CN102784119A - Roxithromycin composition freeze-dried orally disintegrating tablets and preparation method thereof - Google Patents

Abstract

The invention provides roxithromycin composition freeze-dried orally disintegrating tablets and a preparation method of the orally disintegrating tablets, relates to the field of a medicine and a medicine preparation method technology and mainly solves the problems in the prior art that the oral preparation made by roxithromycin is not suitable for children, old people, bedridden patients, patients suffering from serious disability and the patients who are difficult to swallow. The roxithromycin composition freeze-dried orally disintegrating tablets are prepared from the following components by weight: 30-66% of roxithromycin, 33-66% of mannitol, 2-4% of gelatin, 0.1-0.15% of trichlorosucrose and 50-70% of tertiary butanol-water. The roxithromycin composition freeze-dried orally disintegrating tablets prepared by the above components are easy in preparation process, and simple in components, and mainly meet the administration requirements of children, old people, bedridden patients, patients suffering from serious disability and the patients who are difficult to swallow; moreover, the roxithromycin composition freeze-dried orally disintegrating tablets have the advantages of being fast to disintegrate, convenient to take, and good in taste; and the tablets take effect quickly and are fully absorbed, and the first pass effect of the liver is avoided.

Description

Roxithromycin composition freeze-drying oral cavity disintegration tablet and preparation method thereof

Technical field:

The present invention relates to the method for preparing technical field of medicine and medicine, relate in particular to a kind of Roxithromycin composition freeze-drying oral cavity disintegration tablet and preparation method thereof.

Background technology:

The Roxithromycin outward appearance is white or off-white color crystalline powder, and pH is 8.0-10.0.These article are macrolide antibiotics, are white or off-white color crystalline powder, and odorless, bitter in the mouth slightly draw moist.Be soluble in ethanol, the tert-butyl alcohol and acetone, dissolve in methanol and the ether, almost insoluble in the water; Roxithromycin antimicrobial spectrum and erythromycin are close; To staphylococcus aureus (except the MRsA), streptococcus (comprise streptococcus pneumoniae and A, B, C type streptococcus, but except G type and the enterococcus), corynebacterium, Lee department make a mistake bacterium, mucositis mora bacterium (micrococcus catarrhalis), the legionella equal altitudes is responsive or responsive.To bacteroides oralis, produce anaerobe such as black bacteroid, dyspepsiacoccus, peptostreptococcus, propionibacterium acnes and encephalitis toxoplasma, chlamydia, treponema pallidum etc. antibacterial action preferably also arranged, a little less than effects such as pylori, gonococcus, meningococcus, bordetella pertussis.

The Roxithromycin structural formula is following:

The Roxithromycin dosage form of listing is mainly conventional tablet, dispersible tablet, capsule, slow releasing tablet at present.

The Roxithromycin preparation of these dosage forms to tumor patient, child, old age, be unable to leave the bed and the severely-disabled patient suitable, can't administration to swallowing inconvenient patient.

The characteristics of the preparation of oral cavity disintegration tablet are: do not need water or only need a small amount of water, also need not to chew, medicine places in the oral cavity, after rapid dissolving of chance saliva or the disintegrate, along with autonomous and involuntary swallowing act entering digestive system absorption back onset of user.Behavior is basic consistent with conventional tablet in the body.Different with sublingual lozenge, onset does not also rely on oral mucosa and absorbs, the novel dosage form of this kind to tumor patient, child, old age, be unable to leave the bed and severely-disabled patient's optimum, and route of administration is provided to swallowing inconvenient patient.

Because the Roxithromycin bitter in the mouth is insoluble in water, therefore be difficult to be formed in buccal tablet and the oral cavity disintegration tablet that keeps certain hour in the oral cavity.In the prior art, the disintegration rate of oral cavity disintegration tablet is slow.

So still lack at present and press for a kind of like this Roxithromycin preparation, its preparation technology is simple, component is simple.The oral absorption rate is high, and taking convenience, delicious is specially adapted to child, old age, is unable to leave the bed, the severely-disabled patient, and to swallowing inconvenient patient's medication.

