CN1287797C - Gancilorvir dispersable tablet and its preparation - Google Patents

Abstract

A ganciclovir dispersible tablet and a preparation method thereof. The dispersible tablet contains 62.5% ganciclovir by mass, 10-25% microcrystalline cellulose or calcium hydrogen phosphate and/or starch, 1-10% sodium carboxymethyl starch or low-substituted hydroxypropyl cellulose and/or cross-linked polysaccharide Vinylpyrrolidone or croscarmellose sodium, 0.1-1.4% polyvinylpyrrolidone or hypromellose, 5-15% lactose, 0.5-1.4% magnesium stearate. Its preparation method is to take ganciclovir, microcrystalline cellulose or calcium hydrogen phosphate and/or starch, carboxymethyl starch sodium or low-substituted hydroxypropyl cellulose and/or cross-linked polyvinylpyrrolidone or cross-linked carmellose sodium , sieved and mixed, polyvinylpyrrolidone or hypromellose was made into ethanol aqueous solution, then added to the solid powder for granulation, dried, granulated, magnesium stearate was added to the granules, mixed evenly, and pressed into tablets The dispersible tablet is obtained. The dispersible tablet completely disintegrates within 3 minutes in water, has good dispersion state, rapid drug dissolution, high bioavailability, and is convenient to take. No special equipment is needed for production, and the cost is low.

Description

Ganciclovir dispersible tablet and preparation method thereof

technical field

The invention relates to an antiviral drug ganciclovir dispersible tablet and a preparation method thereof.

Background technique

Ganciclovir is 9-(1,3-dihydroxy-2-propoxymethyl)guanine. The English name is gancicLovir.

Ganciclovir is another broad-spectrum anti-herpes virus drug with high efficiency, low toxicity and strong selectivity developed after Acyclovir. The difference between it and Acyclovir is that there is another Hydroxymethyl, in vitro, is effective against all herpes viruses, including CMV. It inhibits its synthesis by competitively inhibiting viral DNA polymerase and binding to viral DNA to become the termination code of viral DNA, showing antiviral effect. Oral bioavailability of this product is extremely low (6%-9%), but it is convenient to administer because of the oral form, and oral ganciclovir can obtain good effect on the primary prevention of CMV disease in selected patients. Therefore, Ganciclovir capsules have been sold in my country and more than ten countries in the world. It is mainly used for the treatment of cytomegalovirus infection in immunocompromised or deficient patients (including AIDS patients), such as cytomegalovirus retinitis, cytomegalovirus hepatitis or hemorrhagic gastroenteritis, systemic or central nervous system giant cells virus infection etc. Prevention and treatment of cytomegalovirus infection in recipients of organ transplants or after chemotherapy for leukemia. For herpetic encephalitis, intractable genital herpes, and condyloma acuminata that are ineffective after acyclovir treatment, it can be considered as an alternative drug. In addition, it is also used clinically for the treatment of hepatitis B.

At present, there are many studies on the dosage forms of this product abroad, including capsules, injections, and ophthalmic gels. Its capsules, injections and ophthalmic gels are also listed in my country.

Because the single dose of the capsule is relatively large (250mg), the dosage of each dose is relatively large (4 capsules/time), and the capsule can only be swallowed, which brings inconvenience to patients with dysphagia, the elderly and children.

Contents of the invention

The problem to be solved by the present invention is to provide a ganciclovir dispersible tablet which is convenient and flexible to take, can be swallowed, sucked, and dispersed with water, and a preparation method thereof.

The technical scheme provided by the invention is: ganciclovir dispersible tablets, containing 62.5% ganciclovir by mass, 10-25% microcrystalline cellulose or calcium hydrogen phosphate and/or starch, 1-10% carboxylate Sodium starch glycolate or low-substituted hypromellose and/or crospovidone or croscarmellose sodium, 0.1-1.4% polyvinylpyrrolidone or hypromellose, 5-15% lactose, 0.5 -1.4% magnesium stearate, the sum of the mass percentages of each component is 100%.

