Preparation method of levonorgestrel and ethinylestradiol tablets

Abstract

The invention belongs to the field of pharmaceutic preparation technology, and concretely relates to a preparation method of levonorgestrel and ethinylestradiol tablets. The method comprises the following steps: two bulk drugs containing levonorgestrel and ethinylestradiol are dissolved into a solvent, and a binder is also dissolved into the solvent; in a fluidized bed device, spray drying, solid dispersion and one-step granulation are carried out at the same time for a filler, and the three processes are combined into one step for directly preparing granules; granules as well as a disintegrating agent and a lubricating agent of effective quantities are uniformly mixed, tabletting is carried out, and finally coating is carried out in order to obtain the levonorgestrel and ethinylestradiol tablets. The method is advantageous in that prior production processes are substantially simplified, dissolution rate of the finished product is improved, bioavailability of medicines is improved, and content uniformity is better controlled.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a preparation method of levonorgestrel and ethinylestradiol tablets. Background technique [0002] Levonorgestrel and ethinyl estradiol (triple-phase) tablets are a well-used oral contraceptive at present. It has a small dose and has three specifications. The first specification is that each tablet contains 0.125 mg of levonorgestrel and ethinyl estradiol. 0.03mg, the second specification is that each tablet contains 0.075mg of levonorgestrel and 0.04mg of ethinylestradiol, and the third specification is that each tablet contains 0.05mg of levonorgestrel and 0.03mg of ethinylestradiol. Because the dose of levonorgestrel and ethinyl estradiol tablets is very small, the toxic and side effects in the contraceptive process are very small. This product is widely used in Europe and the United States, and is gradually accepted by most people in China. ...

AI Technical Summary

Problems solved by technology

[0003] Levonorgestrel and ethinylestradiol tablets are administered orally, but the drug is an insoluble drug, insoluble in water, insoluble in ethanol, isopropanol, acetone, ethyl acetate and other solvents, and the tablet prepared by conventional preparation technology Has a low dissolution rate and low dissolution rate, resulting in low bioavailability

In addition, it is difficult to control the content uniformity quality index of small and micro-dose preparation products, which has always been a difficulty in the field of preparation technology

[0004] In the preparation of levonorgestrel and ethinylestradiol tablets, the traditional method adopts the method of conventional equivalent increments to mix the raw and auxiliary materials and then granulate and compress the tablets. The dissolution rate and content uniformity are not ideal, and the deviation is relatively large, especially Difficult to mix evenly with such low doses

[0005] CN200910157979.2 discloses a micronized composition containing levonorgestrel, which adopts a micronized method to improve the dissolution effect; this is a very conventional way to increase the dissolution by reducing the fineness of the original drug, but This method needs to use a high-energy-consuming pulverizer, which consumes a lot of energy and loss, and the particle size is uneven and the effect is not ideal.

[0006] CN201110120200.7 discloses a preparation method of solid dispersion levonorgestrel tablets, the method adopts a melting method to prepare levonorgestrel solid dispersion, but this method requires high-temperature melting, and the process operation is unsafe. After melting, cooling and solidification, it needs to be crushed again, which also consumes a lot of energy and is not environmentally friendly; the entire tablet preparation process has many steps and is cumbersome.