Summary of the invention:

Technical problem to be solved by this invention is to provide a kind of composition simple, easily manufactured, rapid-action Roxithromycin compositions and contain Roxithromycin composition freeze-drying oral cavity disintegration tablet that above-mentioned composition processes and preparation method thereof.

Technical problem to be solved by this invention adopts following technical scheme to realize.

A kind of Roxithromycin compositions, the prescription of said composition is made up of principal agent and accessory drugs, it is characterized in that: principal agent is a Roxithromycin, accessory drugs be chosen as skeleton agent (mannitol), forming agent (gelatin), correctives (sucralose).

A kind of Roxithromycin compositions is characterized in that, said composition comprises following component and component quantity ratio:

The preferred ingredient quantity ratio of said each component of Roxithromycin compositions is:

Another object of the present invention provides a kind of Roxithromycin composition freeze-drying oral cavity disintegration tablet that contains above-mentioned Roxithromycin compositions.This freeze-dry orally disintegrating tablet component is simple, need not water when taking, and need not to chew, and disintegration time was no more than for 2 seconds in human oral cavity; Rapid-action, intestinal is residual few, and liver first-pass effect is little, absorbs fully; Side effect is low, and mouthfeel is good, is particularly suitable for the infant patient and takes.

A kind of Roxithromycin composition freeze-drying oral cavity disintegration tablet that contains above-mentioned Roxithromycin compositions is prepared from following component and component quantity ratio:

The preferred ingredient quantity ratio of each component of preparation Roxithromycin composition freeze-drying oral cavity disintegration tablet is:

A further object of the present invention provides a kind of method for preparing of Roxithromycin composition freeze-drying oral cavity disintegration tablet; This method for preparing with the tertiary butanol and water cosolvent as solvent; Can accelerate the rate of sublimation of medicine, shorten lyophilization cycle, increase the Roxithromycin dissolving; Strengthen medicine stability, promote the crystallization of medicine.

For realizing a further object of the present invention, a kind of method for preparing of Roxithromycin composition freeze-drying oral cavity disintegration tablet is provided, adopt following technical scheme:

A) Roxithromycin with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;

B) mannitol, the sucralose with recipe quantity is dissolved in the water for injection of prescription with water for injection total amount 70%-80%, preparation solution b;

C) again the gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;

D) merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃;

E) mix a, two kinds of solution of d, and stir, regulate pH value to 8.0-10.0 with sodium bicarbonate;

F) according to Roxithromycin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%;

G) treat Roxithromycin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;

H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.

Said Roxithromycin composition freeze-drying oral cavity disintegration tablet specification is 150mg/ sheet, 250mg/ sheet or 300mg.

We have formulated relevant detection method to the disintegration rate of Roxithromycin composition freeze-drying oral cavity disintegration tablet:

Disintegration

According to inspection technique disintegration (two appendix ⅹ of Chinese Pharmacopoeia version in 2010 A); The stainless steel shaft of hanging basket through the upper end hung on the metal rack; Immerse in the 1000ml beaker; And screen cloth fills temperature and is 37 ℃ ± 1 ℃ water apart from beaker bottom 25mm in the beaker when regulating the hanging basket position it being descended, when regulating height of water level hanging basket being risen screen cloth in the underwater 15mm place.

Except as otherwise herein provided, get 4 groups of test samples (every group of dosage is 150mg), put respectively in the glass tubing of above-mentioned hanging basket, add baffle plate, start disintegration tester and check, each sheet all should all disintegrates in 1.2 seconds.Result such as following table:

Dosage equates, the disintegration time and the medicine of different Roxithromycin tablets reach peak concentration

As stated above to Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention and Roxithromycin ordinary tablet comparative determination; The present invention is up to specification; The Roxithromycin ordinary tablet disintegration can not be qualified, and the disintegration rate of Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention is far longer than the Roxithromycin ordinary tablet.