The preparation method step of this dispersible tablet is:

1. Take 62.5 parts of ganciclovir, microcrystalline cellulose or calcium hydrogen phosphate and/or starch 10-25 parts, sodium carboxymethyl starch or low-substituted hydroxypropyl cellulose and /or 1-10 parts of cross-linked polyvinylpyrrolidone or cross-linked carmellose sodium, sieved and mixed evenly,

2. Take 0.1-1.4 parts of polyvinylpyrrolidone or hypromellose to make an ethanol aqueous solution, then add the solid powder obtained in step 1 to make soft materials, and granulate with a 14-24 mesh sieve.

3rd, dry the granular material obtained in step 2 at 50-60°C for 4-6 hours, and sieve with 14-24 mesh,

The 4th, add magnesium stearate in the granular material that step 3 obtains, mix uniformly, compress tablet and obtain ganciclovir dispersible tablet.

The ethanol solution of polyvinylpyrrolidone or hypromellose is prepared, and the used ethanol is 40-60% by volume ethanol aqueous solution.

Microcrystalline cellulose (Weijing Xianweisu), polyvinylpyrrolidone (K ₃₀ ), lactose, magnesium stearate, calcium hydrogen phosphate, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted-hydroxypropyl cellulose used in the present invention Ls-Hydroxypropyl cellulose is commercially available

Advantages and positive effects of the present invention

The dispersible tablet of the present invention has unique properties such as short disintegration time, good dispersion state, rapid drug dissolution, high bioavailability, and convenient taking, and its production process is the same as that of ordinary uncoated tablets, no special equipment is needed, and the production cost is relatively low. Low, easy to industrialized mass production. The dispersible tablet of the present invention is completely disintegrated and dispersed in water at 15-25°C within 3 minutes, and the particles can pass through No. 2 sieve and dissolve completely in about 10 minutes. It can be seen that ganciclovir dispersible tablets can be prepared by appropriate formulation design.

Detailed ways

Embodiment 1 per 1000 dosage

Ganciclovir 250g

Microcrystalline Cellulose 75g

Low-substituted hydroxypropyl cellulose 25g

Polyvinylpyrrolidone (K ₃₀ ) 5g

Lactose 40g

Magnesium Stearate 5g

Preparation:

Get the ganciclovir, microcrystalline cellulose low-substituted hydroxypropyl cellulose and lactose of the prescribed amount, sieve, mix well, and cross-linked polyvinylpyrrolidone is made into 50g/L aqueous solution, add in the above-mentioned mixture, make soft Material, passed through a 14-mesh sieve, granulated, wet granules were dried at 50-60°C for 4 hours, granulated, added with magnesium stearate, mixed evenly, and pressed into tablets.

Embodiment 2 per 1000 dosage Ganciclovir 250g Calcium hydrogen phosphate 25g microcrystalline cellulose 50g Low-substituted hydroxypropyl cellulose 25g Polyvinylpyrrolidone (K ₃₀ ) 5g lactose 40g Magnesium stearate 5g

The preparation method is the same as in Example 1, wherein polyvinylpyrrolidone is formulated into a 30 g/L aqueous solution.

Embodiment 3 per 1000 dosage Ganciclovir 250g starch 10g microcrystalline cellulose 50g Carboxymethyl Starch Sodium 35g Polyvinylpyrrolidone (K ₉₀ ) 5g lactose 45g Magnesium stearate 5g

The preparation method is the same as in Example 1, wherein the polyvinylpyrrolidone is made into a 20 g/L ethanol solution, and a 90% volume ratio ethanol aqueous solution is used as the solvent.

Embodiment 4 per 1000 dosage

Ganciclovir 250g

Microcrystalline Cellulose 60g

Cross-linked polyvinylpyrrolidone 40g (plus 20g inside and outside)

Lactose 42g

Magnesium Stearate 5g

Polyvinylpyrrolidone (K ₃₀ ) 3g

The preparation method is the same as in Example 1, wherein the polyvinylpyrrolidone is formulated into a 10 g/L ethanol solution, and a 40% ethanol aqueous solution is used as the solvent.

Embodiment 5 per 1000 dosage

Ganciclovir 250g

Microcrystalline Cellulose 86g

Cross-linked polyvinylpyrrolidone 25g

Lactose 30g

Hydroxypropyl Cellulose 4g

Magnesium Stearate 5g

The preparation method is the same as in Example 1, wherein the hypromellose is formulated into a 10 g/L aqueous solution.

