Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Matrices
Reexamination Certificate
2000-08-01
2003-05-13
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Matrices
C424S464000, C424S465000, C424S482000
Reexamination Certificate
active
06562375
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a solid pharmaceutical composition for oral use with that prevents changes in drug release in a matrix type sustained-release preparation containing polyethylene oxide. The present invention also relates to a method of producing a stable solid pharmaceutical composition for oral use that prevents changes in drug release in a matrix type sustained-release preparation containing polyethylene oxide. Furthermore, the present invention relates to a method of preventing changes in drug release in a matrix type sustained-release preparation containing polyethylene oxide.
BACKGROUND OF THE INVENTION
Various sustained-release preparations have been developed in the field of pharmaceuticals, and release of the drug from this preparation is an important factor of preparation design in terms of in vivo absorption of the drug when the preparation is orally taken by the patient. Stable drug release from the preparation, wherein the release rate is steady with few changes, is essential, from the time the pharmaceutical preparation is made until it is transported, stored and orally taken by the patient.
Incidentally, various sustained-release preparations have been made by researchers affiliated with the applicant of the present patent. It goes without saying that, as with the main agent, in sustained-release preparations, the polymer substance that forms a hydrogel as the main base in particular must be also stable in order to maintain the rate with which the drug is released (WO 94/06414).
Polyethylene oxide can be mentioned as one polymer substance that forms a hydrogel. This substance is a water-soluble thermoplastic resin in the form of white powder or granules that is obtained by polymerization of ethylene oxide and that has a molecular weight of from several 100,000s to several 1,000,000s. It is known that because it is extremely sticky when wet, sustained-release preparations containing this substance show good drug release within the digestive tract. Although it is a known fact that the erosion rate of the polymer substance or a matrix made from said substance has a strong effect on this drug release rate, the factors that affect stability of the polyethylene oxide that is used as the base of sustained-release preparations, particularly factors that affect drug release, are not known.
The present inventors performed studies of polyethylene oxide as the base of sustained-release preparations, and they discovered that erosion of the matrix made from polyethylene oxide is accelerated when the preparation is preserved under exposure to light. As a result, the rate with which the drug is released increases over time, and there are changes in drug release. Therefore, the prevention of changes in drug release is desired.
DISCLOSURE OF THE INVENTION
The present invention provides a stable preparation that shows no changes in drug release in matrix type sustained-release preparations containing polyethylene oxide at the preserved period under exposure to light. Moreover, the present invention provides a method of producing a stable preparation with which there are no changes in drug release in matrix type sustained-release preparations containing polyethylene oxide. The present invention further provides a method with which changes in drug release are prevented in matrix type sustained-release preparations containing drugs and polyethylene oxide at the preserved period under exposure to light.
Under the above circumstances, the present inventors discovered that changes in drug release can be prevented at the preserved period even under exposure to light, if yellow ferric oxide or red ferric oxide, which has been used as coloring agent among pharmaceutical additives, was added by physical mixing in an amount of 10 wt %, which is in excess of the amount used as coloring agent (which said amount is very small and not more than 0.1 wt %) with drug and polyethylene oxide in a matrix type sustained-release preparation containing polyethylene oxide and was made into a tablet. The present inventors completed the present invention upon discovering that changes in drug release from a preparation can be prevented by adding yellow ferric oxide or red ferric oxide not only by means of physical mixing, but also by means of coating a tablet.
The mechanism of preventing effect by adding yellow ferric oxide or red ferric oxide has not been discerned, but it is thought that the mechanism is not just a prevention of the degradation of polyethylene oxide by exposure to light. That is, the present inventors found that titanium oxide absorbing light at the wavelength of not more than 400 nm (UV) and reflecting light at the wavelength of not less than 400 nm, or medicinal carbon absorbing light at all wavelength (broad range) cannot reduce changes in drug release in a matrix type tablet consisting of polyethylene oxide and polyethylene glycol even if it was added by physical mixing in an amount of 10 wt %, for example, per tablet weight. The anticipation that the stability against light can be performed if the wavelength (color) affecting the influence on the stability of polyethylene oxide is blocked. To the contrary, changes in drug release on the tablet could not be reduced even if all visual light was blocked by reflecting or by absorbing. This result suggested that the special wavelength affecting the influence on the stability in the visual region did not exist because the color of solution dissolving polyethylene oxide was colorless and clear. It had no absorbed wavelength in the visual region. If the special wavelength affecting the influence on the stability in visual region existed, the additive reflecting all visual light (white color) or the additive absorbing all visual light (black color) was anticipated to be able to make the stable preparation with no changes in drug release. To the contrary, it was an unexpected result. Therefore, although there is/are unknown factor(s) affecting changes in drug release besides light, the results suggested that yellow ferric oxide, which absorbs light at wavelength of not more than 400 nm and reflects light at wavelength of not less than 400 nm, or red ferric oxide, which absorbs light at wavelength of not more than 560 nm and reflects light at wavelength of not less than 560 run, could be added in an effective amount in a matrix type sustained-release preparation containing at least polyethylene oxide can reduce changes in drug release although the factor(s) affecting changes in drug release by compounding, by physical mixing or by coating tablet, may exist.
Accordingly, the present invention relates to 1) a stable pharmaceutical composition for oral use comprising a yellow ferric oxide and/or a red ferric oxide in an effective amount to stabilize a matrix type sustained-release preparation containing a drug, hydrophilic base, and polyethylene oxide. Moreover, the present invention relates to 2) the stable pharmaceutical composition for oral use according to the above-mentioned 1), wherein the amount of yellow ferric oxide and/or red ferric oxide added is not less than 0.3 wt % per tablet weight. The present invention also relates to 3) the stable pharmaceutical composition for oral use according to the above-mentioned 1) or 2), wherein the amount of yellow ferric oxide added is present from 1 to 20 wt % per preparation weight. In addition, the present invention relates to 4) the stable pharmaceutical composition for oral use according to the above-mentioned 1) or 2), wherein the amount of red ferric oxide added is present from 5 to 20 wt % per preparation weight. The present invention relates to 5) a method of producing a stable pharmaceutical composition for oral use comprising adding yellow ferric oxide and/or red ferric oxide in an amount effective to stabilize a matrix type sustained-release preparation to a mixture drug, hydrophilic base, and polyethylene oxide. Moreover, the present invention relates to 6) the method of producing a stable pharmaceutical composition for oral use according to the above-mention
Sako Kazuhiro
Sawada Toyohiro
Watanabe Shunsuke
Yoshihara Keiichi
Yoshioka Tatsunobu
Joynes Robert M.
Page Thurman K.
Townsend and Townsend / and Crew LLP
Yamanouchi Pharmaceuticals Co., Ltd.
LandOfFree
Stable pharmaceutical composition for oral use does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Stable pharmaceutical composition for oral use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stable pharmaceutical composition for oral use will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3019617