Drug – bio-affecting and body treating compositions – Solid synthetic organic polymer as designated organic active... – Polymer from ethylenic monomers only
Patent
1987-11-10
1989-09-26
Schofer, Joseph L.
Drug, bio-affecting and body treating compositions
Solid synthetic organic polymer as designated organic active...
Polymer from ethylenic monomers only
424 80, A61K 3174
Patent
active
048698997
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a pharmaceutical composition containing nifedipine as the active constituent and to a process for the preparation of a sublingual dosable adminstrable pharmaceutical composition with nifedipine as the active constituent.
Nifedipine is an established therapeutical agent for coronary heart disease and solid formulations containing nifedipine together with processes for their manufacture have become common knowledge, for example through DE-OS 28 22 882. Nifedipine: 4-(2-nitrophenyl)-2,6-dimethyl-3,5-dicarboxymethoxy-1,4-dihydropyridine is known to be extremely light-sensitive and there have been a number of suggestions for administering this compound so as to prevent photo-decomposition and the associated reduction in efficacy. DE-OS 28 22 882 discloses a formulation in which solid nifedipine is mixed with polyvinylpyrrolidine, methyl cellulose, hydroxypropyl cellulose and hydroxypropylmethyl cellulose, accompanied by additional surfactants, in particular oils. This method of application was chosen in the first instance in order to improve the bioavailability of the drug following administration but is nevertheless associated with considerable disadvantages in terms of stability and photosensitivity. For oral administration, capsules have been suggested as an alternative to tablets/pills, with incorporation of dyes into the capsule shells in order to overcome photo-degradation. Such a composition is exemplified in DE-PS 22 09 526 in which the dye yellow-orange S 15985 was selected for incorporation into the capsule shell together with an opacifier. As a rule such capsule shells are sensitive to temperature-changes and in this particular case also, complete stability against decomposition of the active constituent cannot be guaranteed.
Liquid formulations containing dihydropyridines are exemplfied in DE-OS 33 07 422. Such liquid pharmaceutical preparations containing nifedipine, although showing a relatively rapid onset of action following sublingual administration, produce only relatively low plasma-concentrations in the phase immediately following administration.
A comparison of the modes of action of nifedipine after oral and sublingual application is to be found in, "Nifedipine serum concentrations following sublingual and oral doses" (Brown et al, International Journal of Clinical Pharmacology, Therapy and Toxicology, Vol. 24, No. 6, 1986, pp 283-286). According to this paper, it was observed that oral administration leads to higher maximum plasma levels and therefore to a very good effect, whereas sublingual administration is characterized by a rapid onset of action with reduced maximum plasma levels. These differences in effect are attributed to the fact that upon sublingual administration, there is an initial precipitation of nifedipine crystals in the saliva such that only a portion of the nifedipine applied is absorbed, whilst the remaining portion, which has precipitated as crystals, dissolves and reaches the circulation at a later time.
An object of the present invention, therefore, is to produce a pharmaceutical composition containing nifedipine which, when compared with known presentations, is distinguished by a more rapid sublingual absorption and a high plasma-concentration in short time after sublingual adminstration. The compositions of the present invention should possess a high degree of stability and are suitable for rapid and unrestricted administration in the absence of medical assistance.
In order to achieve this, the invented pharmaceutical preparation comprises a solution of the active drug together with polyalcohols, such as polyethylene and/or polyalkyleneglycols and/or polyethylene glycol alkyl phenyl ethers and/or polyglycerine fatty acid esters and/or glycerine-polyethyleneglycol oxyfatty acid esters such as glycerine-polyethyleneglycol oxyoleate and/or glycerine-polyethyleneglycoloxystearate and/or partial fatty acid esters of sorbitol or polyhydroxyethylene sorbitol and/or polyvinylalcohols and/or polyhydroxyethylene aliphatic acid esters of pol
REFERENCES:
patent: 4442112 (1984-04-01), Muller-Schweinitzer
Wu Bai Ming, et al, "Rapid Antihypertension Effects of Nifedipine Spray", Chinese Journal of Cardiovascular Diseases, 1980, vol. 8, No. 3, pp. 1-9.
G. R. Brown et al, "Nifedipine Serum Concentrations Following Sublingual and Oral Doses", Int'l Journal of Clinical Pharmacology, Therapy and Toxicology, vol. 24, No. 6-1986 (pp. 283-286).
Burghart Kurt
Burghart Walter
Pili-Curtis Carmen
Schofer Joseph L.
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