Tenofovir disoproxil fumarate oral tablet and preparation method thereof

Abstract

The invention relates to a tenofovir disoproxil fumarate oral tablet and a preparation method thereof. Normal-temperature solution (10-30DEG C) is adopted for preparing pregelatinized starch to serve as an adhesive. The pregelatinized starch in a suspension state is capable of wrapping raw materials to some extent to prevent gathering of the raw materials, gelatinization of pregelatinized starch suspension prepared at the normal temperature is avoided, a disintegration function of the starch is reserved, and since an adhesive action is limited, influences on dissolution due to overlarge particle hardness is avoided. Consumption of auxiliary materials is reduced on the basis of keeping similar dissolubility to existing tablets, total tablet weight can be reduced by 20-40% approximately, tablet size is greatly reduced, and accordingly difficulty in swallowing is lowered, and patients can take the tablet more easily.

Description

Technical field [0001] The invention relates to an oral tablet of tenofovir disoproxil fumarate and a preparation method thereof. Background technique [0002] Tenofovir disoproxil fumarate (Tenofovirdisoproxilfumarate) is an ester prodrug of tenofovir, which belongs to a new type of nucleotide reverse transcriptase inhibitor. After oral administration, it is hydrolyzed to tenofovir and then Phosphorylation of cellular kinases produces pharmacologically active metabolite tenofovir diphosphate. The latter competes with 5'-deoxyadenosyl triphosphate and participates in the synthesis of viral DNA. After entering the viral DNA, it lacks 3'-OH groups. Clusters, which leads to blocking of DNA elongation, thereby blocking virus replication. Because of its significant anti-hepatitis B virus and anti-HIV curative effects, no / low drug resistance, and low toxicity to the human body, it has obvious clinical advantages. The dosage used to treat HIV and HBV infection is oral, daily Once, 300...

AI Technical Summary

Problems solved by technology

This property leads to the situation of "collapsing but not dispersing" in the preparation, which reduces the dissolution rate and bioavailability. In view of this situation, the usual solution is to increase the amount of excipients to reduce the contact between raw materials. The current application Tenofovir disoproxil fumarate tablets (Gilead Sciences) took this approach, although the dissolution of its formulations reached a reasonable level, fast dissolution, fasting oral bioavailability reached 25% , but the weight of the tablet increases, and the proportion of active ingredients in the weight of the tablet is only about 45%

In order to prevent unreasonable drug specifications from causing confusion to clinical medication, the State Food and Drug Administration requires that the dosage should be reasonably determined according to the usage and dosage of the drug, generally not less than the minimum single dosage, tenofovir disoproxil fumarate single dosage The dosage is 300mg, and the total weight of oral tablets containing tenofovir disoproxil fumarate 300mg reaches 700mg. If the tablet is too large and heavy, it will cause certain swallowing problems, especially for some such as the elderly and children. Poor compliance with patients with dysphagia

[0004] CN201110141124 solves the problem of dysphagia by preparing tenofovir disoproxil fumarate into dispersible tablet pharmaceutical preparations, but in the production process of dispersible tablets, it is generally required that the raw material drug be micronized, which increases the production process

At the same time, the quality requirements are relatively high, and the quality standard control is difficult, and it uses sodium lauryl sulfate in the formulation process of the preparation, which has irritating effects on the eyes, skin, respiratory system, and mucous membranes, and Tenofovir disoproxil fumarate has a very bitter taste, and it is difficult to mask the taste when prepared into dispersible tablets, and the taste is not good when taken

[0005] CN200810015780 relates to the preparation process of pharmaceutical preparations containing tenofovir disoproxil salt or its pharmacologically active derivatives, although it is mentioned in the specification that tenofovir fumarate pharmaceutical salts can be prepared, accounting for 5%-95% of the total composition (w / w) preparation, but the highest content of tenofovir fumarate pharmaceutical salt in the tablet containing tenofovir fumarate pharmaceutical salt in the embodiment is only 52.63%, and there is no Innovation, only conventional methods are used, and the dissolution of the preparation is not disclosed. After practice, the preparation is prepared by conventional methods. When the content of tenofovir fumarate medicinal salt exceeds 50% (w / w), the dissolution of the drug Will become slow, "collapse without breaking up"

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