CN104546902A - Potassium chloride composition freeze-dried tablet and preparation method thereof - Google Patents

Abstract

The invention provides a potassium chloride composition freeze-dried tablet and a preparation method thereof, and relates to the technical field of medicines and medicine production. The potassium chloride composition freeze-dried tablet is prepared from potassium chloride, starch and cane sugar. Starch and cane sugar are used as auxiliary materials, and heating process treatment is performed on the ordinary corn starch, so that the bonding and disintegration functions of starch in the tablet are improved, the formability of the tablet is improved, and the potassium chloride composition freeze-dried tablet only needs the two auxiliary materials namely starch and cane sugar. The potassium chloride composition freeze-dried tablet is prepared by the freeze-drying process that the temperature is increased and decreased for two times; the process that the temperature is increased and decreased for two times enables the formability of the tablet to be better and increases the dissolution rate of the tablet, so as to improve the bioavailability of the tablet; the tablet overcomes the defect of the common potassium chloride, is high in dissolution rate and high in bioavailability, and ensures the curative effect and the safety of the clinical medication; the varieties and the dosage of the auxiliary materials in potassium chloride are reduced.

Description

A kind of potassium chloride composition lyophilizing sheet and preparation method thereof

Technical field

The present invention relates to medicine and medical production technical field, be specifically related to a kind of potassium chloride composition lyophilizing sheet and preparation method thereof.

Background technology

Potassium chloride is clinical conventional electrolyte balance regulating, and clinical efficacy is definite, is widely used in clinical departments.Physical property taste is extremely salty, odorless avirulence.

Molecular formula KC l

Molecular weight 74.55

Potassium chloride tablets, indication is the hypokalemia that 1. treatment hypokalemia a variety of causes cause, as hypoalimentation, vomiting, severe diarrhea, application row potassium diuretic, low potassium familial periodic paralysis, prolonged application glucocorticoid and supplementary hypertonic glucose etc.2. prevent hypokalemia to lose potassium situation when patient exists, if especially occurred when hypokalemia endangers larger to patient (as used the patient of Folium Digitalis Purpureae medicine), need preventative supplementary potassium salt, as little, serious or chronic diarrhea, long-term taking adrenocortical hormone, mistake potassium nephropathy, the Bartter syndrome etc. of taking food.3. digitalism causes frequent, polyphyly premature beat or tachy-arrhythmia.Clinical common formulations is tablet and injection.

In common potassium chloride tablets containing supplementary product kind and quantity more, generally will use filler, lubricant, disintegrating agent, adhesive, correctives etc., its disintegration time reaches 12 minutes, and bioavailability is lower.And increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine.

Therefore, provide one can overcome above-mentioned shortcoming, select suitable adjuvant and technique, reduce supplementary product kind and consumption in potassium chloride tablets, improve potassium chloride tablets bioavailability, ensure that the safety of clinical application all has positive effect.

Traditional lyophilizing tablet can improve bioavailability, but still need use the adjuvant such as mannitol, gelatin.And mannitol has certain biological activity, gelatin resource-constrained and perishable.

Starch is the basic adjuvant of oral solid formulation, it is polymerized by glucose molecule, and be commonly used for adhesive, diluent and disintegrating agent in tablets, it is cheap and easy to get, to human-body safety, but being used alone starch has no report as adjuvant freeze-dry process production potassium chloride lyophilizing sheet.

Summary of the invention

Technical problem to be solved by this invention is the defect overcoming prior art, and propose a kind of potassium chloride composition lyophilizing sheet and preparation method thereof further, said preparation adjuvant is few, good stability, and bioavailability is high.

Technical problem to be solved by this invention realizes by the following technical solutions:

A kind of potassium chloride composition lyophilizing sheet, does adjuvant with starch and sucrose, produces with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common potassium chloride tablets, decreases supplementary product kind and consumption in potassium chloride tablets, and this sheet dissolution is large, bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of potassium chloride composition lyophilizing sheet, is prepared from by following raw material:

A preparation method for potassium chloride composition lyophilizing sheet, comprises step as follows:

A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 4-5, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);

B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution;

The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;

D, take 250 grams, potassium chloride, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring KCE content by E, medicinal liquid, each drug-containing dish dress 1.0ml;

F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain potassium chloride composition lyophilizing sheet.

