The Studies On The Lipoic Acid Tablets

Oxidative stress induced by chronic hyperglycemia of diabetic patients is one of the important mechanisms that lead to nerve damage. Neuropathy is prevented and delayed mainly by strict control of blood glucose. However, the patients who have normal blood glucose still occur neuropathy. So the purpose of combating neuropathy can not fully achieve by controlling blood glucose alone. That’s why antioxidants is needed to improve the imbalance of oxidative stress and enhance antioxidant defense capacity. Lipoic acid can achieve its nerve protection function by inhibiting lipid peroxidation, increasing neurotrophic vascular blood flow, improving nerve conduction velocity, increasing the activity of nerve Na+-K+-ATP enzyme, protecting the vascular endothelial and correcting the neuropeptides defects.Lipoic acid, a safe and effective drug for the treatment of diabetic peripheral neuropathy, can improve the clinical symptoms and nerve conduction velocity. In2001, there are more than a dozen pharmaceutical companies producing many kinds of lipoic acid formulations in Germany, including injection, tablets and capsules. The lipoic acid injection (Trade name:Austrian Lippo; Specifications:300mg/12ml) produced by the company of Germany Shi Dade was approved for import by china in2000. However, there is only lipoic acid injection on sale in the domestic market at present. The oral formulations of lipoic acid have not been approved for listing yet. Therefore, the lipoic acid tablets were jointly developed our company and Shandong University to provide more options for patients with diabetes, and improve the compliance of patients.The lipoic acid tablets were made of microcrystalline cellulose, carboxymethyl starch sodium, micronized silica gel, magnesium stearate, and other materials. With the evaluation index of vitro dissolution, the best prescription and production processes were optimized by the method of orthogonal experimental design. The influencing factors, such as the tablet appearance, dissolution, content and the low melting point of lipoic acid, have been taken into account for the tableting process. Finally, the weight of the tablet and the cost of production were reduced, and the preparation process was simplified. The results of three batches showed that the reproducibility and uniformity of the dissolution were good, which may suggest that the prescription is rational and process is stable.Secondly, the related substances in lipoic acid raw materials and tablets were detected by HPLC. The content and the dissolution percentage of lipoic acid tablets were determined by UV-visible spectrophotometry. The appearance of the tablets, identification, weight variation, friability, the degree of quality indicators were studied as well. The quality standards of lipoic acid tablets were established and registered by the State Drug Administration eventually.Finally, the stability tests of lipoic acid tablets, including the impact factor test, accelerated testing and long-term retention test, were conducted. The temperature of high-temperature experiments was selected as25℃and40℃due to the low melting point (60℃～62℃) of lipoic acid tablets. The results showed that related substances of lipoic acid tablets increased obviously after illumination test. The indicators were in line with the provisions after the high temperature test in25℃and40℃. Under conditions of high humidity, the rest of the indicators can meet with the requirements, in addition to the slight gain of weight. So the lipoic acid tablets should be kept in confined, cool dark place. The results of accelerated stability test in6months and the long-term stability test in18months showed that the indicators had no significant changes except for the slight increase of the related substances, compare with the result in0days. So the validity period is tentatively scheduled for12months.Conclusin:The lipoic acid tablets with the filler of microcrystalline cellulose, the disintegrating agent of sodium carboxymethyl starch, and the lubricant of silica powder and magnesium stearate, possess a reasonable prescription and stable product process.