CN104586780A - Penfluridol oral freeze-dried tablets and preparation method thereof - Google Patents

Abstract

The invention provides penfluridol oral freeze-dried tablets and a preparation method thereof and relates to the technical fields of medicines and medicine production. The penfluridol oral freeze-dried tablets contain penfluridol, starch and cane sugar, wherein starch and cane sugar are used as auxiliary materials; common corn starch is subjected to a heating process treatment so that the adhesion and disintegration functions of starch in the tablets can be improved, and the formability of the tablets can be improved, and the penfluridol oral freeze-dried tablets only need the two auxiliary materials, namely starch and cane sugar. The penfluridol oral freeze-dried tablets adopt a freeze-drying process of cooling twice and heating twice, the formability of the tablets can be better because of cooling twice and heating twice, and the dissolution rate of the tablets is increased, thus improving the bioavailability of the tablets; the tablets overcome the defects of common penfluridol tablets, reduce the types and the dosages of the auxiliary materials in the penfluridol tablets, have a high dissolution rate and a high bioavailability, and ensure the curative effect and the safety of clinical medication.

Description

A kind of penfluridol oral freeze-dried slices and preparation method thereof

Technical field

The present invention relates to medicine and medical production technical field, be specifically related to a kind of penfluridol oral freeze-dried slices and preparation method thereof.

Background technology

Penfluridol is oral depot antipsychotics.Antipsycholic action is relevant with dopamine receptor in its blocking-up brain, also nervous system-adrenoceptor capable of blocking, and antipsycholic action is lasting by force, oral once can maintain a couple of days to one week, Yi You tells effect in town, but sedation is more weak, lighter on cardiovascular function impact.To hallucination vain hope, unsociable and eccentric, indifferent, the symptom such as to shrink back is effective.Be applicable to acute and chronic various schizophrenia, be especially convenient to Long-term taking medicine maintaining treatment, prevent recurrence.

In common Penfluridol Tablet 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 Penfluridol Tablet, improve Penfluridol Tablet 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, 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 the oral freeze-dried compounded plate of adjuvant freeze-dry process production penfluridol.

Summary of the invention

Technical problem to be solved by this invention is the defect overcoming prior art, and propose a kind of penfluridol oral freeze-dried slices 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 penfluridol oral freeze-dried slices, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common Penfluridol Tablet, decrease supplementary product kind and consumption in Penfluridol Tablet, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.

A kind of penfluridol oral freeze-dried slices, is prepared from by following raw material:

A preparation method for penfluridol oral freeze-dried slices, 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 4.5-5.5, 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 100m L, 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 penfluridol 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after surveying penfluridol 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 the oral freeze-dried compounded plate of penfluridol.

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 penfluridol oral freeze-dried slices 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 the oral freeze-dried compounded plate of penfluridol, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.The oral freeze-dried compounded plate of penfluridol only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in the oral freeze-dried compounded plate employing two of penfluridol, and twice cooling, twice intensification can make sheet mouldability better, and shorten the disintegration time of tablet, 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 900m l 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 100m L, 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 penfluridol 10g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring penfluridol 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 the oral freeze-dried compounded plate of penfluridol.

Embodiment 2

A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 4.5-5.5, 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 100m L, 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 penfluridol 10 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.

Medicinal liquid is sub-packed in drug-containing dish after measuring penfluridol 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 the oral freeze-dried compounded plate of penfluridol.

Experimental data

The penfluridol oral freeze-dried slices that above-described embodiment is obtained carries out following quality research test:

1, hardness, friability contrast test

Get the oral freeze-dried compounded plate of penfluridol prepared by above-described embodiment respectively and penfluridol 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	67	<1％
			Ordinary tablet	67	<1％

Experimental data shows, the oral freeze-dried compounded plate of penfluridol 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 the oral freeze-dried compounded plate of penfluridol prepared by above-described embodiment respectively and penfluridol ordinary tablet (commercially available) operates by Chinese Pharmacopoeia (2010 editions) second annex X A, its disintegration is checked.Result is as follows:

One, penfluridol ordinary tablet (commercially available)

Two, the oral freeze-dried compounded plate of penfluridol (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 Penfluridol Tablet quality standard and Chinese Pharmacopoeia (2010 editions) second annex X A, Penfluridol Tablet is no more than 15 minutes for qualified disintegration, actual measurement is 12 minutes, and the oral freeze-dried compounded plate of penfluridol (embodiment 1 and embodiment 2) disintegration is 6 minutes.It can thus be appreciated that penfluridol oral freeze-dried compounded plate disintegration is than reducing by 50% (6 minutes) Penfluridol Tablet (commercially available) disintegration, so penfluridol oral freeze-dried compounded plate absorption of human body is faster, the blood drug level peaking time is shorter than penfluridol 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 penfluridol oral freeze-dried slices, is characterized in that, is prepared from by following raw material:

2. a preparation method for penfluridol oral freeze-dried slices 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 4.5-5.5, 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 penfluridol 10 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;

Medicinal liquid is sub-packed in drug-containing dish after surveying penfluridol 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 the oral freeze-dried compounded plate of penfluridol.