具有这种组合的剂型表现优于单一药物。但是两种药物在单一制剂中的控释制剂只能以口服剂型获得。使用经皮制剂治疗疾病有效地流行，并且已知与口服剂型相比具有多个优点。当前的工作是试图将两种药物掺入透皮制剂中并监测药物的释放以维持治疗水平。因此，选择了茶碱和硫酸沙丁胺醇，因为它们经历了首过代谢并且半衰期短。茶碱的剂量对于掺入透皮递送是相当高的。为了克服将高剂量茶碱装载到聚合物基质中的问题，也是研究的目的之一。材料与方法羟丙基甲基纤维素（在蒸馏水中1％w / v时为15 cps），聚异丁烯（印度E-Merck），硫酸沙丁胺醇和茶碱（班加罗尔Astra-IDL Ltd），聚乙二醇（PEG-400）茶碱在HPMC上的吸附研究并优化了实验变量以实现茶碱在聚合物上的最大吸附。使用不同浓度的氯化钠确定电解质的存在对吸附程度的影响。通过将已知重量的聚合物（200-225微米范围）与含有0.1％w / v氯化钠的药物饱和溶液（在96％v / v乙醇中）接触一段时间，来制备茶碱吸附的聚合物。大约5个小时。然后通过过滤除去聚合物并在真空下在低温下干燥。茶碱和沙丁胺醇硫酸盐的透皮膜的配制称重相当于150 mg茶碱的药物吸附的聚合物，并将其溶解在约10 ml水中，其中40％w / w （以聚合物浓度计）加入PEG-400和2.5mg SS并在室温下搅拌

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