The selected adjuvant of Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention all is the adjuvants that are suitable for this tablet of preparation.Discover according to us; The water solublity of Roxithromycin is very poor, and we adopt the tertiary butanol and water cosolvent as solvent in technology, is insoluble in the Roxithromycin of water with tert-butyl alcohol dissolving; With other adjuvants of water for injection dissolving; Both mix with suitable ratio then, are dissolved the clear and bright cosolvent of water solublity and liposoluble substance jointly, use this technology to have multiple advantage.

The first, because the freezing point of the tert-butyl alcohol is high; Just can freeze at normal temperatures; With also can just can solidify after who mixes in the subzero several years, and tert-butyl alcohol vapour pressure is high, the vapour pressure height helps distillation; So use the tertiary butanol and water cosolvent can shorten freeze-drying time as solvent, the obtained freeze-drying product still keeps porous simultaneously.

The second, the tert-butyl alcohol and water can be with any mixed, and the medicine with slightly water-soluble is dissolved in the tert-butyl alcohol like this, can strengthen stability of drug.

Three, the adding of the tert-butyl alcohol can change the crystalline state of water, and then the drug crystallization state that is dissolved in the water is changed, and improves freezing point, and rate of sublimation improves greatly.

Four, tert-butyl alcohol toxicity is low, and after the lyophilizing almost there is not residual quantity, and this has just guaranteed the safety of drug use.

Since Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention mainly in order to satisfy child's medication demand, and the Roxithromycin taste is pungent, for improving the compliance of children, in prescription, has added the correctives sucralose.In traditional production application, aspartame flavour mouthfeel is pretty good, but is prone to decompose instability; Cyclamate, glucide safety receive dispute to a certain degree, and are prone to produce the back bitterness.And the sucralose sweet feel is very near sucrose, and is very stable, safe to heat, acid, alkali.Simultaneously, sucralose is not utilized by the dental caries pathogenic bacteria, can reduce pathogenic bacteria in the oral cavity, and the acid amount of generation and streptococcus cell effectively play the dental caries effect in the adhesion of dental surface, and useful especially teenager teeth is healthy; The sucralose good stability can long term storage, and in freezing dry process, can not be damaged, and is fit to industrial applications.

The present invention has following beneficial effect:

The first, disintegrate is rapid, and drug effect is fast.Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate rapidly in 2 seconds in mouth, is beneficial to the rapid stripping of medicine, shortens dissolution time, accelerates to absorb, and liver first-pass effect is little, makes its performance curative effect fast.

The second, drug absorption is abundant.Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention is disintegrate fully in the oral cavity, makes the absorption of medicine more abundant, helps improving bioavailability of medicament like this.

Three, taking convenience, mouthfeel is good.Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention needn't be used water delivery service, and saliva can make its complete disintegrate, and no foreign body sensation in mouthful is owing to wherein add the compliance that the sweet child of helping of suitable correctives cool taste flavor takes medicine.Compare with liquid preparation and dosage advantage accurately arranged.

Four, avoid the first pass effect of liver, because Roxithromycin composition freeze-drying oral cavity disintegration tablet of the present invention disintegrate rapidly in mouth except that major part gets into the gastrointestinal tract with swallowing act, also has the considerable part trans-oral to absorb, thereby rapid-action, first pass effect is little.

The specific embodiment:

For technological means, creation characteristic that the present invention is realized, reach purpose and effect and be easy to understand and understand, below in conjunction with specific embodiment, further set forth the present invention.

Embodiment 1

With the 250mg/ sheet is that example prepares Roxithromycin composition freeze-drying oral cavity disintegration tablet

Prescription: 1000 amounts

Preparation technology:

The Roxithromycin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 8.0-10.0 with sodium bicarbonate; According to Roxithromycin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating Roxithromycin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.

Embodiment 2

With the 250mg/ sheet is that example prepares Roxithromycin composition freeze-drying oral cavity disintegration tablet

Prescription: 1000 amounts

Preparation technology:

The Roxithromycin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 8.0-10.0 with sodium bicarbonate; According to Roxithromycin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating Roxithromycin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.