Described starch selects corn starch, preferably the corn starch solution of 10% (W/V).

Beneficial effect of the present invention is:

The preparation method of a kind of potassium chloride composition lyophilizing sheet of the present invention, heating process process is carried out to common corn starch, starch bonding in tablets, disintegration can be improved, improve the mouldability of tablet, in potassium chloride composition lyophilizing sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Potassium chloride composition lyophilizing sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in potassium chloride composition lyophilizing sheet employing two, and twice cooling, twice intensification can make sheet mouldability better, which increase the dissolution of tablet, thus improve the bioavailability of tablet.

Detailed description of the invention

The technological means realized to make the present invention, creation characteristic, reaching object and effect is easy to understand, below in conjunction with specific embodiment, set forth the present invention further, but following embodiment being only the preferred embodiments of the present invention, and not all.Based on the embodiment in embodiment, those skilled in the art under the prerequisite not making creative work obtain other embodiment, all belong to the protection domain of this patent.

Embodiment 1

A, take the corn starch of 100g, the purified water adding 900ml stirs, and controls 6.5, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 9% (W/V) by pH adjusting agent by the pH value of solution.

B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.

The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.

D, take potassium chloride 250g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring KCE content by E, medicinal liquid, each drug-containing dish dress 1.0ml.

F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain potassium chloride composition lyophilizing sheet.

Embodiment 2

A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 4-5, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 13% (W/V) by pH adjusting agent by the pH value of solution.

B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.

The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.

D, take 250 grams, potassium chloride (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring KCE content by E, medicinal liquid, each drug-containing dish dress 1.0ml.

F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain potassium chloride composition lyophilizing sheet.

Experimental data

The potassium chloride composition lyophilizing sheet that above-described embodiment is obtained carries out following quality research test:

1, hardness, friability contrast test

Get potassium chloride composition lyophilizing sheet prepared by above-described embodiment respectively and potassium chloride ordinary tablet (commercially available) detects friability and hardness by " Chinese Pharmacopoeia " version in 2010 two annex X G inspection techniques, contrast, the results are shown in following table:

Sample	Hardness/N	Friability
			Embodiment 1	65	<1％
Embodiment 2	68	<1％
			Ordinary tablet	70	<1％

Experimental data shows, potassium chloride composition lyophilizing sheet and ordinary tablet without significant difference, meet " Chinese Pharmacopoeia " version in 2010 to the requirement of tablet on friability and hardness.

2, disintegration contrast test

Get potassium chloride composition lyophilizing sheet prepared by above-described embodiment respectively and potassium chloride ordinary tablet (commercially available) operates by Chinese Pharmacopoeia (2010 editions) second annex X A, its disintegration is checked.Result is as follows:

One, potassium chloride ordinary tablet (commercially available)

Two, potassium chloride composition lyophilizing sheet (No. 1 to No. 3 is embodiment 1, and No. 4 to No. 6 is embodiment 2)

Result judges:

Judge about the bioassay standard in disintegration of tablet time limit according to Chinese Pharmacopoeia (2010 editions) second potassium chloride tablets quality standard and Chinese Pharmacopoeia (2010 editions) second annex X A, potassium chloride tablets is no more than 15 minutes for qualified disintegration, actual measurement is 12 minutes, and potassium chloride composition lyophilizing sheet (embodiment 1 and embodiment 2) disintegration is 6 minutes.It can thus be appreciated that potassium chloride composition lyophilizing sheet disintegration is than reducing by 50% (6 minutes) potassium chloride tablets (commercially available) disintegration, so potassium chloride composition lyophilizing sheet absorption of human body is faster, the blood drug level peaking time is shorter than potassium chloride ordinary tablet (commercially available), its bioavailability is higher, better efficacy.

More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.

Claims (2)

1. a potassium chloride composition lyophilizing sheet, is characterized in that, is prepared from by following raw material:

2. a preparation method for potassium chloride composition lyophilizing sheet according to claim 1, is characterized in that, comprise step as follows:

A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 4-5, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);

B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution;

The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;

D, take 250 grams, potassium chloride, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after measuring KCE content by E, medicinal liquid, each drug-containing dish dress 1.0ml;

F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain potassium chloride composition lyophilizing sheet.