A kind of pharmaceutical composition that contains Alendronate sodium
Technical field
The invention discloses a kind of pharmaceutical composition that is used to treat osteoporosis, particularly relate to a kind of pharmaceutical composition that contains the solid dispersion of Alendronate sodium.
Background technology
Alendronate sodium is a third generation diphosphate treatment osteoporosis.Alendronate sodium is new and effective bone resorption inhibitor, can suppress the activity of osteoclast, reduces bone resorption, directly is not suppressed to the active and bone formation process of osteocyte.Oral Alendronate sodium 10mg/ days or 70mg/ can suppress to reduce relevant bone loss with endogenous estrogen during week very effectively, and toleration is good, is a kind of Therapeutic Method of alternative postmenopausal osteoporosis newly.
The holdup time of Alendronate sodium intravenously administrable in blood is very short, and about 60%~70% concentrates in bone very soon, and remainder (30%~40%) is by RE.Behind the oral administration, the Alendronate sodium bioavailability is merely 0.7%.The main cause that produces is that Alendronate sodium can not can only pass through epithelial tight connection through the epithelial cell barrier through cell traffic, absorbs through paracellular shunt pathway and passes through.But its molecular weight is relatively large, has hindered this transhipment; In addition, under the small intestinal physiological pH, the complete ionization of Alendronate sodium, BBM institute is electronegative to have hindered them with the other approach transhipment of cell.Simultaneously Alendronate sodium has also reduced the oral administration biaavailability of Alendronate sodium with calcium ion and other bivalent cation complexations in small intestinal.
Alendronate sodium has certain stimulation to esophagus.Find that in clinical practice erosive esophagitis takes place the minority women, thus these article should not be used for esophagostenosis, relax can not or the patient of other esophagus emptying obstacles, to dyspepsia, the women Yao Shenyong of dysphagia or other gastroenteropathys.
The bioavailability that the Alendronate sodium oral formulations is extremely low makes most medicine fail fully to be absorbed by human body effectively, and excessive Alendronate sodium is the main cause that causes side effect to take place.So the zest of the dissolubility of increase medicine, the bioavailability that improves, minimizing mucosa becomes the subject matter of this medicine.
CN1745753A, two pieces of patents of CN1745754A disclose the preparation that adopts inclusion technique and the preparation of nanoscale principal agent respectively.Because the poorly water-soluble of Alendronate sodium, more than two pieces of patents do not mention the problems such as zest that improve bioavailability, minimizing mucosa through the dissolubility that adopts the method that prepare solid dispersion to improve principal agent.The applicant finds through a large amount of experiment, and the solid dispersion system that adopts Eudragit E100 and PEG6000 and Alendronate sodium to process efficiently solves the poorly soluble problem of principal agent, raising bioavailability of medicament, the toxic and side effects of reduction Alendronate sodium.
Summary of the invention
The present invention provides a kind of pharmaceutical composition that contains Alendronate sodium, contains the solid dispersion and the acceptable accessories of Alendronate sodium.
Pharmaceutical composition provided by the invention, described solid dispersion carrier are the mixture that Eudragit F100 and PEG6000 form.
Solid dispersion provided by the invention, the percentage by weight of said Eudragit E100 are 1%~15%.Solid dispersion according to claim 2 is characterized in that described PEG6000 percentage by weight is 5%~30%.
Pharmaceutical composition provided by the invention, described acceptable auxiliary are starch, microcrystalline Cellulose.
Pharmaceutical composition provided by the invention, the percentage by weight of said starch are 15%~35%.
Pharmaceutical composition provided by the invention, the percentage by weight of said microcrystalline Cellulose are 15%~30%.
Pharmaceutical composition provided by the invention, described pharmaceutical composition is used to treat osteoporosis.
The specific embodiment
Below in conjunction with embodiment the present invention is done further detailed description, but be not limited to following embodiment.Wherein " % " is meant " percentage by weight ".
Embodiment 1
This embodiment is for directly processing tablet
Preparation technology: take by weighing Alendronate sodium, PEG6000, Eudragit E100, microcrystalline Cellulose and starch mixing by recipe quantity, use 8% starch slurry solution to be binding agent, 16 order wet granulations, 60 ℃ of oven dry.24 order granulate are measured moisture, after adding magnesium stearate and Pulvis Talci mix, and 60~80N tabletting.
Embodiment 2
This embodiment processes sheet again after processing solid dispersion earlier
Preparation technology: take by weighing Alendronate sodium, PEG6000 by recipe quantity, Eudragit E100 prepares solid dispersion, behind the crushing screening with microcrystalline Cellulose, starch mixing; 16 order wet granulations; 60 ℃ of oven dry, 24 order granulate are measured moisture; After adding the mixing of magnesium stearate and Pulvis Talci, 60~80N tabletting.
Embodiment 3
This embodiment processes sheet again after processing solid dispersion earlier
Preparation technology: take by weighing Alendronate sodium, PEG6000, Eudragit E100 by recipe quantity and prepare solid dispersion, with microcrystalline Cellulose, starch and mixing, use 8% starch slurry solution to be binding agent behind the crushing screening; 16 order wet granulations; 60 ℃ of oven dry, 24 order granulate are measured moisture; After adding the mixing of magnesium stearate and Pulvis Talci, 60~80N tabletting.
Embodiment 1, embodiment 2 and embodiment 3 are carried out drug release determination.
Assay method: according to the assay method of release degree, promptly " 2005 editions two appendix XD drug release determinations of the Chinese pharmacopoeia method three therapeutic methods of traditional Chinese medicine is a release medium with 250mL water, temperature (37.5 ± 0.5) ℃, 75 rev/mins of rotating speeds.The result sees the following form:
Process solid dispersion through this pharmaceutical composition, increase the dissolution rate of principal agent, bioavailability of medicament improves, and reduces toxic and side effects.