Preparation And Quality Of Flucloxacillin Magnesium Amoxicillin Granules

Amoxicillin, a semi-synthetic narrow-spectrum antibiotic belonged to the amino penicillins, is often applied in the treatment to Gram-positive or negative bacterial infections with its characteristics of broadspectrum and sensitivity to penicillinase which limits its application. As a semi-synthetic isoxazolyl penicillin, Flucloxacillin is effective to inhibit the drug resistant staphylococcus aureus which could generate the penicillinase for its resistance to the penicillinase. This drug is mainly used to treat the infection resulted from penicillin resistant staphylococcus aureus whereas it is ineffective in the treatment toGram-negative bacterial infection. The antibacterial mechanism of the two drugs referred above is similar to that of penicillin which could interrupt the synthesis of the bacterial cell wall through combining with PBPs. In view ofthis, itis promising to couple the function of inhibiting staphylococcus aureus generating penicillinase with the ability of resisting some Gram-negative bacterial infection by conjugating Amoxicillin with Flucloxacillin.There have been some compound preparations formulated by Amoxicillin and Flucloxacillin Magnesium supplied in markets abroad.According to the rules of "drug registration regulation", this product is belonged to the 3.2 class chemicals. There is a big market demand of Flucloxacillin Magnesium-Amoxicillin granules because of its good advantages for example excellent absorption of oral administration, high safety and wide range in application. Therefore, to meet the need of production and facilitate the selection of drug in clinical, we developed Flucloxacillin Magnesium-Amoxicillin granules and carried out some studies related to its formulation and process, quality control and stability.The prescription and manufacturing technique of Flucloxacillin Magnesium and Amoxicillin Granules:Based on the characteristics of this product,the excipients which are easier to acquire, faster in dissolving and better on solubility are considered more in the design of prescriptions. The optimized formulation is depicted as below: 128g Flucloxacillin Magnesium,125g Amoxicillin,2500g sucrose,180g sodium carboxymethyl cellulose and appropriated amount of 70% ethanol contained 7% povidine are included per 1000 bags.The process is described as below:The materials of the prescription are precisely weighted and uniformly mixed with primary drug. After screening,70% ethanol solution containing 7% povidone is appropriately addedto make soft material which will be sifted and prilled. Then the resulting wet particles are dried under 60℃. After that the dried particles are pelletized while the fines are removed. Finally, followed the determination of the content of the drug, products are packaged by dose. This prescription was certificated by the examination of dissolution rate, the determination of contentand the investigation tests of influence factors(illumination tests, high temperature tests and high humidity tests). The studiescarriedout above demonstrated that the Flucloxacillin Magnesium and AmoxicillinGranules could be feasibly put on industrial production because of its simplicity ofoperation, theproficiency of process, the good stability and the controllable quality.Flucloxacillin Magnesium and Amoxicillin Granules’quality analysis:according to the quality standard of the British Pharmacopoeia 2010 and the relevant provisions of the Chinese Pharmacopoeia 2010 edition. We have done some quality analysis to this product such as content limitation, physical and chemical characteristics, content identification test, relevant material, dissolving degrees, weight difference examination and high performance liquid chromatograph (HPLC) method for the content determination.Methods are quick, easy and comply with relevant standards.Flucloxacillin Magnesium and Amoxicillin Granules’ stability study:according to chemical drug stability research technique guiding principles and the relevant requirements of the appendix in two parts of the 2010 edition Chinese Pharmacopeia. We did some stability research to this product. The results showed that removing the outer packing, this product’s complete index test results had not significantly changed in the conditions of strong light, high temperature and high humidity. The product stimulated listed packaging sample, placed by 40℃±2℃, RH 75%±5% for 6 months and 25℃±2℃, RH 60%±10% long-term tests for 9 months. The index of examination results had no change, neither. The product has basic stable physical and chemical properties. According to the stability study results and the national drug standards of Flucloxacillin Magnesium and Amoxicillin Granules, recommend that this product should be shading and sealing preservation.