Embodiment 3

With the 250mg/ sheet is that example prepares Roxithromycin composition freeze-drying oral cavity disintegration tablet

Prescription: 1000 amounts

Preparation technology:

The Roxithromycin of recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a; Mannitol, the sucralose of recipe quantity are dissolved in the water for injection of prescription with water for injection total amount 70%-80% preparation solution b; Gelatin with recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30% again, is heated to dissolving fully, preparation solution c; Merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃; Mix a, two kinds of solution of d, and stir, regulate pH value to 8.0-10.0 with sodium bicarbonate; According to Roxithromycin composition freeze-drying oral cavity disintegration tablet specification; After confirming loading amount, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and put into freeze drying box; Medicinal liquid is carried out freezing (cryogenic temperature is-20 ℃--50 ℃); Evacuation dry (baking temperature is at+0 ℃-+5 ℃, vacuum be-more than the 0.09MPa) is controlled moisture and is no more than 1.0%; After treating Roxithromycin composition freeze-drying oral cavity disintegration tablet drying, in freeze drying box, seal; Cut drug-containing dish after the medicament that freezes taken out freeze drying box, and carry out finished product packing.

More than show and described 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; That describes in the foregoing description and the description is merely preference of the present invention, is not used for limiting the present invention, under the prerequisite that does not break away from spirit and scope of the invention; The present invention also has various changes and modifications, and these variations and improvement all fall in the scope of the invention that requires protection.The present invention requires protection domain to be defined by appending claims and equivalent thereof.

Claims (6)

1. a Roxithromycin compositions is characterized in that, said composition comprises following component and component quantity ratio:

2. Roxithromycin compositions according to claim 1 is characterized in that, the preferred ingredient quantity ratio of said each component of Roxithromycin compositions is:

3. a Roxithromycin composition freeze-drying oral cavity disintegration tablet that contains the said compositions of claim 1 is characterized in that, is prepared from following component and component quantity ratio:

4. Roxithromycin composition freeze-drying oral cavity disintegration tablet according to claim 3 is characterized in that, the preferred ingredient quantity ratio of each component of preparation Roxithromycin composition freeze-drying oral cavity disintegration tablet is:

5. the method for preparing of the said Roxithromycin composition freeze-drying of claim 3 oral cavity disintegration tablet is characterized in that the concrete steps of this method for preparing are:

A) Roxithromycin with recipe quantity is dissolved in the tert-butyl alcohol of recipe quantity, and stirring and dissolving continues to stir at normal temperatures, preparation solution a;

B) mannitol, the sucralose with recipe quantity is dissolved in the water for injection of prescription with water for injection total amount 70%-80%, preparation solution b;

C) again the gelatin of recipe quantity is dissolved in the water for injection of prescription water consumption 20%-30%, is heated to dissolving fully, preparation solution c;

D) merge above-mentioned b, two kinds of solution of c become solution d, and stir, mixed then solution is cooled to below 5 ℃;

E) mix a, two kinds of solution of d, and stir, regulate pH value to 8.0-10.0 with sodium bicarbonate;

F) according to Roxithromycin composition freeze-drying oral cavity disintegration tablet specification, confirm loading amount after, the medicinal liquid after merging is moved in the drug-containing dish by loading amount, and puts into freeze drying box, to medicinal liquid carry out freezing, evacuation is dry, the control moisture is no more than 1.0%;

G) treat Roxithromycin composition freeze-drying oral cavity disintegration tablet drying after, in freeze drying box, seal;

H) cut drug-containing dish after the medicament that freezes is taken out freeze drying box, and carry out finished product packing.

6. the method for preparing of Roxithromycin composition freeze-drying oral cavity disintegration tablet according to claim 5 is characterized in that: said Roxithromycin composition freeze-drying oral cavity disintegration tablet specification is 150mg/ sheet, 250mg/ sheet or 300mg.