Cefaclor granule pharmaceutical composition

Abstract

The invention relates to a cefaclor granule pharmaceutical composition, and belongs to the technical field of pharmaceutical preparations. According to the technical scheme, the cefaclor granule composition contains cefaclor, corn starch, cane sugar, sodium carboxymethyl starch, silicon dioxide and hydroxypropyl methylcellulose, and the dosage of the hydroxypropyl methylcellulose and the dosage ofthe sodium carboxymethyl starch are not lower than 9% of the total weight of a unit dose product respectively. The mass ratio of the hydroxypropyl methylcellulose to the sodium carboxymethyl starch is 1: 1, the mass ratio of the sum of the dosages of the hydroxypropyl methylcellulose and the sodium carboxymethyl starch to the cefaclor (anhydrous) is (18-24): (12-16), and the viscosity of the hydroxypropyl methylcellulose is less than 100mPa.S (at 20 DEG C). The invention provides the cefaclor granule pharmaceutical composition which is stable in quality and biologically equivalent to originalresearch.

Description

technical field [0001] The invention relates to a cefaclor granule pharmaceutical composition, which belongs to the technical field of pharmaceutical preparations. Background technique [0002] Cefaclor was developed by Eli Lilly Laboratories, and the trade name is Cefaclor ® (Ceclor ® ), is a second-generation cephalosporin with broad-spectrum antibacterial effect. Its mechanism of action is the same as that of other cephalosporins. It mainly achieves bactericidal effect by inhibiting the synthesis of cell walls. It is sold in many countries around the world, including China, and the product names mainly include Ceclor, Ceclor, Distaclor, kefral, keflor, and Koflor, etc. At present, there are various dosage forms such as dry suspension, capsule, tablet and granule on sale in our country. In February 2018, Xikerao produced by Lilly Suzhou Pharmaceutical Company ® (Cefaclor dry suspension, specification: 0.125g) was selected as the reference preparation for the consistency...

AI Technical Summary

Problems solved by technology

[0004] (1) The vast majority of oral drugs are mainly absorbed in the small intestine, and the absorption site of cefaclor is the upper part of the small intestine, which occupies a very short portion of the total length of the digestive tract, and the location and area of ​​drug absorption are limited

[0005] (2) The drug stability of cefaclor in the body is greatly affected by the pH of the environment. When the pH is greater than 6.0, it will be rapidly degraded, which means that the cefaclor that leaves the upper part of the small intestine will be rapidly degraded, especially when the drug is taken after a meal. The pH of the gastric juice drops sharply, and the alkaline intestinal environment leaves a narrower absorption "window" for cefaclor, making it more difficult to be bioequivalent to the reference preparation

[0006] (3) The physiological characteristics of the human body are very complex, and the pharmaceutical composition may contain a variety of different excipients or have personalized drug physicochemical properties, which may affect the peristalsis rate of the gastrointestinal tract

[0008] Patent CN 103330685 B discloses the use of polyvinyl alcohol-polyethylene glycol graft copolymer dissolved in ethanol to wrap the main drug, and obtains cefaclor granules with good stability and fast dissolution. The disadvantage is that the ethanol solution is used, which gives Industrialized production brings certain potential safety hazards. It is necessary to consider the explosion-proof requirements, and the process requirements are complex. At the same time, because the main drug package is directly mixed with other excipients and then filled to obtain the finished cefaclor granules, the particle size of the finished product is theoretically It is difficult to meet the particle size requirements of the general rules of the Pharmacopoeia for granules (the sum of the number that cannot pass through the No. 1 sieve and the No. 5 sieve does not exceed 15%); patent CN 103623412 B discloses a method that uses diethylene glycol monoethyl ether and colloidal Silica is melted to form a solid dispersion, and the preparation method of cefaclor tablets, which is dry granulated and tabletted with other raw materials, solves the incompatibility between the main drug and the lubricant, and effectively improves the product. Dissolution, the disadvantage is that the granulation process needs to use melting technology, the process is complicated and the cost is high; the patent application CN 108743547 A discloses the use of a specific proportion of polyethylene glycol to dissolve in ethanol and then wrap the main drug, which has good stability. , The fast-dissolving cefaclor granule product, like the patent CN 103330685 B, has the risk of explosion-proof production using organic reagent ethanol, and the vacuum drying step adopted increases the complexity of the process and prolongs the production time, which is not conducive to cost control

[0009] According to the national published reference preparation Hekerao ® (Cefaclor dry suspension, specification 0.125g) quality analysis, its stability under accelerated conditions (40°C±2°C / 65%±5%RH) The dissolution rate of the sample decreased sharply with the prolongation of the investigation time, Indicates that there are potential adverse effects such as decreased bioavailability and decreased drug efficacy. ® Therefore, the storage temperature is required to be below 20°C; the test also found that the dissolution rate of cefaclor granules with different prescriptions also has stability problems during storage.

[0010] Cefaclor granule is a unique dosage form in my country, and there is no reference to the prescription of the reference preparation. In order to solve the above problems, it is necessary to independently design the prescription and process, and there are many combinations of excipients and preparation processes that can be used for the drug. The release and absorption environment of the drug in the body The complexity and the synergy and antagonism between excipients make it difficult for those skilled in the art to easily derive prescriptions and processes that meet the requirements (such as bioequivalence) based on a limited number of trials or brainstorming analysis. Inventors had to expend creative effort to discover the appropriate combination with the desired properties

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