Embodiment 6 per 1000 dosage

Ganciclovir 250g

Microcrystalline Cellulose 45g

Low-substituted hydroxypropyl cellulose 30g (add 20g inside

10g

Croscarmellose Sodium 25g

Lactose 40g

Polyvinylpyrrolidone (K ₃₀ ) 5g

Magnesium Stearate 5g

The preparation method is the same as in Example 1, wherein polyvinylpyrrolidone (K ₃₀ ) is made into a 10 g/L ethanol solution, and a 50% by volume ethanol aqueous solution is used as the solvent.

Embodiment 7 per 1000 dosage

Ganciclovir 250g

Calcium hydrogen phosphate 20g

Starch 35g

Low-substituted hydroxypropyl cellulose 40g (plus 20g inside and outside)

Lactose 45g

Hydroxypropyl Cellulose 5g

Magnesium Stearate 5g

The preparation method is the same as in Example 1, wherein the hypromellose is made into a 10 g/L aqueous solution.

Embodiment 8 per 1000 dosage

Ganciclovir 250g

Microcrystalline Cellulose 25g

Low-substituted hydroxypropyl cellulose 50g

Cross-linked polyvinylpyrrolidone 25g

Lactose 5g

Polyvinylpyrrolidone (K ₃₀ ) 40g

Magnesium Stearate 5g

The preparation method is the same as that in Example 1. Polyvinylpyrrolidone (K ₃₀ ) is made into a 15 g/L ethanol solution, and a 10% volume ratio ethanol aqueous solution is used.

Claims (3)

1, the ganciclovir dispersible tablet is characterized in that, contains following compositions, and each composition quality percent sum is 100%, and the mass percent of each composition is respectively:

62.5% ganciclovir;

The microcrystalline Cellulose of 10-25%, or calcium hydrogen phosphate, or starch, or microcrystalline Cellulose and starch, or calcium hydrogen phosphate and starch;

The carboxymethylstach sodium of 1-10%, or low-substituted hydroxypropyl cellulose, or crospolyvinylpyrrolidone, or cross-linked carboxymethyl cellulose sodium, or carboxymethylstach sodium and crospolyvinylpyrrolidone, or low-substituted hydroxypropyl cellulose and crospolyvinylpyrrolidone, or carboxymethylstach sodium and cross-linked carboxymethyl cellulose sodium, or low-substituted hydroxypropyl cellulose and cross-linked carboxymethyl cellulose sodium;

The polyvinylpyrrolidone of 0.1-1.4% or hypromellose;

The lactose of 5-15%;

The magnesium stearate of 0.5-1.4%.

2, the preparation method of the described dispersible tablet of claim 1 the steps include:

1st, in the described composition content range of claim 1, take off and state composition: (1) 62.5 part ganciclovir; (2) microcrystalline Cellulose of 10-25 part or calcium hydrogen phosphate, or starch, or microcrystalline Cellulose and starch, or calcium hydrogen phosphate and starch; (3) carboxymethylstach sodium of 1-10 part, or low-substituted hydroxypropyl cellulose, or crospolyvinylpyrrolidone, or cross-linked carboxymethyl cellulose sodium, or carboxymethylstach sodium and crospolyvinylpyrrolidone, or low-substituted hydroxypropyl cellulose and crospolyvinylpyrrolidone, or carboxymethylstach sodium and cross-linked carboxymethyl cellulose sodium, or low-substituted hydroxypropyl cellulose and cross-linked carboxymethyl cellulose sodium; (4) lactose of 5-15 part, mix homogeneously then sieves;

2nd, polyvinylpyrrolidone or the hypromellose of getting 0.1-1.4 part is made into ethanol water, adds then in the resulting solid powder of step 1 and makes soft material, granulates with the 14-24 mesh sieve;

3rd, with step 2 resulting granules material at 50-60 ℃ of dry 4-6 hour, with 14-24 mesh sieve granulate;

4th, add the magnesium stearate of 0.5-1.4 part in step 3 resulting granules material, mix homogeneously, tabletting promptly get the ganciclovir dispersible tablet.

3, preparation method according to claim 2 is characterized in that: preparation polyvinylpyrrolidone or hypromellose ethanol water, used ethanol water is the ethanol water of 40-60% volume ratio.