Roxithromycin monohydrate crystal, preparation method thereof and compound dry suspension containing roxithromycin monohydrate crystal and ambroxol hydrochloride composition

Abstract

The invention relates to a roxithromycin monohydrate crystal, a preparation method thereof and a compound dry suspension containing the roxithromycin monohydrate crystal and an ambroxol hydrochloride composition. The roxithromycin monohydrate crystal provided by the invention has a molecular formula of C41H76N2O15.H2O. The preparation method comprises the steps of sample dissolving, devitrifying,smashing, water exchanging and drying. The invention also provides a composition containing the crystal, and the composition comprises 30-70 parts by weight of roxithromycin monohydrate crystals, 5-15 parts by weight of ambroxol hydrochloride, 10-30 parts by weight of xanthan gum, 10-50 parts by weight of hydroxypropyl methylcellulose, 2870-2920 parts by weight of cane sugar and a proper amount of banana essence. The crystal provided by the invention has low moisture absorption and good stability. The composition provided by the invention contains the roxithromycin monohydrate crystal, the suspension is in a good condition, the dissolution rate of medicaments is increased, and the bioavailability is improved.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, in particular to a roxithromycin monohydrate crystal, a preparation method thereof and a composition dry suspension containing the crystal and ambroxol hydrochloride. Background technique

[0002] Pulmonary bacterial infection is a common and frequently-occurring disease of the respiratory system. The main clinical manifestations are cough and expectoration, and antibiotics are usually used for treatment. However, in some cases of bacterial respiratory tract infection with a large amount of sputum, although antibiotics are used reasonably, sometimes the desired curative effect cannot be obtained. The reason may be related to the unobstructed drainage of sputum. The lung is a highly perfused organ. Generally speaking, the concentration of antibacterial drugs in the lung is similar to that in plasma. However, the blood is difficult to perfuse in the abscess cavity and bronchial secretions...

Examples

Embodiment 1

[0063] [embodiment 1] the preparation of roxithromycin monohydrate crystal

[0064] 1) Sample dissolution: under the condition of 40-50°C, dissolve 1 kg of roxithromycin in a mixed solution of 5 kg of anhydrous methanol and 1 kg of acetone to obtain solution I, and keep the temperature of solution I at 38-42° C., wherein;

[0065] 2) Crystallization: Take solution I and press filter to remove insoluble matter to obtain solution II. Keep the temperature of solution II at 38-42°C. Under stirring, continuously add 1 / 4-2 / 5 of the volume of solution II pure water dropwise, and control it at 1 Add within ~2 hours; after crystal growth for 1~2 hours, continue to drop 3 / 5~3 / 4 of the volume of pure water of solution II under stirring, control the addition within 1~2 hours, and stir until crystallization ; After growing crystals for 1-2 hours, cool down to 15-18°C, keep warm for 1-3 hours, centrifuge, and collect the wet product of roxithromycin;

[0066] 3) Pulverization: pulverize th...

preparation Embodiment 1

[0075] [Preparation Example 1] Preparation of Roxithromycin Ambroxol Composition Dry Suspension

[0076] Prescription:

[0077]

[0078]

[0079] Preparation Process:

[0080] 1) The raw and auxiliary materials ambroxol hydrochloride, sucrose, xanthan gum and hypromellose are pulverized through an 80-mesh sieve for subsequent use;

[0081] 2) Take the roxithromycin monohydrate crystals prepared in Example 1 according to the stated amount, mix them with the crushed and sieved raw and auxiliary materials in step 1), add an appropriate amount of banana essence, mix well, and pack it have to.

preparation Embodiment 2

[0082] [Preparation Example 2] Preparation of Roxithromycin Ambroxol Composition Dry Suspension

[0083] Prescription:

[0084]

[0085] Preparation process: same as formulation example 1, the difference is that the roxithromycin monohydrate crystals used are the roxithromycin monohydrate crystals prepared in Example 2.

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, in particular to a roxithromycin monohydrate crystal, a preparation method thereof and a composition dry suspension containing the crystal and ambroxol hydrochloride. Background technique

[0002] Pulmonary bacterial infection is a common and frequently-occurring disease of the respiratory system. The main clinical manifestations are cough and expectoration, and antibiotics are usually used for treatment. However, in some cases of bacterial respiratory tract infection with a large amount of sputum, although antibiotics are used reasonably, sometimes the desired curative effect cannot be obtained. The reason may be related to the unobstructed drainage of sputum. The lung is a highly perfused organ. Generally speaking, the concentration of antibacterial drugs in the lung is similar to that in plasma. However, the blood is difficult to perfuse in the abscess cavity and bronchial secretions...

Examples

Embodiment 1

[0063] [embodiment 1] the preparation of roxithromycin monohydrate crystal

[0064] 1) Sample dissolution: under the condition of 40-50°C, dissolve 1 kg of roxithromycin in a mixed solution of 5 kg of anhydrous methanol and 1 kg of acetone to obtain solution I, and keep the temperature of solution I at 38-42° C., wherein;

[0065] 2) Crystallization: Take solution I and press filter to remove insoluble matter to obtain solution II. Keep the temperature of solution II at 38-42°C. Under stirring, continuously add 1 / 4-2 / 5 of the volume of solution II pure water dropwise, and control it at 1 Add within ~2 hours; after crystal growth for 1~2 hours, continue to drop 3 / 5~3 / 4 of the volume of pure water of solution II under stirring, control the addition within 1~2 hours, and stir until crystallization ; After growing crystals for 1-2 hours, cool down to 15-18°C, keep warm for 1-3 hours, centrifuge, and collect the wet product of roxithromycin;

[0066] 3) Pulverization: pulverize th...

preparation Embodiment 1

[0075] [Preparation Example 1] Preparation of Roxithromycin Ambroxol Composition Dry Suspension

[0076] Prescription:

[0077]

[0078]

[0079] Preparation Process:

[0080] 1) The raw and auxiliary materials ambroxol hydrochloride, sucrose, xanthan gum and hypromellose are pulverized through an 80-mesh sieve for subsequent use;

[0081] 2) Take the roxithromycin monohydrate crystals prepared in Example 1 according to the stated amount, mix them with the crushed and sieved raw and auxiliary materials in step 1), add an appropriate amount of banana essence, mix well, and pack it have to.

preparation Embodiment 2

[0082] [Preparation Example 2] Preparation of Roxithromycin Ambroxol Composition Dry Suspension

[0083] Prescription:

[0084]

[0085] Preparation process: same as formulation example 1, the difference is that the roxithromycin monohydrate crystals used are the roxithromycin monohydrate crystals prepared in Example 2.

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